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Parkinson's Disease: Diagnosis and Treatment

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... of this page please turn JavaScript on. Feature: Parkinson's Disease Parkinson's Disease: Diagnosis and Treatment Past Issues / Winter 2014 Table of Contents Medications for Parkinson's disease can help many patients live productive lives and ...

Laughter Yoga, Adults Living With Parkinson׳s Disease, and Caregivers: A Pilot Study.

PubMed

DeCaro, Debra Swedberg; Constantine Brown, Jodi L

2016-01-01

This study explored outcomes of Laughter Yoga in adults with Parkinson׳s disease (PD) and their caregivers. Laughter has been shown to generally improve mood in physically healthy adults, and specifically in adults with heart disease or cancer, but little research exists regarding the impact of laughter in adults with Parkinson׳s disease. Low mood is frequently a co-morbid condition for adults with Parkinson׳s disease, and can negatively affect their caregivers. Pre-experimental (O1 × O2) pretest-posttest design. Data collection occurred at six unique PD support groups in Southern California. Participants (N = 85) comprised a convenience sample of adults diagnosed with Parkinson׳s disease (n = 47) and accompanying caregivers (n = 38). Subjects participated in a 45-min Laughter Yoga (LY) session conducted by a Certified Laughter Yoga Teacher. This study utilized the Laughter Yoga "How Do You Feel?" (HDYF) form. The form consists of a series of 10 scales labeled "well-being" measures including enthusiasm, energy level, mood, optimism, stress level, level of friendship with group members, level of awareness about breathing, level of muscle relaxation, level of mental relaxation, and ability to laugh without a reason. Paired sample t-tests reveal statistically significant improvements in well-being for adults with PD and their caregivers after attending an LY session. Therapists and other clinicians should consider utilizing this unique technique with adults with PD to address co-morbid low-mood conditions and include caregivers in the LY sessions for support and their own benefit. Copyright © 2016 Elsevier Inc. All rights reserved.

Combined Diffusion Tensor Imaging and Apparent Transverse Relaxation Rate Differentiate Parkinson Disease and Atypical Parkinsonism.

PubMed

Du, G; Lewis, M M; Kanekar, S; Sterling, N W; He, L; Kong, L; Li, R; Huang, X

2017-05-01

Both diffusion tensor imaging and the apparent transverse relaxation rate have shown promise in differentiating Parkinson disease from atypical parkinsonism (particularly multiple system atrophy and progressive supranuclear palsy). The objective of the study was to assess the ability of DTI, the apparent transverse relaxation rate, and their combination for differentiating Parkinson disease, multiple system atrophy, progressive supranuclear palsy, and controls. A total of 106 subjects (36 controls, 35 patients with Parkinson disease, 16 with multiple system atrophy, and 19 with progressive supranuclear palsy) were included. DTI and the apparent transverse relaxation rate measures from the striatal, midbrain, limbic, and cerebellar regions were obtained and compared among groups. The discrimination performance of DTI and the apparent transverse relaxation rate among groups was assessed by using Elastic-Net machine learning and receiver operating characteristic curve analysis. Compared with controls, patients with Parkinson disease showed significant apparent transverse relaxation rate differences in the red nucleus. Compared to those with Parkinson disease, patients with both multiple system atrophy and progressive supranuclear palsy showed more widespread changes, extending from the midbrain to striatal and cerebellar structures. The pattern of changes, however, was different between the 2 groups. For instance, patients with multiple system atrophy showed decreased fractional anisotropy and an increased apparent transverse relaxation rate in the subthalamic nucleus, whereas patients with progressive supranuclear palsy showed an increased mean diffusivity in the hippocampus. Combined, DTI and the apparent transverse relaxation rate were significantly better than DTI or the apparent transverse relaxation rate alone in separating controls from those with Parkinson disease/multiple system atrophy/progressive supranuclear palsy; controls from those with Parkinson

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.

Hereditary Parkinson s Disease Natural History Protocol

ClinicalTrials.gov

2018-03-27

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

Can loss of the swallow tail sign help distinguish between Parkinson Disease and the Parkinson-Plus syndromes?

PubMed

Oustwani, Christopher Sami; Korutz, Alexander William; Lester, Malisa Siri; Kianirad, Yasaman; Simuni, Tanya; Hijaz, Tarek Aref

To determine if loss of the swallow tail sign (STS) can distinguish Parkinson Disease (PD) from the Parkinson-Plus syndromes. Twenty-five patients with PD, 21 with Parkinson-Plus syndromes, and 14 control patients were included. Presence of the STS was assessed. The STS was present in 79% of controls, statistically greater than the PD/Parkinson-Plus patients. There was no difference in the presence of the STS between the PD/Parkinson-Plus subgroups or when scanning at 1.5 T or 3 T. Loss of the STS could not distinguish between PD and Parkinson-Plus patients. The STS can be identified at both 1.5 T and 3 T. Copyright © 2017 Elsevier Inc. All rights reserved.

Nursing interventions for rehabilitation in Parkinson's disease: cross mapping of terms.

PubMed

Tosin, Michelle Hyczy de Siqueira; Campos, Débora Moraes; Andrade, Leonardo Tadeu de; Oliveira, Beatriz Guitton Renaud Baptista de; Santana, Rosimere Ferreira

2016-08-08

com a taxonomia e o refinamento feito pelos especialistas, resultaram em 32 intervenções equivalentes ao sistema de Classificação das Intervenções de Enfermagem. "Ensino: Processo da doença", "Contrato com o Paciente" e "Facilitação da Aprendizagem" estiveram presentes em 100% dos prontuários. Para essas, foram descritas 40 atividades, representando 13 atividades por intervenção prescrita. o mapeamento cruzado permitiu levantar os termos correspondentes às Intervenções de Enfermagem utilizados no cotidiano dos enfermeiros de reabilitação e compará-los ao sistema de Classificação das Intervenções de Enfermagem. realizar el mapeo cruzado de términos del lenguaje de Enfermería con el Sistema de Clasificación de las Intervenciones de Enfermería en historias clínicas de pacientes con enfermedad de Parkinson en rehabilitación. estudio de investigación documental para realización de mapeo cruzado. Muestra probabilística de tipo aleatoria simple, compuesta por 67 historias clínicas de pacientes con enfermedad de Parkinson que participaron del programa de rehabilitación entre marzo de 2009 y abril de 2013. Investigación realizada en tres etapas donde fueron mapeados los términos de Enfermería en lenguaje libre y cruzados con el sistemas de Clasificación de Intervenciones de Enfermería. se identificaron 1077 intervenciones normalizadas que, después del cruzamiento con la taxonomía y el refinamiento hecho por los especialistas, resultaron en 32 intervenciones equivalentes al sistema de Clasificación de Intervenciones de Enfermería. "Enseñanza: Proceso de la enfermedad", "Contrato con el paciente" y "Facilitación del aprendizaje" estuvieron presentes en 100% de las historias clínicas. Para éstas, se describieron 40 actividades, representando 13 actividades por cada intervención prescripta. el mapeo cruzado permitió encontrar los términos correspondientes a las Intervenciones en Enfermería utilizados en el día a día de los

Molecular imaging to track Parkinson's disease and atypical parkinsonisms: New imaging frontiers.

PubMed

Strafella, Antonio P; Bohnen, Nicolaas I; Perlmutter, Joel S; Eidelberg, David; Pavese, Nicola; Van Eimeren, Thilo; Piccini, Paola; Politis, Marios; Thobois, Stephane; Ceravolo, Roberto; Higuchi, Makoto; Kaasinen, Valtteri; Masellis, Mario; Peralta, M Cecilia; Obeso, Ignacio; Pineda-Pardo, Jose Ángel; Cilia, Roberto; Ballanger, Benedicte; Niethammer, Martin; Stoessl, Jon A

2017-02-01

Molecular imaging has proven to be a powerful tool for investigation of parkinsonian disorders. One current challenge is to identify biomarkers of early changes that may predict the clinical trajectory of parkinsonian disorders. Exciting new tracer developments hold the potential for in vivo markers of underlying pathology. Herein, we provide an overview of molecular imaging advances and how these approaches help us to understand PD and atypical parkinsonisms. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Prevalence of parkinsonism and Parkinson's disease in the Arosa Island (Spain): a community-based door-to-door survey.

PubMed

Seijo-Martinez, M; Castro del Rio, M; Rodríguez Alvarez, J; Suarez Prado, R; Torres Salgado, E; Paz Esquete, J; Sobrido, M J

2011-05-15

There are scarce epidemiological data on parkinsonism in Spain. Since the Arosa Island community (Northwestern Spain) has been for centuries relatively isolated, it represents a potentially useful setting to undercover genetic factors with a founder effect, as well as local environmental influences. We performed a one-stage door-to-door survey in the Arosa Island in 2004 to determine the prevalence of parkinsonism and Parkinson's disease (PD) in the population aged 65 years or over. Out of 41 individuals detected with parkinsonism, 15 were diagnosed with PD (36.6%), 13 with drug induced parkinsonism (31.7%), seven with vascular parkinsonism (17.1%), four patients had parkinsonism with associated features (9.8%) and two had unspecified parkinsonism (4.9%). We obtained a crude prevalence rate of parkinsonism of 5.44% (adjusted rate: 4.73%) and a crude prevalence rate of PD of 1.99% (adjusted rate 1.7%); both prevalence rates increased with advancing age. The prevalence rate for parkinsonism was higher than that in similar populations of Spain and other European countries while that for PD was in the range obtained from these populations. Among PD cases, 26.7% (n=4) were undiagnosed before the survey. Most cases of drug-induced parkinsonism were secondary to neuroleptics and had not been previously diagnosed. The relatively high proportion of undiagnosed drug-induced parkinsonisms and PD is surprising in a public health system which is free and universal. The lack of excess of late-onset PD among Arosans does not support the existence of specific genetic or environmental factors contributing to PD in this particular geographical area. Copyright © 2011 Elsevier B.V. All rights reserved.

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

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.

Electroconvulsive Therapy Intervention for Parkinson's Disease.

PubMed

Narang, Puneet; Glowacki, Anna; Lippmann, Steven

2015-01-01

Electroconvulsive therapy is an established means to improve function in a variety of psychiatric and neurologic conditions, particularly for patients who remain treatment-refractory. Parkinson's disease is a neurodegenerative disorder that sometimes does not respond well to conventional pharmacotherapies. Reports have indicated that electroconvulsive therapy may be an effective and safe treatment for those patients with Parkinson's disease who are not optimally responding to first-line treatments. Despite these reports, however, electroconvulsive therapy is not often used by clinicians in patients with treatment-resistant Parkinson's disease, perhaps due to stigma, lack of knowledge regarding its safety and efficacy, and/or inability to predict the duration of therapeutic benefit. Our objective was to determine if the available literature on ECT supports it as a safe and effective treatment option in patients with treatment-refractory Parkinson's disease. Motoric improvement induced by electroconvulsive therapy has been documented for decades in persons with Parkinson's disease. Efficacy and safety are reported following electroconvulsive therapy in people with Parkinson's disease who have sub-optimal response to medicines or experience the "on/off" phenomenon to L-dopa. Electroconvulsive therapy is an effective option for acute and maintenance treatment of Parkinson's disease in select patients. Inability to predict how long the beneficial effects of ECT therapy will last in patients with Parkinson's disease may be a reason why this treatment is underutilized by clinicians. More research is warranted to clarify parameters for application and duration of therapeutic benefit in individuals with difficult-to-treat Parkinson's disease.

Parkinson's Disease, Diabetes and Cognitive Impairment.

PubMed

Ashraghi, Mohammad R; Pagano, Gennaro; Polychronis, Sotirios; Niccolini, Flavia; Politis, Marios

2016-01-01

Parkinson's disease is a chronic neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. The pathophysiological mechanisms underlying Parkinson's are still unknown. Mitochondrial dysfunction, abnormal protein aggregation, increased neuroinflammation and impairment of brain glucose metabolism are shared processes among insulinresistance, diabetes and neurodegeneration and have been suggested as key mechanisms in development of Parkinson's and cognitive impairment. To review experimental and clinical evidence of underlying Parkinson's pathophysiology in common with diabetes and cognitive impairment. Anti-diabetic agents and recent patents for insulin-resistance that might be repositioned in the treatment of Parkinson's also have been included in this review. A narrative review using MEDLINE database. Common antidiabetic treatments such as DPP4 inhibitors, GLP-1 agonists and metformin have shown promise in the treatment of Parkinson's disease and cognitive impairment in animals and humans. Study of the pathophysiology of neurodegeneration common between diabetes and Parkinson's disease has given rise to new treatment possibilities. Patents published in the last 5 years could be used in novel approaches to Parkinson's treatment by targeting specific pathophysiology proteins, such as Nurr1, PINK1 and NrF2, while patents to improve penetration of the blood brain barrier could allow improved efficacy of existing treatments. Further studies using GLP-1 agonists and DPP-4 inhibitors to treat PD are warranted as they have shown promise.

Presymptomatic detection of Parkinson's disease.

PubMed

Jenner, P

1993-01-01

Presymptomatic detection of Parkinson's disease is necessary if neuroprotective therapies are to be utilized in its treatment. Various methods (PET, electrophysiology, enzyme assays, olfactory function) may be applicable but none has been rigorously evaluated. Other possible approaches are now considered. Plasma HVA levels (pHVA) in the presence of debrisoquine may reflect cerebral dopamine function. However, there are no detectable differences in pHVA between newly diagnosed and untreated parkinsonian patients and control subjects. Compensatory increases in dopamine turnover may mask a decrease in pHVA in the early stages of the disease. So, at present this technique could not be used as a diagnostic tool. Post-mortem studies of brain in Parkinson's disease may provide clues to biochemical markers indicative of nigral pathology. Mitochondrial complex I activity is reduced in substantia nigra in Parkinson's disease and it was reported also to be markedly reduced in blood platelets. However, subsequent studies suggest that the difference in platelet complex I activity is too small to be diagnostic of Parkinson's disease. There are also selective reductions in brain glutathione levels in Parkinson's disease restricted to substantia nigra, which do not occur in other neurodegenerative disorders and are not due to drug treatment. Importantly, in incidental Lewy body disease (preclinical Parkinson's disease) nigral glutathione levels are reduced to the same degree as in advanced Parkinson's disease. So, some peripheral index of altered glutathione function may be valuable in the early detection of the disease process.

[Sexual delinquency and Parkinson's disease].

PubMed

Berger, Ch; Mehrhoff, F W; Beier, K M; Meinck, H-M

2003-04-01

The risk of aberrant sexual behaviour such as hypersexuality, exhibitionism, or pederasty may be underestimated in Parkinson's disease and its therapy with high-dosage L-dopa or dopamine agonists. We describe two legal cases which are representative of the forensic assessment of these side effects. The first case brought to court was a 45-year-old man suffering for 20 years from Parkinson's disease who developed hypersexuality and exhibitionism under high-dose therapy with ropinirol. The second patient, a 57-year-old man with an 11-year history of Parkinson's disease, developed increased libido and pederasty under therapy with L-dopa and bromocriptine. We discuss the present literature concerning hypersexuality and sexually deviant behaviour in Parkinson's disease and dopaminergic therapy in the German legal context. Doctors treating Parkinson patients should be aware of increased sexual impulses or reduced behavioural control and ask specifically about them during anamnesis, and counteractive therapeutic strategies should be considered to prevent the occurrence of illegal sexually aberrant behavioural disorders.

Side effects induced by the acute levodopa challenge in Parkinson's Disease and atypical parkinsonisms.

PubMed

Vasta, Rosario; Nicoletti, Alessandra; Mostile, Giovanni; Dibilio, Valeria; Sciacca, Giorgia; Contrafatto, Donatella; Cicero, Calogero Edoardo; Raciti, Loredana; Luca, Antonina; Zappia, Mario

2017-01-01

Acute levodopa challenge may be performed to predict levodopa chronic responsiveness. The aim of the study was to investigate frequency of side effects during the acute levodopa challenge in PD and atypical parkinsonisms. We enrolled 34 de novo PD patients and 29 patients affected by atypical parkinsonisms (Multiple System Atrophy, MSA, n = 10; Progressive Supranuclear Palsy, PSP, n = 12 and Corticobasal Degeneration, CBD, n = 7) who underwent an acute levodopa challenge. Side effects occurring during test were recorded. Side effects were more frequent among atypical parkinsonisms as unique group when compared to PD patients (64.3% versus 23.5%; p-value 0.002) with an adjusted OR of 4.36 (95%CI 1.40-13.5). Each atypical parkinsonisms showed almost double occurrence of side effects (MSA 90%, PSP 41.7% and CBD 57%). Side effects during acute levodopa challenge may be frequent in atypical parkinsonisms. This information could be useful in order to better prepare the patient for the test. Furthermore, it could represent a useful cue in differential diagnosis with PD.

Parkinson disease.

PubMed

Poewe, Werner; Seppi, Klaus; Tanner, Caroline M; Halliday, Glenda M; Brundin, Patrik; Volkmann, Jens; Schrag, Anette-Eleonore; Lang, Anthony E

2017-03-23

Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability. The underlying molecular pathogenesis involves multiple pathways and mechanisms: α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport and neuroinflammation. Recent research into diagnostic biomarkers has taken advantage of neuroimaging in which several modalities, including PET, single-photon emission CT (SPECT) and novel MRI techniques, have been shown to aid early and differential diagnosis. Treatment of Parkinson disease is anchored on pharmacological substitution of striatal dopamine, in addition to non-dopaminergic approaches to address both motor and non-motor symptoms and deep brain stimulation for those developing intractable L-DOPA-related motor complications. Experimental therapies have tried to restore striatal dopamine by gene-based and cell-based approaches, and most recently, aggregation and cellular transport of α-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.

Large-Scale Wearable Sensor Deployment in Parkinson's Patients: The Parkinson@Home Study Protocol.

PubMed

Silva de Lima, Ana Lígia; Hahn, Tim; de Vries, Nienke M; Cohen, Eli; Bataille, Lauren; Little, Max A; Baldus, Heribert; Bloem, Bastiaan R; Faber, Marjan J

2016-08-26

Long-term management of Parkinson's disease does not reach its full potential because we lack knowledge about individual variations in clinical presentation and disease progression. Continuous and longitudinal assessments in real-life (ie, within the patients' own home environment) might fill this knowledge gap. The primary aim of the Parkinson@Home study is to evaluate the feasibility and compliance of using multiple wearable sensors to collect clinically relevant data. Our second aim is to address the usability of these data for answering clinical research questions. Finally, we aim to build a database for future validation of novel algorithms applied to sensor-derived data from Parkinson's patients during daily functioning. The Parkinson@Home study is a two-phase observational study involving 1000 Parkinson's patients and 250 physiotherapists. Disease status is assessed using a short version of the Parkinson's Progression Markers Initiative protocol, performed by certified physiotherapists. Additionally, participants will wear a set of sensors (smartwatch, smartphone, and fall detector), and use these together with a customized smartphone app (Fox Insight), 24/7 for 3 months. The sensors embedded within the smartwatch and fall detector may be used to estimate physical activity, tremor, sleep quality, and falls. Medication intake and fall incidents will be measured via patients' self-reports in the smartphone app. Phase one will address the feasibility of the study protocol. In phase two, mathematicians will distill relevant summary statistics from the raw sensor signals, which will be compared against the clinical outcomes. Recruitment of 300 participants for phase one was concluded in March, 2016, and the follow-up period will end in June, 2016. Phase two will include the remaining participants, and will commence in September, 2016. The Parkinson@Home study is expected to generate new insights into the feasibility of integrating self-collected information from

Dysphagia and sialorrhea: the relationship to Parkinson's disease.

PubMed

Nicaretta, Denise Hack; Rosso, Ana Lucia; Mattos, James Pitágoras de; Maliska, Carmelindo; Costa, Milton M B

2013-01-01

Dysphagia and sialorrhea in patients with Parkinson's disease are both automatically accepted as dependent on this neurological disease. The aim were to establish if these two complaints are a consequence or associated manifestations of Parkinson's disease. Two Parkinson's diseases groups from the same outpatients' population were studied. Patients in the first group, with dysphagia, were studied by videofluoroscopy. The second, with sialorrhea, were studied by the scintigraphic method, Videofluoroscopic examination of the oral, pharyngeal and esophageal phases of swallowing showed that 94% of Parkinson's diseases patients present, structural causes, not related to Parkinson's diseases, able to produce or intensify the observed disphagia. The scintigraphic examination of Parkinson's diseases patients with sialorrhea showed that there is no increase of serous saliva production. Nevertheless, showed a significantly higher velocity of saliva excretion in the Parkinson's diseases patients. Dysphagia can be due to the muscular rigidity often present in the Parkinson's diseases patient, or more usually by non Parkinson's disease associated causes. In Parkinson's diseases patients, sialorrhea is produced by saliva retention. Nevertheless, sialorrhea can produce discomfort in swallowing, although without a formal complaint of dysphagia. In this case, subclinical dysphagia must be considered. Sialorrhea is indicative of dysphagia or at least of subclinical dysphagia. As final conclusion, Parkinson's diseases can be an isolated cause of dysphagia and/or sialorrhea, but frequently, a factor unrelated to Parkinson's diseases is the main cause of or at least aggravates the dysphagia.

Cardiac abnormalities in Parkinson's disease and Parkinsonism.

PubMed

Scorza, Fulvio A; Fiorini, Ana C; Scorza, Carla A; Finsterer, Josef

2018-07-01

Though there is increasing evidence for primary cardiac disease in Parkinson's disease (PD) and Parkinsonism (PS), this evidence is hardly included in the general management of these patients. Literature review. PD is one of the most common age-related neurodegenerative disorders. Epidemiological studies have shown that PD is accompanied by high rates of premature death compared with the general population. In general, death in PD/PS is usually caused by determinant factors such as pneumonia, cerebrovascular, and cardiovascular disease. There is a significant body of literature demonstrating involvement of the heart in PD/PS. Cardiac involvement in PD/PS includes cardiac autonomic dysfunction, cardiomyopathy, coronary heart disease, arrhythmias, conduction defects, and sudden cardiac death (SCD), and sudden unexpected death in Parkinson's disease (SUDPAR). Cardiac abnormalities found in PD/PS are manifold but the most prominent is cardiac autonomic dysfunction. The frequency of coronary heart disease in PD is a matter of debate. Only rarely reported in PD/PS are cardiomyopathies, arrhythmias, and sudden cardiac death, and SUDPAR. It is particularly recommended that PD/PS patients are more intensively investigated cardiologically as soon as the diagnosis is established. Early recognition of cardiac involvement is important for preventing SCD and SUDPAR. Copyright © 2018 Elsevier Ltd. All rights reserved.

Michael J. Fox: Spurring Research on Parkinson's

MedlinePlus

... on. Feature: Parkinson's Disease Michael J. Fox: Spurring Research on Parkinson's Past Issues / Winter 2014 Table of ... founded the Michael J. Fox Foundation for Parkinson's Research in the year 2000. Photo courtesy of Shutterstock " ...

Treatment of early Parkinson's disease.

PubMed

Pahwa, Rajesh; Lyons, Kelly E

2014-08-01

This review summarizes currently available treatment options and treatment strategies, investigational treatments, and the importance of exercise for early Parkinson's disease. The available treatment options for early Parkinson's disease have changed little in the past decade and include carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B (MAO-B) inhibitors. However, we discuss changes in treatment strategies, including dosing and the use of combination therapy used in an attempt to reduce or delay the appearance of motor complications and other adverse events. We will also review several investigational treatments that have shown promise for the treatment of early Parkinson's disease, including a new extended release formulation of carbidopa/levodopa (IPX066), safinamide which inhibits MAO-B, dopamine uptake and glutamate and pardoprunox which is a 5HT-1A agonist and a partial dopamine agonist. Finally, we discuss recent studies focusing on exercise as an important component in the management of early Parkinson's disease. Advances in the management of early Parkinson's disease include evolving treatment strategies, new investigational treatments, and earlier implementation of various forms of exercise.

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

Excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in experimental approaches of Parkinsonism.

PubMed

Fernández-Espejo, Emilio; Bis-Humbert, Cristian

2018-06-06

3-iodo-l-tyrosine might play a role in Parkinson's disease since this molecule is able, at high concentration, to inhibit tyrosine-hydroxylase activity, the rate-limiting enzyme in dopamine biosynthesis. The possible Parkinson-like effects of 3-iodo-l-tyrosine were tested on three experimental approaches in mice: cultured substantia nigra neurons, the enteric nervous system of the jejunum after intra-peritoneal infusions, and the nigrostriatal system following unilateral intrabrain injections. 3-iodo-l-tyrosine, a physiological molecule, was used at concentrations higher than its serum levels in humans. Parkinson-like signs were evaluated through abnormal aggregation of α-synuclein and tyrosine-hydroxylase, loss of tyrosine-hydroxylase-expressing and striatum-projecting neurons and fibers, reduced tyrosine-hydroxylase density, and Parkinson-like motor and non-motor deficits. The retrograde tracer FluoroGold was used in the brain model. The findings revealed that excess amounts of 3-iodo-l-tyrosine induce Parkinson-like effects in the three experimental approaches. Thus, culture neurons of substantia nigra show, after 3-iodo-l-tyrosine exposure, intracytoplasmic inclusions that express α-synuclein and tyrosine-hydroxylase. Intra-peritoneal infusions of 3-iodo-l-tyrosine cause, in the long-term, α-synuclein aggregation, thicker α-synuclein-positive fibers, and loss of tyrosine-hydroxylase-positive cells and fibers in intramural plexuses and ganglia of the jejunum. Infusion of 3-iodo-l-tyrosine into the left dorsal striata of mice damages the nigrostriatal system, as revealed through lower striatal tyrosine-hydroxylase density, reduced number of tyrosine-hydroxylase-expressing and striatum-projecting neurons in the left substantia nigra, as well as the emergence of Parkinson-like behavioral deficits such as akinesia, bradykinesia, motor disbalance, and locomotion directional bias. In conclusion, excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in

Parkinson's Disease: The Newest Advances

MedlinePlus

Skip Navigation Bar Home Current Issue Past Issues Parkinson's Disease: The Newest Advances Past Issues / Summer 2006 Table ... number of genes that cause or contribute to Parkinson's disease (PD), as well as potential environmental risk factors. ...

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

Moving Parkinson care to the home.

PubMed

Dorsey, E Ray; Vlaanderen, Floris P; Engelen, Lucien Jlpg; Kieburtz, Karl; Zhu, William; Biglan, Kevin M; Faber, Marjan J; Bloem, Bastiaan R

2016-09-01

In many ways, the care of individuals with Parkinson disease does not meet their needs. Despite the documented benefits of receiving care from clinicians with Parkinson disease expertise, many patients (if not most) do not. Moreover, current care models frequently require older individuals with impaired mobility, cognition, and driving ability to be driven by overburdened caregivers to large, complex urban medical centers. Moving care to the patient's home would make Parkinson disease care more patient-centered. Demographic factors, including aging populations, and social factors, such as the splintering of the extended family, will increase the need for home-based care. Technological advances, especially the ability to assess and deliver care remotely, will enable the transition of care back to the home. However, despite its promise, this next generation of home-based care will have to overcome barriers, including outdated insurance models and a technological divide. Once these barriers are addressed, home-based care will increase access to high quality care for the growing number of individuals with Parkinson disease. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Sleep disorders and Parkinson disease; lessons from genetics.

PubMed

Gan-Or, Ziv; Alcalay, Roy N; Rouleau, Guy A; Postuma, Ronald B

2018-01-31

Parkinson disease is a common, age-related neurodegenerative disorder, projected to afflict millions of individuals in the near future. Understanding its etiology and identifying clinical, genetic or biological markers for Parkinson disease onset and progression is therefore of major importance. Various sleep-related disorders are the most common group of non-motor symptoms in advanced Parkinson disease, but they can also occur during its prodromal phase. However, with the exception of REM sleep behavior disorder, it is unclear whether they are part of the early pathological process of Parkinson disease, or if they develop as Parkinson disease advances because of treatments and neurodegeneration progression. The advancements in genetic studies in the past two decades have generated a wealth of information, and recent genetic studies offer new insight on the association of sleep-related disorders with Parkinson disease. More specifically, comparing genetic data between Parkinson disease and sleep-related disorders can clarify their association, which may assist in determining whether they can serve as clinical markers for Parkinson disease risk or progression. In this review, we discuss the current knowledge on the genetics of sleep-related disorders in Parkinson disease context, and the potential implications on research, diagnosis, counseling and treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Is the Parkinson Anxiety Scale comparable across raters?

PubMed

Forjaz, Maria João; Ayala, Alba; Martinez-Martin, Pablo; Dujardin, Kathy; Pontone, Gregory M; Starkstein, Sergio E; Weintraub, Daniel; Leentjens, Albert F G

2015-04-01

The Parkinson Anxiety Scale is a new scale developed to measure anxiety severity in Parkinson's disease specifically. It consists of three dimensions: persistent anxiety, episodic anxiety, and avoidance behavior. This study aimed to assess the measurement properties of the scale while controlling for the rater (self- vs. clinician-rated) effect. The Parkinson Anxiety Scale was administered to a cross-sectional multicenter international sample of 362 Parkinson's disease patients. Both patients and clinicians rated the patient's anxiety independently. A many-facet Rasch model design was applied to estimate and remove the rater effect. The following measurement properties were assessed: fit to the Rasch model, unidimensionality, reliability, differential item functioning, item local independency, interrater reliability (self or clinician), and scale targeting. In addition, test-retest stability, construct validity, precision, and diagnostic properties of the Parkinson Anxiety Scale were also analyzed. A good fit to the Rasch model was obtained for Parkinson Anxiety Scale dimensions A and B, after the removal of one item and rescoring of the response scale for certain items, whereas dimension C showed marginal fit. Self versus clinician rating differences were of small magnitude, with patients reporting higher anxiety levels than clinicians. The linear measure for Parkinson Anxiety Scale dimensions A and B showed good convergent construct with other anxiety measures and good diagnostic properties. Parkinson Anxiety Scale modified dimensions A and B provide valid and reliable measures of anxiety in Parkinson's disease that are comparable across raters. Further studies are needed with dimension C. © 2014 International Parkinson and Movement Disorder Society.

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

Pragmatic communication is impaired in Parkinson disease.

PubMed

Hall, Deborah; Ouyang, Bichun; Lonnquist, Eryn; Newcombe, Jill

2011-05-01

The purpose of this study was to determine whether severity of disease, cognitive function, age, gender, or amount of social interaction were associated with pragmatic dysfunction in Parkinson disease. No studies have previously been done to investigate variables that may be associated with pragmatic dysfunction in Parkinson disease. A case-control study was conducted with 17 Parkinson disease patients and 17 convenience controls. Each Parkinson disease patient and a control were interviewed, and their pragmatic skills were evaluated using a scale of pragmatic communication skills. Correlation analysis was used to determine what factors were associated with pragmatic dysfunction in the Parkinson disease patients. Cases scored lower on the pragmatic scale with a mean of 29.7 compared with 38.9 in the controls (p < .001) out of 40 possible points. The score on the scale of pragmatic communication skills had moderate to strong correlations with the MMSE (r = .81, p = .002), Unified Parkinson's Disease Rating Scale score (r = -.71, p = .002), and duration of disease (r = -.53, p = .03). These results show that Parkinson disease patients have impaired pragmatic function compared with controls on both verbal and nonverbal sections, and this impairment correlates with mental state, duration, and severity of disease.

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…

Parkinson's disease dementia: a neural networks perspective.

PubMed

Gratwicke, James; Jahanshahi, Marjan; Foltynie, Thomas

2015-06-01

In the long-term, with progression of the illness, Parkinson's disease dementia affects up to 90% of patients with Parkinson's disease. With increasing life expectancy in western countries, Parkinson's disease dementia is set to become even more prevalent in the future. However, current treatments only give modest symptomatic benefit at best. New treatments are slow in development because unlike the pathological processes underlying the motor deficits of Parkinson's disease, the neural mechanisms underlying the dementing process and its associated cognitive deficits are still poorly understood. Recent insights from neuroscience research have begun to unravel the heterogeneous involvement of several distinct neural networks underlying the cognitive deficits in Parkinson's disease dementia, and their modulation by both dopaminergic and non-dopaminergic transmitter systems in the brain. In this review we collate emerging evidence regarding these distinct brain networks to give a novel perspective on the pathological mechanisms underlying Parkinson's disease dementia, and discuss how this may offer new therapeutic opportunities. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Focused ultrasound subthalamotomy in patients with asymmetric Parkinson's disease: a pilot study.

PubMed

Martínez-Fernández, Raul; Rodríguez-Rojas, Rafael; Del Álamo, Marta; Hernández-Fernández, Frida; Pineda-Pardo, Jose A; Dileone, Michele; Alonso-Frech, Fernando; Foffani, Guglielmo; Obeso, Ignacio; Gasca-Salas, Carmen; de Luis-Pastor, Esther; Vela, Lydia; Obeso, José A

2018-01-01

Ablative neurosurgery has been used to treat Parkinson's disease for many decades. MRI-guided focused ultrasound allows focal lesions to be made in deep brain structures without skull incision. We investigated the safety and preliminary efficacy of unilateral subthalamotomy by focused ultrasound in Parkinson's disease. This prospective, open-label pilot study was done at CINAC (Centro Integral de Neurociencias), University Hospital HM Puerta del Sur in Madrid, Spain. Eligible participants had Parkinson's disease with markedly asymmetric parkinsonism. Patients with severe dyskinesia, history of stereotactic surgery or brain haemorrhage, a diagnosis of an unstable cardiac or psychiatric disease, or a skull density ratio of 0·3 or less were excluded. Enrolled patients underwent focused ultrasound unilateral subthalamotomy. The subthalamic nucleus was targeted by means of brain images acquired with a 3-Tesla MRI apparatus. Several sonications above the definitive ablation temperature of 55°C were delivered and adjusted according to clinical response. The primary outcomes were safety and a change in the motor status of the treated hemibody as assessed with part III of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) in both off-medication and on-medication states at 6 months. Adverse events were monitored up to 48 h after treatment and at scheduled clinic visits at 1, 3, and 6 months after treatment. The study is registered with ClinicalTrials.gov, number NCT02912871. Between April 26 and June 14, 2016, ten patients with markedly asymmetric parkinsonism that was poorly controlled pharmacologically were enrolled for focused ultrasound unilateral subthalamotomy. By 6 months follow-up, 38 incidents of adverse events had been recorded, none of which were serious or severe. Seven adverse events were present at 6 months. Three of these adverse events were directly related to subthalamotomy: off-medication dyskinesia in the treated arm

High rates of parkinsonism in adults with autism.

PubMed

Starkstein, Sergio; Gellar, Scott; Parlier, Morgan; Payne, Leslie; Piven, Joseph

2015-01-01

While it is now recognized that autism spectrum disorder (ASD) is typically a life-long condition, there exist only a handful of systematic studies on middle-aged and older adults with this condition. We first performed a structured examination of parkinsonian motor signs in a hypothesis-generating, pilot study (study I) of 19 adults with ASD over 49 years of age. Observing high rates of parkinsonism in those off atypical neuroleptics (2/12, 17 %) in comparison to published population rates for Parkinson's disease and parkinsonism, we examined a second sample of 37 adults with ASD, over 39 years of age, using a structured neurological assessment for parkinsonism. Twelve of the 37 subjects (32 %) met the diagnostic criteria for parkinsonism; however, of these, 29 subjects were on atypical neuroleptics, complicating interpretation of the findings. Two of eight (25 %) subjects not taking atypical neuroleptic medications met the criteria for parkinsonism. Combining subjects who were not currently taking atypical neuroleptic medications, across both studies, we conservatively classified 4/20 (20 %) with parkinsonism. We find a high frequency of parkinsonism among ASD individuals older than 39 years. If high rates of parkinsonism and potentially Parkinson's disease are confirmed in subsequent studies of ASD, this observation has important implications for understanding the neurobiology of autism and treatment of manifestations in older adults. Given the prevalence of autism in school-age children, the recognition of its life-long natural history, and the recognition of the aging of western societies, these findings also support the importance of further systematic study of other aspects of older adults with autism.

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

[The experimental models of Parkinson's disease in animals].

PubMed

Grigor'ian, G A; Bazian, A S

2007-01-01

The current review describes the modem Parkinson's disease models in animals, their advantages, limitations and disadvantages. It was noted that the most widespread up-to-date models based on etiology of the Parkinson's disease. Although toxins mostly produce the Parkinson's disease, a study of involved genes allows investigating not only inherited but also sporadic (not inherited) forms of disease since the same genes are involved in both cases. Mutations of genes lead to formation of "mutant" toxic proteins, which produce a death of the specialized neurons of the nigrostriatal dopaminergic system and the development of Parkinson's disease. A significant place in the review takes adescription of characteristics of the toxic models produced by 6-OHDA, MPTP and rotenone, their similarities and differences in pathogenetic mechanisms of the Parkinson's disease development. On the basis of the considered experimental models of Parkinson's disease a conclusion has been done that none of these models may in full and adequate scale imitate the entire clinical, pathophysiological, morphological, biochemical and other aspects of the Parkinson's disease development.

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.

Virtual house calls for Parkinson disease (Connect.Parkinson): study protocol for a randomized, controlled trial.

PubMed

Achey, Meredith A; Beck, Christopher A; Beran, Denise B; Boyd, Cynthia M; Schmidt, Peter N; Willis, Allison W; Riggare, Sara S; Simone, Richard B; Biglan, Kevin M; Dorsey, E Ray

2014-11-27

Interest in improving care for the growing number of individuals with chronic conditions is rising. However, access to care is limited by distance, disability, and distribution of doctors. Small-scale studies in Parkinson disease, a prototypical chronic condition, have suggested that delivering care using video house calls is feasible, offers similar clinical outcomes to in-person care, and reduces travel burden. We are conducting a randomized comparative effectiveness study (Connect.Parkinson) comparing usual care in the community to usual care augmented by virtual house calls with a Parkinson disease specialist. Recruitment is completed centrally using online advertisements and emails and by contacting physicians, support groups, and allied health professionals. Efforts target areas with a high proportion of individuals not receiving care from neurologists. Approximately 200 individuals with Parkinson disease and their care partners will be enrolled at 20 centers throughout the United States and followed for one year. Participants receive educational materials, then are randomized in a 1:1 ratio to continue their usual care (control arm) or usual care and specialty care delivered virtually (intervention arm). Care partners are surveyed about their time and travel burden and their perceived caregiver burden. Participants are evaluated via electronic survey forms and videoconferencing with a blinded independent rater at baseline and at 12 months. All study activities are completed remotely.The primary outcomes are: (1) feasibility, as measured by the proportion of visits completed, and (2) quality of life, as measured by the 39-item Parkinson's Disease Questionnaire. Secondary outcomes include measures of clinical benefit, quality of care, time and travel burden, and caregiver burden. Connect.Parkinson will evaluate the feasibility and effectiveness of using technology to deliver care into the homes of individuals with Parkinson disease. The trial may serve as a

Mild Cognitive Impairment in Parkinson's Disease-What Is It?

PubMed

Weil, Rimona S; Costantini, Alyssa A; Schrag, Anette E

2018-03-10

Mild cognitive impairment is a common feature of Parkinson's disease, even at the earliest disease stages, but there is variation in the nature and severity of cognitive involvement and in the risk of conversion to Parkinson's disease dementia. This review aims to summarise current understanding of mild cognitive impairment in Parkinson's disease. We consider the presentation, rate of conversion to dementia, underlying pathophysiology and potential biomarkers of mild cognitive impairment in Parkinson's disease. Finally, we discuss challenges and controversies of mild cognitive impairment in Parkinson's disease. Large-scale longitudinal studies have shown that cognitive involvement is important and common in Parkinson's disease and can present early in the disease course. Recent criteria for mild cognitive impairment in Parkinson's provide the basis for further study of cognitive decline and for the progression of different cognitive phenotypes and risk of conversion to dementia. Improved understanding of the underlying pathology and progression of cognitive change are likely to lead to opportunities for early intervention for this important aspect of Parkinson's disease.

Longitudinal Study of Gray Matter Changes in Parkinson Disease.

PubMed

Jia, X; Liang, P; Li, Y; Shi, L; Wang, D; Li, K

2015-12-01

The pathology of Parkinson disease leads to morphological brain volume changes. So far, the progressive gray matter volume change across time specific to patients with Parkinson disease compared controls remains unclear. Our aim was to investigate the pattern of gray matter changes in patients with Parkinson disease and to explore the progressive gray matter volume change specific to patients with Parkinson disease with disease progression by using voxel-based morphometry analysis. Longitudinal cognitive assessment and structural MR imaging of 89 patients with Parkinson disease (62 men) and 55 healthy controls (33 men) were from the Parkinson's Progression Markers Initiative data base, including the initial baseline and 12-month follow-up data. Two-way analysis of covariance was performed with covariates of age, sex, years of education, imaging data from multiple centers, and total intracranial volume by using Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra tool from SPM8 software. Gray matter volume changes for patients with Parkinson disease were detected with decreased gray matter volume in the frontotemporoparietal areas and the bilateral caudate, with increased gray matter volume in the bilateral limbic/paralimbic areas, medial globus pallidus/putamen, and the right occipital cortex compared with healthy controls. Progressive gray matter volume decrease in the bilateral caudate was found for both patients with Parkinson disease and healthy controls, and this caudate volume was positively associated with cognitive ability for both groups. The progressive gray matter volume increase specific to the patients with Parkinson disease was identified close to the left ventral lateral nucleus of thalamus, and a positive relationship was found between the thalamic volume and the tremor scores in a subgroup with tremor-dominant patients with Parkinson disease. The observed progressive changes in gray matter volume in Parkinson disease may provide

Managing Parkinson's

MedlinePlus

... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Parkinson's Foundation

MedlinePlus

... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Increased risk of parkinsonism associated with welding exposure.

PubMed

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

2012-10-01

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. 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. 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. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

A case of Parkinson's disease following dystonia.

PubMed

Yasuda, Chiharu; Takei, Takanobu; Uozumi, Takenori; Toyota, Tomoko; Yuhi, Tomoaki; Adachi, Hiroaki

2016-09-29

Parkinsonism and dystonia are both disorders of the extrapyramidal motor system, and some patients exhibit a complex of the two symptoms. Although several reports have referred to the coexistence of these disorders as parkinsonian disorders with dystonia, in the majority of cases, dystonia appeared after parkinsonism. DAT-scan is useful for the early diagnosis of Parkinson's disease (PD) and other types of parkinsonism such as dementia with Lewy bodies. This case report describes a 67-year old woman diagnosed with axial dystonia without parkinsonism 6 years previously, which had worsened despite treatment with Botulinum toxin injections, and hindered the patient's gait. The patient visited the hospital because of gait disturbances and DAT-scan showed a levodopa transducer decrease in the putamen. A few weeks later, she was re-admitted to hospital and exhibited Parkinsonism. Levodopa improved the gait disturbances but axial dystonia was unchanged, and a clinical diagnosis of PD was made. In the authors' opinion, this was a rare case of parkinsonian disorders with dystonia, characterized by the development of PD after dystonia. DAT-scan may be helpful for the diagnosis of patients with parkinsonian disorders with dystonia.

Dream Robber: Living with Parkinson's disease

MedlinePlus

... Current Issue Past Issues Dream Robber: Living with Parkinson's disease Past Issues / Summer 2006 Table of Contents For ... Now 65, he has been permanently grounded by Parkinson's disease, unable, due to the loss of motor control ...

Caribbean parkinsonism and other atypical parkinsonian disorders.

PubMed

Tolosa, Eduardo; Calandrella, Daniela; Gallardo, Marisol

2004-05-01

Atypical parkinsonism (AP) is a term applied to disorders characterized by parkinsonism that evolves rapidly, with poor or transient response to levodopa, or has other associated features such as early falls and postural instability, early autonomic failure, supranuclear gaze palsy, pyramidal or cerebellar signs, alien hand syndrome or severe ideomotor apraxia. The most common AP are multiple system atrophy, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Other APs include Caribbean parkinsonism (CP) and parkinsonism-dementia complex of Guam (PDC). In this review we provide an update in etiology, neuropathology, diagnosis and treatment of atypical parkinsonian disorders associated with protein tau deposit, also known as tauopathies.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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,more » 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.« less

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

Pharmacotherapy for Parkinson's disease.

PubMed

Chen, Jack J; Swope, David M

2007-12-01

The available pharmacotherapies for Parkinson's disease address symptomatology because no agent has been demonstrated to provide definite neuroprotection against the disease. Choice of pharmacotherapy must include consideration of short-term benefits as well as long-term consequences. Patients with mild Parkinson's disease often function adequately without symptomatic treatment. However, recent data suggest that initiation of treatment with a well-tolerated agent (e.g., the monoamine oxidase [MAO]-B inhibitor rasagiline) in the absence of functional impairment is associated with improved long-term outcomes. Consideration should also be given to many patient-specific factors, including patient expectations, level of disability, employment status, functional as well as chronologic age, expected efficacy and tolerability of drugs, and response to previous Parkinson's disease therapies. Increasingly, initial monotherapy begins with a nondopaminergic agent or, if the patient is considered functionally young, a dopamine agonist. Since Parkinson's disease is a progressive disorder, adjustments to pharmacotherapy must be expected over time. When greater symptomatic relief is desired, or in the more frail elderly patient, levodopa therapy should be considered. If motor fluctuations develop, addition of a catechol-O-methyltransferase inhibitor or MAO-B inhibitor should be considered. For management of levodopa-induced dyskinesias, addition of amantadine is an option. Surgery may be considered when patients need additional symptomatic control or are experiencing severe motor complications despite pharmacologically optimized therapy.

Placebo influences on dyskinesia in Parkinson's disease.

PubMed

Goetz, Christopher G; Laska, Eugene; Hicking, Christine; Damier, Philippe; Müller, Thomas; Nutt, John; Warren Olanow, C; Rascol, Olivier; Russ, Hermann

2008-04-15

Clinical features that are prognostic indicators of placebo response among dyskinetic Parkinson's disease patients were determined. Placebo-associated improvements occur in Parkinsonism, but responses in dyskinesia have not been studied. Placebo data from two multicenter studies with identical design comparing sarizotan to placebo for treating dyskinesia were accessed. Sarizotan (2 mg/day) failed to improve dyskinesia compared with placebo, but both treatments improved dyskinesia compared with baseline. Stepwise regression identified baseline characteristics that influenced dyskinesia response to placebo, and these factors were entered into a logistic regression model to quantify their influence on placebo-related dyskinesia improvements and worsening. Because placebo-associated improvements in Parkinsonism have been attributed to heightened dopaminergic activity, we also examined the association between changes in Parkinsonism and dyskinesia. Four hundred eighty-four subjects received placebo treatment; 178 met criteria for placebo-associated dyskinesia improvement and 37 for dyskinesia worsening. Older age, lower baseline Parkinsonism score, and lower total daily levodopa doses were associated with placebo-associated improvement, whereas lower baseline dyskinesia score was associated with placebo-associated worsening. Placebo-associated dyskinesia changes were not correlated with Parkinsonism changes, and all effects in the sarizotan group were statistically explained by the placebo-effect regression model. Dyskinesias are affected by placebo treatment. The absence of correlation between placebo-induced changes in dyskinesia and Parkinsonism argues against a dopaminergic activation mechanism to explain placebo-associated improvements in dyskinesia. The magnitude and variance of placebo-related changes and the factors that influence them can be helpful in the design of future clinical trials of antidyskinetic agents. 2007 Movement Disorder Society

Placebo Influences on Dyskinesia in Parkinson's Disease

PubMed Central

Goetz, Christopher G.; Laska, Eugene; Hicking, Christine; Damier, Philippe; Müller, Thomas; Nutt, John; Olanow, C. Warren; Rascol, Olivier; Russ, Hermann

2009-01-01

Clinical features that are prognostic indicators of placebo response among dyskinetic Parkinson's disease patients were determined. Placebo-associated improvements occur in Parkinsonism, but responses in dyskinesia have not been studied. Placebo data from two multicenter studies with identical design comparing sarizotan to placebo for treating dyskinesia were accessed. Sarizotan (2 mg/day) failed to improve dyskinesia compared with placebo, but both treatments improved dyskinesia compared with baseline. Stepwise regression identified baseline characteristics that influenced dyskinesia response to placebo, and these factors were entered into a logistic regression model to quantify their influence on placebo-related dyskinesia improvements and worsening. Because placebo-associated improvements in Parkinsonism have been attributed to heightened dopaminergic activity, we also examined the association between changes in Parkinsonism and dyskinesia. Four hundred eighty-four subjects received placebo treatment; 178 met criteria for placebo-associated dyskinesia improvement and 37 for dyskinesia worsening. Older age, lower baseline Parkinsonism score, and lower total daily levodopa doses were associated with placebo-associated improvement, whereas lower baseline dyskinesia score was associated with placebo-associated worsening. Placebo-associated dyskinesia changes were not correlated with Parkinsonism changes, and all effects in the sarizotan group were statistically explained by the placebo-effect regression model. Dyskinesias are affected by placebo treatment. The absence of correlation between placebo-induced changes in dyskinesia and Parkinsonism argues against a dopaminergic activation mechanism to explain placebo-associated improvements in dyskinesia. The magnitude and variance of placebo-related changes and the factors that influence them can be helpful in the design of future clinical trials of antidyskinetic agents. PMID:18175337

The frequency of buccopalpebral reflex in Parkinson disease.

PubMed

Eser, Hülya; Ünal, Yasemin; Kutlu, Gülnihal; Öcal, Ruhsen; İnan, Levent Ertuğrul

2016-11-17

This study aimed to define the frequency of a primitive reflex, the buccopalpebral reflex (BPR), and its association with the clinical situation in patients with Parkinson disease. Between May 2010 and May 2011, 222 patients, 115 with Parkinson disease and 107 patients without any sign of neurodegenerative disease, were included in the study. All included patients were examined for BPR and snout reflex and were also evaluated with the Mini Mental State Examination. All patients with Parkinson disease were classified with the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr Score to determine their clinical severity. Sixteen patients with Parkinson disease (13.9%) had a BPR (+) and 4 patients in the control group (3.7%) (P < 0.001). The UPDRS score, UPDRS daily life activities score, and UPDRS motor system score were all higher in the group with BPR (+). All patients with a BPR also had a positive snout reflex. BPR is more frequent in patients with Parkinson disease than in patients without a neurodegenerative disease.

Protein Kinases and Parkinson's Disease.

PubMed

Mehdi, Syed Jafar; Rosas-Hernandez, Hector; Cuevas, Elvis; Lantz, Susan M; Barger, Steven W; Sarkar, Sumit; Paule, Merle G; Ali, Syed F; Imam, Syed Z

2016-09-20

Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson's disease has intensified the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved and are used clinically for other indications. Kinase inhibitors represent a family of popular molecules for the treatment and prevention of various cancers, and have emerged as strong candidates for such repurposing because numerous serine/threonine and tyrosine kinases have been implicated in the pathobiology of Parkinson's disease. This review focuses on various kinase-dependent pathways associated with the expression of Parkinson's disease pathology, and evaluates how inhibitors of these pathways might play a major role as effective therapeutic molecules.

Neuromuscular rate of force development deficit in Parkinson disease.

PubMed

Hammond, Kelley G; Pfeiffer, Ronald F; LeDoux, Mark S; Schilling, Brian K

2017-06-01

Bradykinesia and reduced neuromuscular force exist in Parkinson disease. The interpolated twitch technique has been used to evaluate central versus peripheral manifestations of neuromuscular strength in healthy, aging, and athletic populations, as well as moderate to advanced Parkinson disease, but this method has not been used in mild Parkinson disease. This study aimed to evaluate quadriceps femoris rate of force development and quantify potential central and peripheral activation deficits in individuals with Parkinson disease. Nine persons with mild Parkinson Disease (Hoehn & Yahr≤2, Unified Parkinson Disease Rating Scale total score=mean 19.1 (SD 5.0)) and eight age-matched controls were recruited in a cross-sectional investigation. Quadriceps femoris voluntary and stimulated maximal force and rate of force development were evaluated using the interpolated twitch technique. Thirteen participants satisfactorily completed the protocol. Individuals with early Parkinson disease (n=7) had significantly slower voluntary rate of force development (p=0.008; d=1.97) and rate of force development ratio (p=0.004; d=2.18) than controls (n=6). No significant differences were found between groups for all other variables. Persons with mild-to-moderate Parkinson disease display disparities in rate of force development, even without deficits in maximal force. The inability to produce force at a rate comparable to controls is likely a downstream effect of central dysfunction of the motor pathway in Parkinson disease. Copyright © 2017. Published by Elsevier Ltd.

Vocal tract characteristics in Parkinson's disease.

PubMed

Gillivan-Murphy, Patricia; Carding, Paul; Miller, Nick

2016-06-01

Voice tremor is strongly linked to the Parkinson's disease speech-voice symptom complex. Little is known about the underlying anatomic source(s) of voice tremor when it occurs. We review recent literature addressing this issue. Additionally we report findings from a study we conducted employing rating of vocal tract structures viewed using nasolaryngoscopy during vocal and nonspeech tasks. In Parkinson's disease, using laryngeal electromyography, tremor has not been identified in muscles in the vocal folds even when perceived auditorily. Preliminary findings using nasolaryngoscopy suggest that Parkinson's disease voice tremor is not associated with the vocal folds and may involve the palate, the global larynx, and the arytenoids. Tremor in the vertical larynx on /a/, and tremor in the arytenoid cartilages on /s/ differentiated patients with Parkinson's disease from neurologically healthy controls. Visual reliable detection of tremor when it is absent or borderline present, is challenging. Parkinson's disease voice tremor is likely to be related to oscillatory movement in structures across the vocal tract rather than just the vocal folds. To progress clinical practice, more refined tools for the visual rating of tremor would be beneficial. How far voice tremor represents a functionally significant factor for speakers would also add to the literature.

Parkinson's disease - the story of an eponym.

PubMed

Goedert, Michel; Compston, Alastair

2018-01-01

One of the most prevalent neurodegenerative diseases worldwide is still referred to as 'Parkinson's disease'. The condition is named after James Parkinson who, in 1817, described the shaking palsy (paralysis agitans). In the bicentennial year of this publication, we trace when and why the shaking palsy became Parkinson's disease. The term was coined by William Rutherford Sanders of Edinburgh in 1865 and later entered general usage through the influence of Jean-Martin Charcot and the school that he nurtured at the Salpêtrière Hospital in Paris. Despite a move towards more mechanism-based nosology for many medical conditions in recent years, the Parkinson's disease eponym remains in place, celebrating the life and work of this doctor, palaeontologist and political activist.

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 ...

Diagnostic Value of the Impairment of Olfaction in Parkinson's Disease

PubMed Central

Casjens, Swaantje; Eckert, Angelika; Woitalla, Dirk; Ellrichmann, Gisa; Turewicz, Michael; Stephan, Christian; Eisenacher, Martin; May, Caroline; Meyer, Helmut E.; Brüning, Thomas; Pesch, Beate

2013-01-01

Background Olfactory impairment is increasingly recognized as an early symptom in the development of Parkinson's disease. Testing olfactory function is a non-invasive method but can be time-consuming which restricts its application in clinical settings and epidemiological studies. Here, we investigate odor identification as a supportive diagnostic tool for Parkinson's disease and estimate the performance of odor subsets to allow a more rapid testing of olfactory impairment. Methodology/Principal Findings Odor identification was assessed with 16 Sniffin' sticks in 148 Parkinson patients and 148 healthy controls. Risks of olfactory impairment were estimated with proportional odds models. Random forests were applied to classify Parkinson and non-Parkinson patients. Parkinson patients were rarely normosmic (identification of more than 12 odors; 16.8%) and identified on average seven odors whereas the reference group identified 12 odors and showed a higher prevalence of normosmy (31.1%). Parkinson patients with rigidity dominance had a twofold greater prevalence of olfactory impairment. Disease severity was associated with impairment of odor identification (per score point of the Hoehn and Yahr rating OR 1.87, 95% CI 1.26–2.77). Age-related impairment of olfaction showed a steeper gradient in Parkinson patients. Coffee, peppermint, and anise showed the largest difference in odor identification between Parkinson patients and controls. Random forests estimated a misclassification rate of 22.4% when comparing Parkinson patients with healthy controls using all 16 odors. A similar rate (23.8%) was observed when only the three aforementioned odors were applied. Conclusions/Significance Our findings indicate that testing odor identification can be a supportive diagnostic tool for Parkinson's disease. The application of only three odors performed well in discriminating Parkinson patients from controls, which can facilitate a wider application of this method as a point

Serum lipid alterations in GBA-associated Parkinson's disease.

PubMed

Guedes, Leonor Correia; Chan, Robin Barry; Gomes, Marcos António; Conceição, Vasco A; Machado, Raquel Bouça; Soares, Tiago; Xu, Yimeng; Gaspar, Paulo; Carriço, Joao André; Alcalay, Roy N; Ferreira, Joaquim J; Outeiro, Tiago Fleming; Miltenberger-Miltenyi, Gabriel

2017-11-01

Mutations in the GBA gene, encoding for the lysosomal enzyme glucocerebrosidase, are associated with Gaucher disease. Alterations in plasma sphingolipids have been reported in Gaucher, and similarly in brain extracts in Lewy body disease. As GBA mutations are prevalent risk factors for Parkinson's disease and overlap of molecular pathways are presumable, here we assessed the lipid profiles in Parkinson's patients with and without GBA mutations. We sequenced all GBA exons in 415 Parkinson's patients, previously genotyped for LRRK2. 64 patients (29 GBA positive vs. 35 non-GBA-carriers including 18 LRRK2 positive and 17 non-mutated) were analyzed for chitotriosidase activity and for the concentration of 40 lipid classes using HPLC-MS. 29/415 patients (6.9%) carried 8 different GBA mutations associated with Gaucher or Parkinson's, including one novel mutation. Chitotriosidase activity was similar across the genetic groups, while the levels of key lipids were altered in GBA mutation carriers: Monohexosylceramide, Ceramide and Sphingomyelin were elevated; while Phosphatidic acid (PA), Phosphatidylethanolamine (PE), Plasmalogen phosphatidylethanolamine (PEp) and Acyl Phosphatidylglycerol (AcylPG) were decreased. The results suggest an important role for these lipids in GBA mediated Parkinson's disease and assist in the identification of common pathways between Gaucher and Parkinson's. Ultimately, our findings may lead to the identification of novel biomarkers for individuals at increased risk of developing Parkinson's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

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. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Thiazolidinediones and Parkinson Disease: A Cohort Study.

PubMed

Connolly, John G; Bykov, Katsiaryna; Gagne, Joshua J

2015-12-01

Thiazolidinediones, a class of medications indicated for the treatment of type 2 diabetes mellitus, reduce inflammation and have been shown to provide a therapeutic benefit in animal models of Parkinson disease. We examined the association between treatment with thiazolidinediones and the onset of Parkinson disease in older individuals. We performed a cohort study of 29,397 Medicare patients enrolled in state pharmaceutical benefits programs who initiated treatment with thiazolidinediones or sulfonylureas during the years 1997 through 2005 and had no prior diagnosis of Parkinson disease. New users of thiazolidinediones were propensity score matched to new users of sulfonylureas and followed to determine whether they were diagnosed with Parkinson disease. We used Cox proportional hazards models to compare time to diagnosis of Parkinson disease in the propensity score-matched populations. To assess the association with duration of use, we performed several analyses that required longer continuous use of medications. In the primary analysis, thiazolidinedione users had a hazard ratio for a diagnosis of Parkinson disease of 1.09 (95% confidence interval: 0.71, 1.66) when compared with sulfonylurea users. Increasing the duration-of-use requirements to 10 months did not substantially change the association; the hazard ratios ranged from 1.00 (95% confidence interval: 0.49, 2.05) to 1.17 (95% confidence interval: 0.60, 2.25). Thiazolidinedione use was not associated with a longer time to diagnosis of Parkinson disease than was sulfonylurea use, regardless of duration of exposure. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Occupation and risk of parkinsonism: a multicenter case-control study.

PubMed

Tanner, Caroline M; Ross, G Webster; Jewell, Sarah A; Hauser, Robert A; Jankovic, Joseph; Factor, Stewart A; Bressman, Susan; Deligtisch, Amanda; Marras, Connie; Lyons, Kelly E; Bhudhikanok, Grace S; Roucoux, Diana F; Meng, Cheryl; Abbott, Robert D; Langston, J William

2009-09-01

We examined risk of parkinsonism in occupations (agriculture, education, health care, welding, and mining) and toxicant exposures (solvents and pesticides) putatively associated with parkinsonism. To investigate occupations, specific job tasks, or exposures and risk of parkinsonism and clinical subtypes. Case-control. Eight movement disorders centers in North America. Inclusion criteria were parkinsonism (>or=2 cardinal signs), diagnosis within 8 years of recruitment (to minimize survival bias), and ability to participate in detailed telephone interviews. Control subjects were primarily nonblood relatives or acquaintances of patients. This multicenter case-control study compared lifelong occupational and job task histories to determine associations with parkinsonism and certain clinical subtypes (postural instability and gait difficulty and age at diagnosis parkinsonism. Unexpected increased risks associated with legal, construction and extraction, or religious occupations were not maintained after adjustment for duration. Risk of parkinsonism increased with pesticide use (odds ratio, 1.90; 95% confidence interval, 1.12-3.21), use of any of 8 pesticides mechanistically associated with experimental parkinsonism (2.20; 1.02-4.75), and use of 2,4-dichlorophenoxyacetic acid (2.59; 1.03-6.48). None of the specific occupations, job tasks, or task-related exposures were associated with younger age at diagnosis (parkinsonism. Tobacco use was inversely associated with parkinsonism risk. The association of disease risk with pesticides support a toxicant-induced cause of parkinsonism.

Increased pulsatility index supports diagnosis of vascular parkinsonism versus idiopathic Parkinson's disease.

PubMed

Caba, L M; Ferrairó, J I T; Torres, I M; Costa, J F V; Muñoz, R B; Martin, A L

2017-12-29

The diagnosis of vascular parkinsonism (VP) is based on a series of clinical criteria and neuroimaging findings. An increase in transcranial Doppler ultrasonography pulsatility index (PI) has been described as a frequent finding in patients with VP. We aimed to confirm this association and to determine the PI value with the highest sensitivity and specificity for diagnosis of VP. PI was determined in all patients admitted to Hospital Universitari i Politècnic La Fe due to parkinsonism between January 2012 and June 2016. We assessed the probability of having VP based on PI values in patients with a definite diagnosis of either VP or idiopathic Parkinson's disease (IPD). A ROC curve was created to determine the PI value with the highest sensitivity and specificity. We assessed a total of 146 patients with suspected parkinsonism; 54 (37%) were diagnosed with IPD and 15 (10%) with VP. Patients with VP were significantly older than those with IPD (mean age of 79 vs 68.5, P=.00144) and had a higher PI (median of 1.29 [IQR: 1.09-1.38] vs 0.96 [IQR: 0.89-1.16], P=.01328). In our sample, a PI of 1.09 conferred 84% sensitivity and 70% specificity. In our series, the PI was significantly higher in patients with VP than in those with IPD. We therefore support the use of transcranial Doppler ultrasonography for the initial assessment of elderly patients with akinetic-rigid syndrome. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Parkinson's Disease Subtypes in the Oxford Parkinson Disease Centre (OPDC) Discovery Cohort.

PubMed

Lawton, Michael; Baig, Fahd; Rolinski, Michal; Ruffman, Claudio; Nithi, Kannan; May, Margaret T; Ben-Shlomo, Yoav; Hu, Michele T M

2015-01-01

Within Parkinson's there is a spectrum of clinical features at presentation which may represent sub-types of the disease. However there is no widely accepted consensus of how best to group patients. Use a data-driven approach to unravel any heterogeneity in the Parkinson's phenotype in a well-characterised, population-based incidence cohort. 769 consecutive patients, with mean disease duration of 1.3 years, were assessed using a broad range of motor, cognitive and non-motor metrics. Multiple imputation was carried out using the chained equations approach to deal with missing data. We used an exploratory and then a confirmatory factor analysis to determine suitable domains to include within our cluster analysis. K-means cluster analysis of the factor scores and all the variables not loading into a factor was used to determine phenotypic subgroups. Our factor analysis found three important factors that were characterised by: psychological well-being features; non-tremor motor features, such as posture and rigidity; and cognitive features. Our subsequent five cluster model identified groups characterised by (1) mild motor and non-motor disease (25.4%), (2) poor posture and cognition (23.3%), (3) severe tremor (20.8%), (4) poor psychological well-being, RBD and sleep (18.9%), and (5) severe motor and non-motor disease with poor psychological well-being (11.7%). Our approach identified several Parkinson's phenotypic sub-groups driven by largely dopaminergic-resistant features (RBD, impaired cognition and posture, poor psychological well-being) that, in addition to dopaminergic-responsive motor features may be important for studying the aetiology, progression, and medication response of early Parkinson's.

[Sleep disturbances in Parkinson's disease: characteristics, evaluation and therapeutic approaches].

PubMed

Faludi, Béla; Janszky, József; Komoly, Sámuel; Kovács, Norbert

2015-07-05

Parkinson's disease is a well known representent of the movement disorder group of neurological disorders. The diagnosis of Parkinson's disease is based on specific symptoms and signs of movement abnormalities. In addition to classic motor symptoms, Parkinson's disease has characteristic non-motor features, and some of these emerges the classic signs. The authors discuss characteristics and therapeutic interventions in Parkinson's disease related sleep disturbances. The authors reviewed and summarised literature data on sleep disorders in Parkinson's disease published in the PubMed database up to January 2015. Sleep problems are important non-motor complains (insomnia, hypersomnia, REM behaviour disorder, sleep apnea and restless legs syndrome). The neurodegenerative process of the brain-stem, the effect of symptoms of Parkinson's disease on sleep and concomitant sleep disorders constitute the background of the patient's complains. Appropriate diagnosis and therapy of the consequential or concomitant sleep disorders in Parkinson's disease will help to improve the patient's quality of life.

Parkinson's Disease

MedlinePlus

... in sexual desire or performance. Prevention Because the cause of Parkinson's is unknown, proven ways to prevent the disease also remain a mystery. However, some research has shown that caffeine — which is found in coffee, tea and cola — ...

Management of Parkinson׳s disease: Current and future pharmacotherapy.

PubMed

Kakkar, Ashish Kumar; Dahiya, Neha

2015-03-05

Parkinson׳s disease (PD) is chronic progressive neurodegenerative disorder characterized by profound loss of dopaminergic neurons in the nigrostriatal pathway. It is recognized by the cardinal clinical features of bradykinesia, rigidity, tremor and postural instability. Current therapeutic options are primarily dopamine replacement strategies that only provide symptomatic improvement without affecting progressive neuronal loss. These treatments often fail to provide sustained clinical benefit and most patients develop motor fluctuations and dyskinesias as the disease progresses. Additionally, non-motor symptoms such as autonomic disturbances, sensory alterations, olfactory dysfunction, mood disorders, sleep disturbances and cognitive impairment cause considerable functional disability in these patients and these features often fail to respond to standard dopaminergic treatments. This mini review outlines the current pharmacotherapeutic options for PD and highlights the emerging experimental therapies in various phases of clinical development. Copyright © 2015 Elsevier B.V. All rights reserved.

Ability to Consent to Parkinson Disease Research

MedlinePlus

... Steven Karceski, MD The ability to consent to Parkinson disease research Eran Klein, MD, PhD WHAT IS THIS ... 1 on giving consent to be part of Parkinson disease (PD) research. People with PD often want to ...

Nicotinic receptors as CNS targets for Parkinson's disease.

PubMed

Quik, Maryka; Bordia, Tanuja; O'Leary, Kathryn

2007-10-15

Parkinson's disease is a debilitating neurodegenerative movement disorder characterized by damage to the nigrostriatal dopaminergic system. Current therapies are symptomatic only and may be accompanied by serious side effects. There is therefore a continual search for novel compounds for the treatment of Parkinson's disease symptoms, as well as to reduce or halt disease progression. Nicotine administration has been reported to improve motor deficits that arise with nigrostriatal damage in parkinsonian animals and in Parkinson's disease. In addition, nicotine protects against nigrostriatal damage in experimental models, findings that have led to the suggestion that the reduced incidence of Parkinson's disease in smokers may be due to the nicotine in tobacco. Altogether, these observations suggest that nicotine treatment may be beneficial in Parkinson's disease. Nicotine interacts with multiple nicotinic receptor (nAChR) subtypes in the peripheral and central nervous system, as well as in skeletal muscle. Work to identify the subtypes affected in Parkinson's disease is therefore critical for the development of targeted therapies. Results show that striatal alpha6beta2-containing nAChRs are particularly susceptible to nigrostriatal damage, with a decline in receptor levels that closely parallels losses in striatal dopamine. In contrast, alpha4beta2-containing nAChRs are decreased to a much smaller extent under the same conditions. These observations suggest that development of nAChR agonists or antagonists targeted to alpha6beta2-containing nAChRs may represent a particularly relevant target for Parkinson's disease therapeutics.

[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.

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

[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.

Speech and swallowing disorders in Parkinson disease.

PubMed

Sapir, Shimon; Ramig, Lorraine; Fox, Cynthia

2008-06-01

To review recent research and clinical studies pertaining to the nature, diagnosis, and treatment of speech and swallowing disorders in Parkinson disease. Although some studies indicate improvement in voice and speech with dopamine therapy and deep brain stimulation of the subthalamic nucleus, others show minimal or adverse effects. Repetitive transcranial magnetic stimulation of the mouth motor cortex and injection of collagen in the vocal folds have preliminary data supporting improvement in phonation in people with Parkinson disease. Treatments focusing on vocal loudness, specifically LSVT LOUD (Lee Silverman Voice Treatment), have been effective for the treatment of speech disorders in Parkinson disease. Changes in brain activity due to LSVT LOUD provide preliminary evidence for neural plasticity. Computer-based technology makes the Lee Silverman Voice Treatment available to a large number of users. A rat model for studying neuropharmacologic effects on vocalization in Parkinson disease has been developed. New diagnostic methods of speech and swallowing are also available as the result of recent studies. Speech rehabilitation with the LSVT LOUD is highly efficacious and scientifically tested. There is a need for more studies to improve understanding, diagnosis, prevention, and treatment of speech and swallowing disorders in Parkinson disease.

Parkinson's: a syndrome rather than a disease?

PubMed

Titova, Nataliya; Padmakumar, C; Lewis, Simon J G; Chaudhuri, K Ray

2017-08-01

Emerging concepts suggest that a multitude of pathology ranging from misfolding of alpha-synuclein to neuroinflammation, mitochondrial dysfunction, and neurotransmitter driven alteration of brain neuronal networks lead to a syndrome that is commonly known as Parkinson's disease. The complex underlying pathology which may involve degeneration of non-dopaminergic pathways leads to the expression of a range of non-motor symptoms from the prodromal stage of Parkinson's to the palliative stage. Non-motor clinical subtypes, cognitive and non-cognitive, have now been proposed paving the way for possible subtype specific and non-motor treatments, a key unmet need currently. Natural history of these subtypes remains unclear and need to be defined. In addition to in vivo biomarkers which suggest variable involvement of the cholinergic and noradrenergic patterns of the Parkinson syndrome, abnormal alpha-synuclein accumulation have now been demonstrated in the gut, pancreas, heart, salivary glands, and skin suggesting that Parkinson's is a multi-organ disorder. The Parkinson's phenotype is thus not just a dopaminergic motor syndrome, but a dysfunctional multi-neurotransmitter pathway driven central and peripheral nervous system disorder that possibly ought to be considered a syndrome and not a disease.

Four Cases of Parkinson Disease Diagnosed During the Postpartum Period.

PubMed

Maltête, David; Grangeon, Lou; Le Goff, Floriane; Ozel, Gulden; Fetter, Damien; Ahtoy, Patrick; Temgoua, Olivier; Rouillé, Audrey; Lefaucheur, Romain

2017-07-01

There is little experience with the effect of pregnancy on Parkinson disease because the number of women with Parkinson disease who are of childbearing age is small. We report four cases beginning during the postpartum period and discuss the potential contribution of different factors that may influence the occurrence of Parkinson disease in this time period. Four women aged 29-35 years developed arm tremor, shoulder pain, dizziness, or decreased dexterity of the hand in the first few days or months after childbirth. They were initially diagnosed with postpartum depression or psychogenic parkinsonism. Finally, dopamine transporter imaging confirmed the diagnosis of young-onset Parkinson disease. Early-onset Parkinson disease may present in postpartum women. In women with atypical motor symptoms in addition to depression, this diagnosis should be considered.

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

MedlinePlus

... turn JavaScript on. Feature: Parkinson's Disease Parkinson's Disease Research at NIH Past Issues / Winter 2014 Table of ... Disorders/All-Disorders/Parkinsons-Disease-Information-Page What Research Is Being Done? The National Institute of Neurological ...

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.

NIH Research: Advances in Parkinson's Disease Research

MedlinePlus

... of this page please turn JavaScript on. NIH Research: Advances in Parkinson's Disease Research Past Issues / Winter 2014 Table of Contents Story ... Photo courtesy of NIH Advances in Parkinson's Disease Research Story Landis, Ph.D., has been Director of ...

Substantia Nigra Free Water Increases Longitudinally in Parkinson Disease.

PubMed

Guttuso, T; Bergsland, N; Hagemeier, J; Lichter, D G; Pasternak, O; Zivadinov, R

2018-02-01

Free water in the posterior substantia nigra obtained from a bi-tensor diffusion MR imaging model has been shown to significantly increase over 1- and 4-year periods in patients with early-stage idiopathic Parkinson disease compared with healthy controls, which suggests that posterior substantia nigra free water may be an idiopathic Parkinson disease progression biomarker. Due to the known temporal posterior-to-anterior substantia nigra degeneration in idiopathic Parkinson disease, we assessed longitudinal changes in free water in both the posterior and anterior substantia nigra in patients with later-stage idiopathic Parkinson disease and age-matched healthy controls for comparison. Nineteen subjects with idiopathic Parkinson disease and 19 age-matched healthy control subjects were assessed on the same 3T MR imaging scanner at baseline and after approximately 3 years. Baseline mean idiopathic Parkinson disease duration was 7.1 years. Both anterior and posterior substantia nigra free water showed significant intergroup differences at baseline ( P < .001 and P = .014, respectively, idiopathic Parkinson disease versus healthy controls); however, only anterior substantia nigra free water showed significant longitudinal group × time interaction increases ( P = .021, idiopathic Parkinson disease versus healthy controls). There were no significant longitudinal group × time interaction differences found for conventional diffusion tensor imaging or free water-corrected DTI assessments in either the anterior or posterior substantia nigra. Results from this study provide further evidence supporting substantia nigra free water as a promising disease-progression biomarker in idiopathic Parkinson disease that may help to identify disease-modifying therapies if used in future clinical trials. Our novel finding of longitudinal increases in anterior but not posterior substantia nigra free water is potentially a result of the much longer disease duration of our cohort compared

Unilateral pedunculopontine stimulation improves falls in Parkinson's disease.

PubMed

Moro, Elena; Hamani, Clement; Poon, Yu-Yan; Al-Khairallah, Thamar; Dostrovsky, Jonathan O; Hutchison, William D; Lozano, Andres M

2010-01-01

Postural instability and falls are a major source of disability in patients with advanced Parkinson's disease. These problems are currently not well addressed by either pharmacotherapy nor by subthalamic nucleus deep-brain stimulation surgery. The neuroanatomical substrates of posture and gait are poorly understood but a number of important observations suggest a major role for the pedunculopontine nucleus and adjacent areas in the brainstem. We conducted a double-blinded evaluation of unilateral pedunculopontine nucleus deep-brain stimulation in a pilot study in six advanced Parkinson's disease patients with significant gait and postural abnormalities. There was no significant difference in the double-blinded on versus off stimulation Unified Parkinson's Disease Rating Scale motor scores after 3 or 12 months of continuous stimulation and no improvements in the Unified Parkinson's Disease Rating Scale part III scores compared to baseline. In contrast, patients reported a significant reduction in falls in the on and off medication states both at 3 and 12 months after pedunculopontine nucleus deep-brain stimulation as captured in the Unified Parkinson's Disease Rating Scale part II scores. Our results suggest that pedunculopontine nucleus deep-brain stimulation may be effective in preventing falls in patients with advanced Parkinson's disease but that further evaluation of this procedure is required.

Young-Onset Parkinson's

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... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Diagnosis (Parkinson's Disease)

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Stages of Parkinson's

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Mobility (Parkinson's Disease)

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Symptoms of Parkinson's

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Living with Parkinson's

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Effects of parkinsonism on health status in welding exposed workers.

PubMed

Harris, Rachel C; Lundin, Jessica I; Criswell, Susan R; Hobson, Angela; Swisher, Laura M; Evanoff, Bradley A; Checkoway, Harvey; Racette, Brad A

2011-11-01

Previous studies suggest that welders frequently display parkinsonian signs, such as bradykinesia and tremor. Demonstrating that these parkinsonian findings are associated with reductions in quality of life (QoL) or health status could have important repercussions for worker safety and performance. Subjects included 394 active workers exposed to welding fumes and evaluated for parkinsonism by movement disorders experts in a worksite-based epidemiology study. Subjects were diagnosed with parkinsonism if the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) score was ≥15. All subjects completed a Parkinson's disease (PD) symptom questionnaire and the PDQ39, a widely used QoL and health status measure for PD. Total PDQ39 score and all subscores were greater in welders with parkinsonism than welders without parkinsonism, with the most significant differences observed for mobility, emotional well-being, and activities of daily living (ADL's). The PDQ39 scores for welding exposed workers with parkinsonism were similar to scores seen in a group of early PD patients. Parkinsonism in active, welding exposed workers is associated with reductions in health status and QoL affecting a broad range of categories and within the range seen in early PD. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mortalin inhibition in experimental Parkinson's disease.

PubMed

Chiasserini, Davide; Tozzi, Alessandro; de Iure, Antonio; Tantucci, Michela; Susta, Federica; Orvietani, Pier Luigi; Koya, Keizo; Binaglia, Luciano; Calabresi, Paolo

2011-08-01

Among heat shock proteins, mortalin has been linked to the pathogenesis of Parkinson's disease. In the present work a rat model of Parkinson's disease was used to analyze the expression of striatal proteins and, more specifically, mortalin expression. The possible involvement of mortalin in Parkinson's disease pathogenesis was further investigated by utilizing an electrophysiological approach and pharmacological inhibition of mortalin in both the physiological and the parkinsonian states. Proteomic analysis was used to investigate changes in striatal protein expression in the 6-hydroxydopamine rat model of Parkinson's disease. The electrophysiological effects of MKT-077, a rhodamine-123 analogue acting as an inhibitor of mortalin, were measured by field potential recordings from corticostriatal brain slices obtained from control, sham-operated, and 6-hydroxydopamine-denervated animals. Slices in the presence of rotenone, an inhibitor of mitochondrial complex I, were also analyzed. Proteomic analysis revealed downregulation of mortalin in the striata of 6-hydroxydopamine-treated rats in comparison with sham-operated animals. MKT-077 reduced corticostriatal field potential amplitude in physiological conditions, inducing membrane depolarization and inward current in striatal medium spiny neurons. In addition, we observed that concentrations of MKT-077 not inducing any electrophysiological effect in physiological conditions caused significant changes in striatal slices from parkinsonian animals as well as in slices treated with a submaximal concentration of rotenone. These findings suggest a critical link between mortalin function and mitochondrial activity in both physiological and pathological conditions mimicking Parkinson's disease. Copyright © 2011 Movement Disorder Society.

Hypothyroidism-induced Reversible Encephalopathy as a Cause of Aggravation of Parkinsonism and Myoclonus in Parkinson's Disease.

PubMed

Ehm, Gwanhee; Kim, Han-Joon; Jeon, Beomseok

2017-01-01

Myoclonus and encephalopathy are unusual in patients with Parkinson's disease (PD). We describe the case of a 59-year-old male with PD who developed myoclonus and encephalopathy. Underlying hypothyroidism was revealed after admission and treated with levothyroxine. Myoclonus and encephalopathy were completely resolved following thyroid hormone replacement. Hypothyroidism can cause reversible myoclonus and encephalopathy along with unusual aggravation of parkinsonism symptoms in patients with PD.

Parkinson's disease and periodontitis - the missing link? A review.

PubMed

Kaur, Tejaswani; Uppoor, Ashita; Naik, Dilip

2016-12-01

In this article an attempt has been made to postulate a possible link between Parkinson's disease and periodontal disease. Various systemic diseases such as cardiac disease, diabetes, renal diseases, low birth weight and Alzheimer's disease have been proposed to be linked with periodontal disease on the basis of systemic inflammation. Parkinson's disease is a chronic progressive neurodegenerative disorder with multifactorial aetiology. Until now, periodontal disease and Parkinson's disease has been linked only on the basis of poor motor and cognitive control in Parkinson's patient which leads to poor oral health maintenance. Evidence now suggests that chronic neuroinflammation is consistently associated with the pathophysiology of Parkinson's disease. Also, recently, systemic inflammation has been suggested as one of the contributing factors for neurodegeneration. Dental and medical literature especially those dealing with neurosciences were selected which highlighted the link between systemic inflammation and infection. So far there is no direct evidence implicating an effect of periodontitis in the pathogenesis of Parkinson's disease. To clarify this link, studies on population based case-control or cohort design are needed. This would be especially significant in the present era where there is paucity for preventive measures as far as a cognitive disorder such as Parkinson's disease is concerned. We cannot cure Parkinson's disease, but if in future this missing link is established, an attempt can be made to prevent it by tackling one of its possible contributors (periodontitis) for systemic inflammation by simple preventive oral hygiene measures. © 2015 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

Correlates of constipation in people with Parkinson's.

PubMed

Gage, H; Kaye, J; Kimber, A; Storey, L; Egan, M; Qiao, Y; Trend, P

2011-02-01

To investigate clinical, demographic and dietary factors associated with constipation in a sample of community dwelling people with Parkinson's disease, recruited through a specialist outpatient clinic. Partners/carers provided a convenience control group. Participants completed a baseline questionnaire (background information, diet and exercise, activities of daily living: mobility and manual dexterity, health-related quality of life (SF-12), stool frequency and characteristics, extent of concern due to constipation, laxative taking), and a four-week stool diary. The Rome criterion was used to determine constipation status. Multiple regression methods were used to explore the correlates of constipation. Baseline data were provided by 121 people with Parkinson's, (54 controls), of whom 73% (25%) met the Rome criterion. Prospective diary data from 106 people with Parkinson's (43 controls) showed lower proportions: 35% (7%) meeting the Rome criterion. Among all study subjects, i.e. Parkinson's patients and controls taken together, the presence of constipation is predicted by having Parkinson's disease (p = .003; odds ratio 4.80, 95% CI 1.64-14.04) and mobility score (p = .04; odds ratio 1.15, 95% CI 1.01-1.31), but not by dietary factors. Amongst people with Parkinson's constipation is predicted by number of medications (p = .027). Laxative taking masks constipation, and is significantly associated with wearing protection against bowel incontinence (p = .009; odds ratio 4.80, 95% CI: 1.48-15.52). Constipation is disease-related, not a lifestyle factor. More research is needed on optimal management and laxative use. Copyright © 2010 Elsevier Ltd. All rights reserved.

Parkinson's disease and α-synuclein expression.

PubMed

Devine, Michael J; Gwinn, Katrina; Singleton, Andrew; Hardy, John

2011-10-01

Genetic studies of Parkinson's disease over the last decade or more have revolutionized our understanding of this condition. α-Synuclein was the first gene to be linked to Parkinson's disease, and is arguably the most important: the protein is the principal constituent of Lewy bodies, and variation at its locus is the major genetic risk factor for sporadic disease. Intriguingly, duplications and triplications of the locus, as well as point mutations, cause familial disease. Therefore, subtle alterations of α-synuclein expression can manifest with a dramatic phenotype. We outline the clinical impact of α-synuclein locus multiplications, and the implications that this has for Parkinson's disease pathogenesis. Finally, we discuss potential strategies for disease-modifying therapies for this currently incurable disorder. Copyright © 2011 Movement Disorder Society.

Quantifying gait patterns in Parkinson's disease

NASA Astrophysics Data System (ADS)

Romero, Mónica; Atehortúa, Angélica; Romero, Eduardo

2017-11-01

Parkinson's disease (PD) is constituted by a set of motor symptoms, namely tremor, rigidity, and bradykinesia, which are usually described but not quantified. This work proposes an objective characterization of PD gait patterns by approximating the single stance phase a single grounded pendulum. This model estimates the force generated by the gait during the single support from gait data. This force describes the motion pattern for different stages of the disease. The model was validated using recorded videos of 8 young control subjects, 10 old control subjects and 10 subjects with Parkinson's disease in different stages. The estimated force showed differences among stages of Parkinson disease, observing a decrease of the estimated force for the advanced stages of this illness.

Decreased β-phenylethylamine in CSF in Parkinson's disease

PubMed Central

Zhou, G.; Shoji, H.; Yamada, S.; Matsuishi, T.

1997-01-01

OBJECTIVE—To determine the concentrations of β-phenylethylamine (PEA) in CSF in patients with Parkinson's disease, and to evaluate the relation between concentration of PEA in CSF and severity of Parkinson's disease.
METHODS—Using gas chromatography-chemical ionisation mass spectrometry, CSF concentrations of PEA were measured in 23 patients with Parkinson's disease (mean age, 64.0 (SD 8.2) years), of whom three were at Hoehn and Yahr stage II, 11 were at stage III, and nine were at stage IV. Comparison was made with eight patients with neuropathy (mean age, 57.0 (SD 19.2) years) and 12 controls without neurological disease (mean age, 57.6 (SD 4.8) years).
RESULTS—Concentrations of PEA in CSF in Parkinson's disease were significantly lower (mean 205 (SD 131) pg/ml) than in patients with peripheral neuropathy (433 (SD 254) pg/ml) and controls (387 (SD 194) pg/ml). The concentrations of PEA in CSF correlated negatively with Hoehn and Yahr stage (P<0.01).
CONCLUSIONS—There are decreased CSF concentrations of PEA in patients with Parkinson's disease.

 PMID:9416810

Autobiographical memory in Parkinson's disease: a retrieval deficit.

PubMed

Souchay, Celine; Smith, Sarah Jane

2013-09-01

This study examined the effects of providing cues to facilitate autobiographical memory retrieval in Parkinson's disease. Previous findings have shown that individuals with Parkinson's disease retrieve fewer specific autobiographical memories than older adult controls. These findings are clinically significant since the quality of autobiographical memory is linked to identity and sense of self. In the current study, 16 older adults with Parkinson's disease without dementia and 16 matched older adult controls were given 3 min in which to recall autobiographical memories associated with five different time periods and to give each memory a short title. Participants were later asked to retrieve the memories in three phases: firstly in a free recall phase; secondly in response to general cues (time periods) and finally in response to specific cues (the short titles previously given). The number of memories and the quality of the memory (general or specific) was recorded in each condition. Compared with matched older adult controls, the Parkinson's disease group was impaired in retrieving the memories that they had previously given in the free recall phase and in response to general cues. The performance of the group with Parkinson's disease was only equivalent to the older adults when they retrieved memories in response to self-generated cues. The findings are discussed in relation to theories of autobiographical memory and the neuropsychology of Parkinson's disease. © 2013 The British Psychological Society.

Genetic influences on cognitive decline in Parkinson's disease

PubMed Central

Morley, J.F.; Xie, S.X.; Hurtig, H.I.; Stern, M.B.; Colcher, A.; Horn, S.; Dahodwala, N.; Duda, J.E.; Weintraub, D.; Chen-Plotkin, A.S.; Van Deerlin, V.; Falcone, D.; Siderowf, A.

2012-01-01

Background The role of genetic factors in cognitive decline associated with Parkinson's disease is unclear. We examined whether variations in apolipoprotein E, microtubule-associated protein tau or catechol-O-methytransferase genotypes are associated with cognitive decline in Parkinson's disease. Methods We performed a prospective cohort study of 212 patients with a clinical diagnosis of Parkinson's disease. The primary outcome was change in Mattis Dementia Rating Scale version 2 score. Linear mixed-effects models and survival analysis were used to test for associations between genotypes and change in cognitive function over time. Results The ε4 allele of apoliporotein E was associated with more rapid decline (loss of 2.9 (95% CI, 1.7–4.1) more points/year, p<0.001) in total score and an increased risk of a ≥10 pointdrop during the follow-up period (HR 2.8, 95% CI 1.4–5.4, p=0.003). Microtubule-associated protein tau haplotype and catechol-O-methytransferase genotype were associated with measures of memory and attention, respectively, over the entire followup period but not with the overall rate of cognitive decline. Conclusion These results confirm and extend previously described genetic associations with cognitive decline in Parkinson's disease and imply that individual genes may exert effects on specific cognitive domains or at different disease stages. Carrying at least one apolipoprotein E ε4 allele is associated with more rapid cognitive decline in Parkinson's disease, supporting the idea of a component of shared etiology between Parkinson's disease dementia and Alzheimer disease. Clinically, these results suggest genotyping can provide information about the risk of future cognitive decline for Parkinson's disease patients. PMID:22344634

Physical therapy and occupational therapy in Parkinson's disease.

PubMed

Radder, Danique L M; Sturkenboom, Ingrid H; van Nimwegen, Marlies; Keus, Samyra H; Bloem, Bastiaan R; de Vries, Nienke M

2017-10-01

Current medical management is only partially effective in controlling the symptoms of Parkinson's disease. As part of comprehensive multidisciplinary care, physical therapy and occupational therapy aim to support people with Parkinson's disease in dealing with the consequences of their disease in daily activities. In this narrative review, we address the limitations that people with Parkinson's disease may encounter despite optimal medical management, and we clarify both the unique and shared approaches that physical therapists and occupational therapists can apply in treating these limitations.

Association between polychlorinated biphenyls and Parkinson's disease neuropathology.

PubMed

Hatcher-Martin, Jaime M; Gearing, Marla; Steenland, Kyle; Levey, Allan I; Miller, Gary W; Pennell, Kurt D

2012-10-01

Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson's disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson's disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson's disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson's disease patients. When stratified by sex, the female Parkinson's disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson's disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson's disease-related pathology. Furthermore, these data support epidemiological and laboratory studies

Parkinson disease. Unravelling the nonmotor mysteries of Parkinson disease.

PubMed

Chaudhuri, K Ray; Sauerbier, Anna

2016-01-01

Parkinson disease (PD) is now regarded as a mixed motor, nonmotor and multiorgan disorder rather than a pure movement disorder. Nonmotor symptoms (NMS) have underpinned this conceptual change, and new criteria for clinical and prodromal diagnosis of PD, incorporating a range of NMS, have recently been published.

Association of restless legs syndrome, pain, and mood disorders in Parkinson's disease.

PubMed

Rana, Abdul Qayyum; Qureshi, Abdul Rehman M; Rahman, Labiba; Jesudasan, Ajantha; Hafez, Kevin K; Rana, Mohammad A

2016-01-01

The objectives of the study were to analyze the association between Parkinson's disease and restless legs syndrome, and to explore the relationship between mood disorder comorbidity (anxiety and depression), pain, and restless legs syndrome. This study included 123 Parkinson's disease patients and 123 non-Parkinson's disease patients matched for age and gender, and evaluated for anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence. This was performed using semi-structured interviews and a neurological examination through the restless legs syndrome diagnostic criteria and the following inventories; Hospital Anxiety and Depression Scale, Brief Pain Inventory, and Pain Disability Index. Parkinson's disease patients had significantly greater anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence in comparison to controls. In addition, Parkinson's disease patients' comorbid for anxiety and depression had significantly greater pain severity, pain interference, and pain disability, but not RLS prevalence, in comparison to Parkinson's disease only, Parkinson's disease anxiety, and Parkinson's disease depression patients. Pain interference, pain severity, and pain disability is greater among Parkinson's disease patients with anxiety and depression, in comparison to Parkinson's disease patients without anxiety and depression. On the contrary, the prevalence of restless legs syndrome was not found to be relevant.

Gene Therapy for Parkinson's Disease

PubMed Central

Denyer, Rachel; Douglas, Michael R.

2012-01-01

Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field. PMID:22619738

Gene therapy for Parkinson's disease.

PubMed

Denyer, Rachel; Douglas, Michael R

2012-01-01

Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field.

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. © The Author(s) 2016.

Association between physical fitness, cardiovascular risk factors, and Parkinson's disease.

PubMed

Müller, Jan; Myers, Jonathan

2018-01-01

Objective Exercise is a cornerstone of therapy for Parkinson's disease. This study addressed the association between physical fitness and the onset of Parkinson's disease and association with cardiovascular risk factors. Patients and methods Male veterans ( N = 7347, 59.0 ± 11.2 years) from the Veterans Exercise Testing Study cohort were evaluated. Physical fitness was measured objectively by maximal exercise testing. Onset of Parkinson's disease was abstracted from the Veterans Affairs computerized patient records system. Results After a mean follow-up of 12.5 ± 6.3 years, a total of 94 (1.3%) developed Parkinson's disease. Incidence was 86 cases per 100,000 person-years. The strongest multivariate factors associated with incidence of Parkinson's disease were higher age (hazard ratio: 1.067, 95% confidence interval (CI): 1.043-1.093, p < .001), current smoking (hazard ratio: 0.511, 95% CI: 0.274-0.953, p = .035) and physical fitness (high vs. low: hazard ratio: 0.239, 95% CI: 0.079-0.725, p = .011). Compared with patients with no or only one of these risk factors, patients with two risk factors had a 3.7-fold ( p < .001) increased risk for incidence of Parkinson's disease; those with all three risk factors had a 7.8-fold ( p < .001) higher risk. Conclusions High physical fitness, current smoking and younger age were associated with a lower incidence of Parkinson's disease. These findings parallel those of several epidemiological studies focusing on physical activity and the onset of Parkinson's disease. Together, these observations provide strong support for recommending physical activity to diminish risk of Parkinson's disease.

Parkinson's Disease: Leucine-Rich Repeat Kinase 2 and Autophagy, Intimate Enemies

PubMed Central

Bravo-San Pedro, José M.; Gómez-Sánchez, Rubén; Pizarro-Estrella, Elisa; Niso-Santano, Mireia; González-Polo, Rosa A.; Fuentes Rodríguez, José M.

2012-01-01

Parkinson's disease is the second common neurodegenerative disorder, after Alzheimer's disease. It is a clinical syndrome characterized by loss of dopamine-generating cells in the substancia nigra, a region of the midbrain. The etiology of Parkinson's disease has long been through to involve both genetic and environmental factors. Mutations in the leucine-rich repeat kinase 2 gene cause late-onset Parkinson's disease with a clinical appearance indistinguishable from Parkinson's disease idiopathic. Autophagy is an intracellular catabolic mechanism whereby a cell recycles or degrades damage proteins and cytoplasmic organelles. This degradative process has been associated with cellular dysfunction in neurodegenerative processes including Parkinson's disease. We discuss the role of leucine-rich repeat kinase 2 in autophagy, and how the deregulations of this degradative mechanism in cells can be implicated in the Parkinson's disease etiology. PMID:22970411

Parkinson Disease: Treating Symptoms Unrelated to Muscle Movement

MedlinePlus

... Evidence-based Guideline for PATIENTS and their FAMILIES PARKINSON DISEASE: TREATING SYMPTOMS UNRELATED TO MUSCLE MOVEMENT This fact sheet may help you understand which therapies help Parkinson disease (PD) symptoms unrelated to muscle movement. Neurologists from ...

POLG1-related levodopa-responsive parkinsonism.

PubMed

Miguel, Rita; Gago, Miguel Fernandes; Martins, João; Barros, Pedro; Vale, José; Rosas, Maria José

2014-11-01

Parkinsonian features have been described in patients with POLG1 mutations. Notwithstanding, the clinical expression has been revealed heterogeneous and the response to dopaminergic treatment has been document in few cases. We aim to describe the longitudinal clinical features and the treatment response of three unrelated patients with neurodegenerative parkinsonism, preceded by PEO and SANDO syndromes, who harbor POLG1 mutations, including two novel mutations. It was documented a sustained response to levodopa, at 3 and 8 years of follow-up of parkinsonian syndrome, and reduced striatal dopamine uptake. We review the genotypic and phenotypic spectrum of POLG1-related parkinsonism. Our observations stimulate the debate around the role of mitochondrial DNA defects in the pathogenesis of neurodegenerative parkinsonism. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Daytime Napping, Nighttime Sleeping, and Parkinson Disease

PubMed Central

Gao, Jianjun; Huang, Xuemei; Park, Yikyung; Hollenbeck, Albert; Blair, Aaron; Schatzkin, Arthur; Chen, Honglei

2011-01-01

Preliminary evidence suggests that daytime sleepiness may predate clinical diagnosis of Parkinson disease. The authors examined daytime napping and nighttime sleeping durations, reported in 1996–1997 by 220,934 US NIH-AARP Diet and Health Study participants, in relation to Parkinson disease diagnoses at 3 clinical stages: established (cases diagnosed before 1995, n = 267), recent (1995–1999, n = 396), and prediagnostic (2000 and after, n = 770). Odds ratios and 95% confidence intervals were derived from multivariate logistic regression models. Longer daytime napping was associated with higher odds of Parkinson disease at all 3 clinical stages: the odds ratios comparing long nappers (>1 hour/day) with nonnappers were 3.9 (95% confidence interval: 2.8, 5.6) for established cases, 2.2 (95% confidence interval: 1.7, 3.0) for recent cases, and 1.5 (95% confidence interval: 1.2, 1.9) for prediagnostic cases. Further control for health status or nighttime sleeping duration attenuated the association for established cases but made little difference for recent or prediagnostic cases. In the nighttime sleeping analysis, a clear U-shaped association with Parkinson disease was observed for established cases; however, this association was attenuated markedly for recent cases and disappeared for prediagnostic cases. This study supports the notion that daytime sleepiness, but not nighttime sleeping duration, is one of the early nonmotor symptoms of Parkinson disease. PMID:21402730

Effects of Parkinsonism on Health Status in Welding Exposed Workers

PubMed Central

Harris, Rachel C.; Lundin, Jessica I.; Criswell, Susan R.; Hobson, Angela; Swisher, Laura M.; Evanoff, Bradley A.; Checkoway, Harvey; Racette, Brad A.

2011-01-01

Background Previous studies suggest that welders frequently display parkinsonian signs, such as bradykinesia and tremor. Demonstrating that these parkinsonian findings are associated with reductions in quality of life (QoL) or health status could have important repercussions for worker safety and performance. Methods Subjects included 394 active workers exposed to welding fumes and evaluated for parkinsonism by movement disorders experts in a worksite-based epidemiology study. Subjects were diagnosed with parkinsonism if the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) score was >15. All subjects completed a Parkinson’s disease (PD) symptom questionnaire and the PDQ39, a widely used QoL and health status measure for PD. Results Total PDQ39 score and all subscores were greater in welders with parkinsonism than welders without parkinsonism, with the most significant differences observed for mobility, emotional well-being, and activities of daily living (ADL’s). The PDQ39 scores for welding exposed workers with parkinsonism were similar to scores seen in a group of early PD patients. Conclusion Parkinsonism in active, welding exposed workers is associated with reductions in health status and QoL affecting a broad range of categories and within the range seen in early PD. PMID:21724446

Excessive daytime sleepiness in Parkinson disease: a SPECT study.

PubMed

Matsui, Hideaki; Nishinaka, Kazuto; Oda, Masaya; Hara, Narihiro; Komatsu, Kenichi; Kubori, Tamotsu; Udaka, Fukashi

2006-07-01

The underlying pathologic mechanism of excessive daytime sleepiness (EDS) in Parkinson disease and the relative contributions of brain function to this process are poorly understood. We compared brain perfusion images between patients with Parkinson disease and EDS and those without EDS using n-isopropyl-p-1231 iodoamphetamine single photon emission computed tomography. Clinical study. Sumitomo Hospital. Thirteen patients with Parkinson disease with EDS (EDS group) and 27 patients with Parkinson disease without EDS (no-EDS group) were studied. Whether or not each case had EDS was determined according to the response to the Epworth Sleepiness Scale: patients with an Epworth Sleepiness Scale score > or = 10 were included in the EDS group, and patients with an Epworth Sleepiness Scale score < or = 9 were included in the no-EDS group. There were significant hypoperfusions in the left parietal and temporal association cortex in the EDS group. In the multivariable logistic regression model, attention and decreased regional cerebral blood flow of the left parietal association cortex and right caudate and increased regional cerebral blood flow of the right thalamus were the independent and significant factors. The cortical hypofunction relative to hyperfunction of the brain stem may relate to EDS in Parkinson disease. This is the first imaging study about EDS in Parkinson disease, and further studies are required.

Rasagiline. Parkinson's disease: a simple me-too.

PubMed

2006-12-01

In Parkinson's disease, rasagiline, either alone (in early stage disease) or combined with levodopa, provides nothing new in terms of efficacy or tolerability. It is better to continue using one of the many anti-parkinson drugs with which we have more experience rather than expose patients to a new drug which offers no advantages.

Update in therapeutic strategies for Parkinson's disease.

PubMed

Kulisevsky, Jaime; Oliveira, Lais; Fox, Susan H

2018-05-08

To review recent advances in therapeutics for motor and nonmotor symptoms of Parkinson's disease. Neuroprotection remains a large area of investigation with preliminary safety data on alpha synuclein immunotherapy and glucagon-like peptide-1 agonists. Novel Monoamine Oxidase B and Caetchol-O-methyltransferase-inhibitors for motor fluctuations have shown benefit and are recently approved for clinical use. Long-acting amantadine has also been approved to reduce dyskinesia. Alternative delivery strategies (sublingual, inhaled) dopaminergics may prove useful for rapid reversal of Parkinson's disease motor symptoms. Advanced therapies (surgery and infusional therapies) continue to be useful in subgroups of patients for motor complications with improved safety and also benefit on some nonmotor symptoms, including neuropsychiatric issues. Specific therapeutics for cognition, swallowing, sleep, and mood disorders had moderate to limited benefits. Exercise-based therapy appears beneficial at all stages of Parkinson's disease. The motor symptoms of Parkinson's disease can be reasonably treated and managed. However, therapies to slow or prevent disease progression remain a focus of research. Despite increased studies, treating nonmotor symptoms remains a challenge and an ongoing priority.

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.

Pathological α-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients.

PubMed

Stokholm, Morten Gersel; Danielsen, Erik Hvid; Hamilton-Dutoit, Stephen Jacques; Borghammer, Per

2016-06-01

It has been hypothesized that Lewy pathology initiates in the enteric nervous system years prior to debut of clinical motor symptoms in Parkinson disease patients. This study investigates whether Lewy pathology is present in various gastrointestinal tract tissues from Parkinson disease patients in the prodromal phase. We used the Danish National Pathology Registry to identify archived paraffin-embedded tissue blocks from 57 Parkinson disease patients (98 blocks) and 90 control subjects (98 blocks). We employed 2 different immunohistochemistry techniques visualizing aggregated α-synuclein and phosphorylated α-synuclein. Thirty-nine Parkinson disease patients contributed tissues obtained in the prodromal disease phase, whereas 18 Parkinson disease patients contributed tissues obtained solely after Parkinson diagnosis. Prodromal tissues were obtained on average 7.0 years prior to diagnosis (range = 20 years to 4 months), and postdiagnosis tissue on average 2.8 years after diagnosis (range = 2 days to 18 years). Phosphorylated α-synuclein positivity was seen in 22 of 39 (56%) prodromal Parkinson disease subjects and 30 of 67 (45%) prodromal tissue blocks. These fractions were significantly higher compared to control subjects (p = 0.0001 and p = 0.0032, respectively). In contrast, no significant difference was seen in the positivity rate between prodromal Parkinson disease patients and controls when using the aggregated α-synuclein immunohistochemistry technique. We detected Lewy pathology in the gastrointestinal tract of patients up to 20 years prior to their Parkinson disease diagnosis. These findings are in accordance with a hypothesized prodromal disease phase spanning 10 to 20 years. Ann Neurol 2016;79:940-949. © 2016 American Neurological Association.

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

Baseline genetic associations in the Parkinson's Progression Markers Initiative (PPMI).

PubMed

Nalls, Mike A; Keller, Margaux F; Hernandez, Dena G; Chen, Lan; Stone, David J; Singleton, Andrew B

2016-01-01

The Parkinson's Progression Marker Initiative is an international multicenter study whose main goal is investigating markers for Parkinson's disease (PD) progression as part of a path to a treatment for the disease. This manuscript describes the baseline genetic architecture of this study, providing not only a catalog of disease-linked variants and mutations, but also quantitative measures with which to adjust for population structure. Three hundred eighty-three newly diagnosed typical PD cases, 65 atypical PD and 178 healthy controls, from the Parkinson's Progression Marker Initiative study have been genotyped on the NeuroX or Immunochip arrays. These data are freely available to all researchers interested in pursuing PD research within the Parkinson's Progression Marker Initiative. The Parkinson's Progression Marker Initiative represents a study population with low genetic heterogeneity. We recapitulate known PD associations from large-scale genome-wide association studies and refine genetic risk score models for PD predictability (area under the curve, ∼0.74). We show the presence of six LRRK2 p.G2019S and nine GBA p.N370S mutation carriers. The Parkinson's Progression Marker Initiative study and its genetic data are useful in studies of PD biomarkers. The genetic architecture described here will be useful in the analysis of myriad biological and clinical traits within this study. © 2015 International Parkinson and Movement Disorder Society.

Current management of Parkinson's disease.

PubMed

Salawu, F; Olokoba, A; Danburam, A

2010-01-01

Although Parkinson's disease (PD) is still incurable, a large number of different treatments have become available to improve the quality of life and physical and psychological morbidity, and its early treatment is of prime importance. This article reviews the current situation of PD. This review was based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. The subject headings and keywords used were Parkinson's disease and therapeutic advances. Only articles written in English were included.The management of PD has evolved rapidly over the last 10 years with the advent of new drugs and new classes of drugs, but the currently available treatment methods are all symptomatic ones. However, some of these may have marginal disease-modifying effects. Progress in manufacture of newer drugs has markedly improved the treatment of early PD; however, the management of advanced Parkinson's symptoms remains a challenge. Currently no treatment has been proven to slow the progression of PD. Although symptomatic therapy can provide benefit for many years, PD will eventually result in significant morbidity.

Tai Chi Exercise to Improve Non-Motor Symptoms of Parkinson's Disease.

PubMed

Nocera, Joe R; Amano, Shinichi; Vallabhajosula, Srikant; Hass, Chris J

2013-08-20

A substantial number of individuals with Parkinson's disease exhibit debilitating non-motor symptoms that decrease quality of life. To date, few treatment options exist for the non-motor symptomatology related to Parkinson's disease. The goal of this pilot investigation was to determine the effects of Tai Chi exercise on the non-motor symptomology in Parkinson's disease. Twenty-one individuals with Parkinson's disease were enrolled in a Tai Chi intervention (n=15) or a noncontact control group (n=6). Participants assigned to Tai Chi participated in 60-minute Tai Chi sessions three times per week, for 16 weeks. Pre and post measures included indices of cognitive-executive function including visuomotor tracking and attention, selective attention, working memory, inhibition, processing speed and task switching. Additionally, all participants were evaluated on the Parkinson's disease Questionnaire-39 and Tinetti's Falls Efficacy Scale. Results indicated that the Tai Chi training group had significantly better scores following the intervention than the control group on the Parkinson's disease Questionnaire-39 total score as well as the emotional well-being sub score. Trends for improvement were noted for the Tai Chi group on Digits Backwards, Tinetti's Falls Efficacy Scale, and the activities of daily living and communication sub scores of the Parkinson's disease Questionnaire-39. This research provides initial data that supports future studies to definitively establish efficacy of Tai Chi to improve non-motor features of Parkinson's disease.

Is cerebral vasomotor reactivity impaired in Parkinson disease?

PubMed

Hanby, Martha F; Panerai, Ronney B; Robinson, Thompson G; Haunton, Victoria J

2017-04-01

The ability of a blood vessel to change diameter in response to a change in carbon dioxide concentration is often referred to as vasomotor reactivity. This study aimed to determine whether vasomotor reactivity is impaired in patients with idiopathic Parkinson's Disease in comparison to healthy controls. Transcranial Doppler was used to measure cerebral blood flow velocity in the middle cerebral arteries at baseline and under hypocapnic conditions in 40 patients with idiopathic Parkinson's disease and 50 healthy controls. Vasomotor reactivity, assessed under hypocapnic conditions, is not impaired in patients with idiopathic Parkinson's Disease in comparison to healthy controls.

Doppler sonography characteristics of vertebrobasilar circulation in patients with Parkinson's disease.

PubMed

Vidović, Mirjana; Sinanović, Osman; Smajlović, Dzevdet; Burina, Adnan; Hudić, Josip

2008-08-01

The objective of the study was to analyze the doppler sonography findings of vertebrobasilar circulation (VB) in patients with Parkinson's disease. 40 patients were analyzed (25 men's and 15 women) with Parkinson's disease, average age was 61.9 years (SD=11.43), treated at the Clinic for Neurology in Tuzla. Device for doppler sonography was Multidop x 4. Doppler sonography findings of VB circulation were analyzed in order to computerized tomography (CT) findings of the brain (with or without ischemic lacunar lesions) and in order to presence of postural disturbances as one of dominant Parkinson's disease symptoms during actual hospitalization. Our results suggest that vertebrobasilar insufficiency is more frequent in patients with Parkinson's disease (no matter of type) and postural disturbances as a dominant symptom comparing to group of Parkinson's disease patients without postural disturbances. These results implicate the importance of doppler sonography findings of vertebrobasilar circulation in patients with Parkinson's disease and possibility of considering role of vertebrobasilar insufficiency in development of postural disturbances.

Office-Based Screening for Dementia in Parkinson Disease: The Montreal Parkinson Risk of Dementia Scale in 4 Longitudinal Cohorts.

PubMed

Dawson, Benjamin K; Fereshtehnejad, Seyed-Mohammad; Anang, Julius B M; Nomura, Takashi; Rios-Romenets, Silvia; Nakashima, Kenji; Gagnon, Jean-François; Postuma, Ronald B

2018-06-01

Parkinson disease dementia dramatically increases mortality rates, patient expenditures, hospitalization risk, and caregiver burden. Currently, predicting Parkinson disease dementia risk is difficult, particularly in an office-based setting, without extensive biomarker testing. To appraise the predictive validity of the Montreal Parkinson Risk of Dementia Scale, an office-based screening tool consisting of 8 items that are simply assessed. This multicenter study (Montreal, Canada; Tottori, Japan; and Parkinson Progression Markers Initiative sites) used 4 diverse Parkinson disease cohorts with a prospective 4.4-year follow-up. A total of 717 patients with Parkinson disease were recruited between May 2005 and June 2016. Of these, 607 were dementia-free at baseline and followed-up for 1 year or more and so were included. The association of individual baseline scale variables with eventual dementia risk was calculated. Participants were then randomly split into cohorts to investigate weighting and determine the scale's optimal cutoff point. Receiver operating characteristic curves were calculated and correlations with selected biomarkers were investigated. Dementia, as defined by Movement Disorder Society level I criteria. Of the 607 patients (mean [SD] age, 63.4 [10.1]; 376 men [62%]), 70 (11.5%) converted to dementia. All 8 items of the Montreal Parkinson Risk of Dementia Scale independently predicted dementia development at the 5% significance level. The annual conversion rate to dementia in the high-risk group (score, >5) was 14.9% compared with 5.8% in the intermediate group (score, 4-5) and 0.6% in the low-risk group (score, 0-3). The weighting procedure conferred no significant advantage. Overall predictive validity by the area under the receiver operating characteristic curve was 0.877 (95% CI, 0.829-0.924) across all cohorts. A cutoff of 4 or greater yielded a sensitivity of 77.1% (95% CI, 65.6-86.3) and a specificity of 87.2% (95% CI, 84.1-89.9), with a

Elective Thoracolumbar Spine Fusion Surgery in Patients with Parkinson Disease.

PubMed

Puvanesarajah, Varun; Jain, Amit; Qureshi, Rabia; Carstensen, S Evan; Tyger, Rosemarie; Hassanzadeh, Hamid

2016-12-01

Few data are available concerning clinical outcomes in patients with Parkinson disease who undergo elective thoracolumbar spine fusion surgery. The goal of this study is to elucidate complication and revision rates after posterior thoracolumbar fusion surgery in patients with Parkinson disease, with a focus on how Parkinson disease modifies these rates. The PearlDiver database (2005-2012) was queried for patients who underwent posterior approach thoracolumbar fusion from 2006 to 2011. Cohorts of patients with a previous diagnosis of Parkinson disease (n = 4816) and without (n = 280,702) were compared. Multivariate analysis that included various comorbidities and demographics was used to calculate effects of Parkinson disease on development of postoperative infection and major medical complications within 90 days and revision surgery within 1 year. For analyses, significance was set at P < 0.001. Major medical complications were observed in 545 patients (11.3%) for 90 days after the index procedure. Postoperative infection was noted in 91 patients (1.9%) within 90 days, and revision surgeries were performed in 250 patients (5.2%) within 1 year. Multivariate analysis showed that Parkinson disease was significantly associated with an increased risk for medical complications (adjusted odds ratio, 1.22; 95% confidence interval, 1.11-1.34; P < 0.001) and revision surgery (adjusted odds ratio, 1.70; 95% confidence interval, 1.49-1.93; P < 0.001), but not postoperative infection (P = 0.02). Patients with Parkinson disease are more likely to require revision surgery and have higher rates of adverse medical events postoperatively. Patients with Parkinson disease should be appropriately selected to ensure favorable clinical outcomes. Copyright © 2016. Published by Elsevier Inc.

Reduced glucocerebrosidase is associated with increased α-synuclein in sporadic Parkinson's disease.

PubMed

Murphy, Karen E; Gysbers, Amanda M; Abbott, Sarah K; Tayebi, Nahid; Kim, Woojin S; Sidransky, Ellen; Cooper, Antony; Garner, Brett; Halliday, Glenda M

2014-03-01

Heterozygous mutations in GBA1, the gene encoding lysosomal glucocerebrosidase, are the most frequent known genetic risk factor for Parkinson's disease. Reduced glucocerebrosidase and α-synuclein accumulation are directly related in cell models of Parkinson's disease. We investigated relationships between Parkinson's disease-specific glucocerebrosidase deficits, glucocerebrosidase-related pathways, and α-synuclein levels in brain tissue from subjects with sporadic Parkinson's disease without GBA1 mutations. Brain regions with and without a Parkinson's disease-related increase in α-synuclein levels were assessed in autopsy samples from subjects with sporadic Parkinson's disease (n = 19) and age- and post-mortem delay-matched controls (n = 10). Levels of glucocerebrosidase, α-synuclein and related lysosomal and autophagic proteins were assessed by western blotting. Glucocerebrosidase enzyme activity was measured using a fluorimetric assay, and glucocerebrosidase and α-synuclein messenger RNA expression determined by quantitative polymerase chain reaction. Related sphingolipids were analysed by mass spectrometry. Multivariate statistical analyses were performed to identify differences between disease groups and regions, with non-parametric correlations used to identify relationships between variables. Glucocerebrosidase protein levels and enzyme activity were selectively reduced in the early stages of Parkinson's disease in regions with increased α-synuclein levels although limited inclusion formation, whereas GBA1 messenger RNA expression was non-selectively reduced in Parkinson's disease. The selective loss of lysosomal glucocerebrosidase was directly related to reduced lysosomal chaperone-mediated autophagy, increased α-synuclein and decreased ceramide. Glucocerebrosidase deficits in sporadic Parkinson's disease are related to the abnormal accumulation of α-synuclein and are associated with substantial alterations in lysosomal chaperone-mediated autophagy

Drugs of abuse and Parkinson's disease.

PubMed

Mursaleen, Leah R; Stamford, Jonathan A

2016-01-04

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Conditions Related to Parkinson's

MedlinePlus

... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

What Is Parkinson's Disease?

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... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Conditions that Mimic Parkinson's

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... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Parkinson's Foundation: For Caregivers

MedlinePlus

... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Parkinson's Disease Foundation News

MedlinePlus

... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Mirror movements in parkinsonism: evaluation of a new clinical sign

PubMed Central

Espay, A; Li, J; Johnston, L; Chen, R; Lang, A

2005-01-01

Background: Mirror movements (MM) are not widely appreciated in parkinsonism and no report has evaluated this clinical sign in detail. Objectives: To define the parkinsonian clinical features associated with MM in patients with early, asymmetric parkinsonism. Methods: Twenty seven patients with early Parkinson's disease were evaluated using a standardised videotaping protocol. MM were scored from blinded video assessment using a clinical scale that rates the amplitude, distribution, and proportion of mirroring in the less affected limb. Parkinsonian features were combined into axial and lateralised scores using related items of the Unified Parkinson's Disease Rating Scale. Results: MM were present in 24 of 27 patients. There was a significant linear correlation between the degree of asymmetry of motor deficits and MM on the less affected side. The effect of asymmetry was greater when the proportional rather than the absolute motor difference between sides was largest. Asymmetry in leg rigidity was the most important examination feature in the prediction of contralateral foot mirroring. Conclusions: MM are a clinical feature of the unaffected or less affected side in mild asymmetric parkinsonism. Their presence may be a useful clinical finding in early parkinsonism. PMID:16170075

Visual short-term memory deficits associated with GBA mutation and Parkinson's disease.

PubMed

Zokaei, Nahid; McNeill, Alisdair; Proukakis, Christos; Beavan, Michelle; Jarman, Paul; Korlipara, Prasad; Hughes, Derralynn; Mehta, Atul; Hu, Michele T M; Schapira, Anthony H V; Husain, Masud

2014-08-01

Individuals with mutation in the lysosomal enzyme glucocerebrosidase (GBA) gene are at significantly high risk of developing Parkinson's disease with cognitive deficit. We examined whether visual short-term memory impairments, long associated with patients with Parkinson's disease, are also present in GBA-positive individuals-both with and without Parkinson's disease. Precision of visual working memory was measured using a serial order task in which participants observed four bars, each of a different colour and orientation, presented sequentially at screen centre. Afterwards, they were asked to adjust a coloured probe bar's orientation to match the orientation of the bar of the same colour in the sequence. An additional attentional 'filtering' condition tested patients' ability to selectively encode one of the four bars while ignoring the others. A sensorimotor task using the same stimuli controlled for perceptual and motor factors. There was a significant deficit in memory precision in GBA-positive individuals-with or without Parkinson's disease-as well as GBA-negative patients with Parkinson's disease, compared to healthy controls. Worst recall was observed in GBA-positive cases with Parkinson's disease. Although all groups were impaired in visual short-term memory, there was a double dissociation between sources of error associated with GBA mutation and Parkinson's disease. The deficit observed in GBA-positive individuals, regardless of whether they had Parkinson's disease, was explained by a systematic increase in interference from features of other items in memory: misbinding errors. In contrast, impairments in patients with Parkinson's disease, regardless of GBA status, was explained by increased random responses. Individuals who were GBA-positive and also had Parkinson's disease suffered from both types of error, demonstrating the worst performance. These findings provide evidence for dissociable signature deficits within the domain of visual short

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…

▼ Safinamide for Parkinson's disease.

PubMed

2018-05-01

▼ Safinamide (Xadago - Zambon S.p.A) is a monoamine-oxidase B (MAO-B) inhibitor licensed as add-on therapy for people with idiopathic Parkinson's disease who are experiencing motor fluctuations with levodopa. 1 Currently there is no cure for Parkinson's disease and drugs are used to reduce motor symptoms and improve daily activities. 2,3 Here, we review the evidence for this MAO-B inhibitor. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Metabolic Imaging in Parkinson Disease.

PubMed

Meles, Sanne K; Teune, Laura K; de Jong, Bauke M; Dierckx, Rudi A; Leenders, Klaus L

2017-01-01

This review focuses on recent human 18 F-FDG PET studies in Parkinson disease. First, an overview is given of the current analytic approaches to metabolic brain imaging data. Next, we discuss how 18 F-FDG PET studies have advanced understanding of the relation between distinct brain regions and associated symptoms in Parkinson disease, including cognitive decline. In addition, the value of 18 F-FDG PET studies in differential diagnosis, identifying prodromal patients, and the evaluation of treatment effects are reviewed. Finally, anticipated developments in the field are addressed. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

The emerging science of precision medicine and pharmacogenomics for Parkinson's disease.

PubMed

Payami, Haydeh

2017-08-01

Current therapies for Parkinson's disease are problematic because they are symptomatic and have adverse effects. New drugs have failed in clinical trials because of inadequate efficacy. At the core of the problem is trying to make one drug work for all Parkinson's disease patients, when we know this premise is wrong because (1) Parkinson's disease is not a single disease, and (2) no two individuals have the same biological makeup. Precision medicine is the goal to strive for, but we are only at the beginning stages of building the infrastructure for one of the most complex projects in the history of science, and it will be a long time before Parkinson's disease reaps the benefits. Pharmacogenomics, a cornerstone of precision medicine, has already proven successful for many conditions and could also propel drug discovery and improve treatment for Parkinson's disease. To make progress in the pharmacogenomics of Parkinson's disease, we need to change course from small inconclusive candidate gene studies to large-scale rigorously planned genome-wide studies that capture the nuclear genome and the microbiome. Pharmacogenomic studies must use homogenous subtypes of Parkinson's disease or apply the brute force of statistical power to overcome heterogeneity, which will require large sample sizes achievable only via internet-based methods and electronic databases. Large-scale pharmacogenomic studies, together with biomarker discovery efforts, will yield the knowledge necessary to design clinical trials with precision to alleviate confounding by disease heterogeneity and interindividual variability in drug response, two of the major impediments to successful drug discovery and effective treatment. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Parkinson's disease in China.

PubMed

Tian, You-yong; Tang, Cui-ju; Wu, Jie; Zhou, Jun-shan

2011-02-01

Paralysis agitans was first documented in 1817 by James Parkinson, and therefore the syndrome was named Parkinson's disease (PD). In fact, as early as more than 2000 years ago, the clinical manifestations of this disease have been described in Chinese medicine classics, such as the "Huangdi Neijing (Yellow Emperor's Internal Classic)" and "Zhong Zang Jing (Hua's Zhong Zang Classic)." In recent years, especially in the past 30 years after reform and opening-up, PD has drawn a lot of attention by Chinese scholars. Although great progress in the studies of PD has been made in recent years, the gap between China and western countries still exists. In this review, we concentrate on the main progress made in epidemic characteristics, etiology, diagnosis and management of PD in China.

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

PubMed Central

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

2012-01-01

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

Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

PubMed Central

Gwinn, Katrina; David, Karen K; Swanson-Fischer, Christine; Albin, Roger; Hillaire-Clarke, Coryse St; Sieber, Beth-Anne; Lungu, Codrin; Bowman, F DuBois; Alcalay, Roy N; Babcock, Debra; Dawson, Ted M; Dewey, Richard B; Foroud, Tatiana; German, Dwight; Huang, Xuemei; Petyuk, Vlad; Potashkin, Judith A; Saunders-Pullman, Rachel; Sutherland, Margaret; Walt, David R; West, Andrew B; Zhang, Jing; Chen-Plotkin, Alice; Scherzer, Clemens R; Vaillancourt, David E; Rosenthal, Liana S

2017-01-01

Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset. PMID:28644039

Parkinson's disease: a population-based investigation of life satisfaction and employment.

PubMed

Gustafsson, Helena; Nordström, Peter; Stråhle, Stefan; Nordström, Anna

2015-01-01

To investigate relationships between individuals' socioeconomic situations and quality of life in working-aged subjects with Parkinson's disease. A population-based cohort comprising 1,432 people with Parkinson's disease and 1,135 matched controls, who responded to a questionnaire. Logistic regression analysis was performed to identify factors associated with life satisfaction and likelihood of employment. In multivariate analyses, Parkinson's disease was associated with an increased risk of dissatisfaction with life (odds ratio (OR) = 5.4, 95% confidence interval (95% CI) = 4.2-7.1) and reduced likelihood of employment (OR = 0.30, 95% CI = 0.25-0.37). Employers' support was associated with greater likelihood of employment (p < 0.001). Twenty-four percent of people with Parkinson's disease for ≥ 10 years remained employed and 6% worked full-time. People with Parkinson's disease also more frequently experienced work demands that exceeded their capacity; this factor and unemployment independently correlated with greater risk of dissatisfaction with life (both p < 0.05). People with Parkinson's disease have an increased risk of dissatisfaction with life. Employment situation is important for general life satisfaction among working-aged individuals. People with Parkinson's disease appear to find it difficult to meet the challenge of achieving a balanced employment situation.

Progressive parkinsonism in boxers.

PubMed

Friedman, J H

1989-05-01

Parkinsonism associated with boxing has attracted recent media attention, yet little has been written about it in the medical literature. This report presents a typical case with a review of the literature.

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. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

Imaging Amyloidopathy in Parkinson Disease and Parkinsonian Dementia Syndromes.

PubMed

Frey, Kirk A; Petrou, Myria

2015-02-01

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

Preprohypocretin polymorphisms in Parkinson disease patients reporting "sleep attacks".

PubMed

Rissling, Ida; Körner, Yvonne; Geller, Frank; Stiasny-Kolster, Karin; Oertel, Wolfgang H; Möller, J Carsten

2005-07-01

Previously, we found a significant association between the dopamine D2 receptor gene polymorphism Taq IA and sudden onset of sleep in patients with Parkinson disease. Here we evaluated the association between the preprohypocretin (-909T/C), (-22C/T), and (-20C/A) polymorphisms and sudden onset of sleep in the same population of patients with Parkinson disease. We conducted an association study analyzing the distribution of preprohypocretin polymorphisms in Germanic, caucasian Parkinson disease patients with and without sudden onset of sleep, matched according to drug therapy, disease duration, sex, and age. Movement disorders section at a university hospital. 132 Parkinson disease patients with sudden onset of sleep and 132 Parkinson disease patients without sudden onset of sleep. Blood samples were taken from each participant and used for DNA extraction. Polymorphisms were analyzed by established polymerase chain reaction protocols or direct sequencing. The variant allele T of the (-909T/C) preprohypocretin polymorphism was more commonly found in Parkinson disease patients with sudden onset of sleep. Statistical analysis showed that there were significant differences in the genotype (P = .024) and allele (P = .018) distribution between both groups. For heterozygous and homozygous carriers of allele T, the genotype relative-risk estimates for the presence of sudden onset of sleep were 2.01 (95% confidence interval: 0.76-5.34) and 2.81 (95% confidence interval: 1.09-7.25), respectively. Our results show a significant association between the (-909T/C) preprohypocretin polymorphism and sudden onset of sleep in Parkinson disease. However, we could not demonstrate any interaction between the Taq IA and (-909T/C) polymorphisms with respect to the occurrence of sudden onset of sleep, suggesting that multiple genetic factors may contribute to the pathogenesis of this phenomenon.

Aged monkeys as a partial model for Parkinson's disease

PubMed Central

Hurley, P.J.; Elsworth, J.D.; Whittaker, M.C.; Roth, R.H.; Redmond, D.E.

2011-01-01

Parkinson's Disease (PD) and the natural aging process share a number of biochemical mechanisms, including reduced function of dopaminergic systems. The present study aims to determine the extent that motor and behavioral changes in aged monkeys resemble parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The behavioral and physiological changes in PD are believed to result largely from selective depletion of dopamine in the nigrostriatal system. In the present study, ten aged female monkeys were compared with three groups: 9 untreated young adult female monkeys, 10 young adult male monkeys and 13 older male monkeys that had been exposed to MPTP. Trained observers, blind as to age and drug condition and without knowledge of the hypotheses, scored the monkeys using the Parkinson's factor score (Parkscore), which has been validated by a high correlation with post mortem striatal dopamine (DA) concentrations. The aged animals had higher scores on the Parkscore compared with the young adults, with most of its component behavioral items showing significance (tremor, eating problems, delayed initiation of movement, and poverty of movement). L-Dopa and DA-agonists did not clearly reverse the principal measure of parkinsonism. DA concentrations post mortem were 63% lower in 3 aged monkeys in the ventral putamen compared with 4 young adults, with greater reductions in putamen than in caudate (45%). We conclude that aged monkeys, unexposed to MPTP, show a similar profile of parkinsonism to that seen after the neurotoxin exposure to MPTP in young adult monkeys. The pattern of greater DA depletion in putamen than in caudate in aged monkeys is the same as in human Parkinson's disease and contrasts with the greater depletion in caudate seen after MPTP. Aged monkeys of this species reflect many facets of Parkinson's disease, but like older humans do not improve with standard dopamine replacement pharmacotherapies. PMID:21620883

Predictive risk factors for chronic low back pain in Parkinson's disease.

PubMed

Ozturk, Erhan Arif; Kocer, Bilge Gonenli

2018-01-01

Although previous studies have reported that the prevalence of low back pain in Parkinson's disease was over 50% and low back pain was often classified as chronic, risk factors of chronic low back pain have not been previously investigated. The aim of this study was to determine the predictive risk factors of chronic low back pain in Parkinson's disease. One hundred and sixty-eight patients with Parkinson's disease and 179 controls were consecutively included in the study. Demographic data of the two groups and disease characteristics of Parkinson's disease patient group were recorded. Low back pain lasting for ≥3 months was evaluated as chronic. Firstly, the bivariate correlations were calculated between chronic low back pain and all possible risk factors. Then, a multivariate regression was used to evaluate the impact of the predictors of chronic low back pain. The frequency of chronic low back pain in Parkinson's disease patients and controls were 48.2% and 26.7%, respectively (p < 0.001). The predictive risk factors of chronic low back pain in Parkinson's disease were general factors including age (odds ratio = 1.053, p = 0.032) and Hospital Anxiety and Depression Scale - Depression subscore (odds ratio = 1.218, p = 0.001), and Parkinson's disease-related factors including rigidity (odds ratio = 5.109, p = 0.002) and posture item scores (odds ratio = 5.019, p = 0.0001). The chronic low back pain affects approximately half of the patients with Parkinson's disease. Prevention of depression or treatment recommendations for managing depression, close monitoring of anti- parkinsonian medication to keep motor symptoms under control, and attempts to prevent, correct or reduce abnormal posture may help reduce the frequency of chronic low back pain in Parkinson's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

ATP13A2 variability in Parkinson disease

PubMed Central

Vilariño-Güell, Carles; Soto, Alexandra I.; Lincoln, Sarah J.; Yahmed, Samia Ben; Kefi, Mounir; Heckman, Michael G.; Hulihan, Mary M.; Chai, Hua; Diehl, Nancy N.; Amouri, Rim; Rajput, Alex; Mash, Deborah C.; Dickson, Dennis W.; Middleton, Lefkos T.; Gibson, Rachel A.; Hentati, Faycal; Farrer, Matthew J.

2008-01-01

Recessively inherited mutations in ATP13A2 result in Kufor-Rakeb syndrome, whereas genetic variability and elevated ATP13A2 expression have been implicated in Parkinson disease (PD). Given this background, ATP13A2 was comprehensively assessed to support or refute its contribution to PD. Sequencing of ATP13A2 exons and intron-exon boundaries was performed in 89 probands with familial parkinsonism from Tunisia. The segregation of mutations with parkinsonism was subsequently assessed within pedigrees. The frequency of genetic variants and evidence for association was also examined in 240 patients with non-familial PD and 372 healthy controls. ATP13A2 mRNA expression was also quantified in brain tissues from 38 patients with non-familial PD and 38 healthy subjects from the US. Sequencing analysis revealed 37 new variants; seven missense, six silent and 24 that were noncoding. However, no single ATP13A2 mutation segregated with familial parkinsonism in either a dominant or recessive manner. Four markers showed marginal association with non-familial PD, prior to correction for multiple testing. ATP13A2 mRNA expression was marginally decreased in PD brains compared with tissue from control subjects. In conclusion, neither ATP13A2 genetic variability nor quantitative gene expression in brain appears to contribute to familial parkinsonism or non-familial PD. PMID:19085912

Bisphenol A glucuronidation in patients with Parkinson's disease.

PubMed

Landolfi, Annamaria; Troisi, Jacopo; Savanelli, Maria Cristina; Vitale, Carmine; Barone, Paolo; Amboni, Marianna

2017-12-01

Bisphenol A (BPA) is a widely distributed estrogen-mimetic molecule, with well-established effects on the dopaminergic system. It can be found in canned food, dental sealants, thermal paper, etc. BPA undergoes liver conjugation with glucuronic acid and is subsequently excreted in the urine. In the present study we quantified the concentration of free and conjugated Bisphenol A in blood of patients affected by Parkinson Disease, using their spouses as controls. An interview was performed to determine possible confounders in BPA exposure. Free and conjugated BPA were quantified by gas chromatography coupled with mass spectrometry. Parkinson's Disease patients carried a statistically significant lower amount of conjugated Bisphenol A compared to controls. The two populations were mostly homogeneous in terms of exposure to possible Bisphenol A sources. The only exceptions were exposure to canned tuna and canned tomatoes PD patients consumed significantly more of both (p<0.05). Moreover, no difference in Bisphenol A glucuronidation was found after stratification by typology of anti-Parkinson's drug taken and after conversion to the Levodopa Equivalent Daily Dose. BPA glucuronidation was decreased in patients with Parkinson disease. The possible unique mechanisms underlying Bisphenol A metabolism in PD patients deserve further elucidation. Moreover, further study is needed to assess a possible BPA role in Parkinson's Disease pathogenesis, due to its documented dopaminergic toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Caring for the student with wolff-Parkinson-white syndrome.

PubMed

Prenni, Patricia G

2009-10-01

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 with the condition. Prophylactic treatments, as well as surgical intervention to permanently block the extra pathway, are options for people with Wolff-Parkinson-White syndrome. Tachycardia associated with Wolff-Parkinson-White syndrome can occur occasionally even when prophylactic treatment is administered. School nurses must know how to properly assess and treat episodes of tachycardia that may occur in the school setting. With proper education, school nurses can help provide a safe school environment for students with Wolff-Parkinson-White syndrome and promote successful academic achievement.

[Physical therapy for parkinson's disease].

PubMed

Hubert, M

2011-09-01

Parkinson's disease is a complex neurologic and progressive incapacitating disease. Parkinson's disease severely threatens the quality of live and the number of patients worldwide is expected to rise considerably in the coming decade due to aging of the population. Even with optimal medical management using drugs or neurosurgery, patients are faced with progressively increasing impairments (e.g. in speech, mental and movement related functions), and restrictions in participation (e.g. domestic life and social activities). Physical therapy is often prescribed next to medical treatment but there is a lack of uniform treatment. A systematic literature search for guidelines, systematic reviews, trials, and expert opinions lead to a better understanding. The key question: Is physiotherapy able to optimally treat the Parkinson's disease symptoms? In which way, how and on which scientific bases can the physiotherapist participate to improve autonomy and to help them living independently and avoid, as long as possible, institutionalization? This article has integrated clinical research findings to provide clinicians with an overview to physical therapist management of disorders in people with Parkinson's disease. An Evidence-Based Physical Therapy Guideline providing practice recommendations was developed by the Royal Dutch Society for Physical Therapy (KNGF). Evidence from research was supplemented with clinical expertise and patients values. Randomized clinical trials reflect specific core areas of physical therapy, that is, transfer, posture, balance, reaching and grasping, gait and physical condition. Another aspect is that of educating patients (as well as their partners and family) about the disease process and the benefits of exercise therapy. Alternative therapies can be helpful like Tai Chi, virtual games, dancing, yoga, ball games for example.

Swallowing disorders in Parkinson's disease.

PubMed

Mamolar Andrés, Sandra; Santamarina Rabanal, María Liliana; Granda Membiela, Carla María; Fernández Gutiérrez, María José; Sirgo Rodríguez, Paloma; Álvarez Marcos, César

Parkinson's disease is a type of chronic neurodegenerative pathology with a typical movement pattern, as well as different, less studied symptoms such as dysphagia. Disease-related disorders in efficacy or safety in the process of swallowing usually lead to malnutrition, dehydration or pneumonias. The aim of this study was identifying and analyzing swallowing disorders in Parkinson's disease. The initial sample consisted of 52 subjects with Parkinson's disease to whom the specific test for dysphagia SDQ was applied. Nineteen participants (36.5%) with some degree of dysphagia in the SDQ test were selected to be evaluated by volume-viscosity clinical exploration method and fiberoptic endoscopic evaluation of swallowing. Disorders in swallowing efficiency and safety were detected in 94.7% of the selected sample. With regards to efficiency, disorders were found in food transport (89.5%), insufficient labial closing (68.4%) and oral residues (47.4%), relating to duration of ingestion. Alterations in security were also observed: pharynx residues (52.7%), coughing (47.4%), penetration (31.64%), aspiration and decrease of SaO 2 (5.3%), relating to the diagnosis of respiratory pathology in the previous year. The SDQ test detected swallowing disorders in 36.5% of the subjects with Parkinson's disease. Disorders in swallowing efficiency and safety were demonstrated in 94.7% of this subset. Disorders of efficiency were more frequent than those of safety, establishing a relationship with greater time in ingestion and the appearance of respiratory pathology and pneumonias. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

Apathy and noradrenaline: silent partners to mild cognitive impairment in Parkinson's disease?

PubMed

Loued-Khenissi, Leyla; Preuschoff, Kerstin

2015-08-01

Mild cognitive impairment (MCI) is a comorbid factor in Parkinson's disease. The aim of this review is to examine the recent neuroimaging findings in the search for Parkinson's disease MCI (PD-MCI) biomarkers to gain insight on whether MCI and specific cognitive deficits in Parkinson's disease implicate striatal dopamine or another system. The evidence implicates a diffuse pathophysiology in PD-MCI rather than acute dopaminergic involvement. On the one hand, performance in specific cognitive domains, notably in set-shifting and learning, appears to vary with dopaminergic status. On the other hand, motivational states in Parkinson's disease along with their behavioral and physiological indices suggest a noradrenergic contribution to cognitive deficits in Parkinson's disease. Finally, Parkinson's disease's pattern of neurodegeneration offers an avenue for continued research in nigrostriatal dopamine's role in distinct behaviors, as well as the specification of dorsal and ventral striatal functions. The search for PD-MCI biomarkers has employed an array of neuroimaging techniques, but still yields divergent findings. This may be due in part to MCI's broad definition, encompassing heterogeneous cognitive domains, only some of which are affected in Parkinson's disease. Most domains falling under the MCI umbrella include fronto-dependent executive functions, whereas others, notably learning, rely on the basal ganglia. Given the deterioration of the nigrostriatal dopaminergic system in Parkinson's disease, it has been the prime target of PD-MCI investigation. By testing well defined cognitive deficits in Parkinson's disease, distinct functions can be attributed to specific neural systems, overcoming conflicting results on PD-MCI. Apart from dopamine, other systems such as the neurovascular or noradrenergic systems are affected in Parkinson's disease. These factors may be at the basis of specific facets of PD-MCI for which dopaminergic involvement has not been conclusive

Dopa-decarboxylase gene polymorphisms affect the motor response to L-dopa in Parkinson's disease.

PubMed

Devos, David; Lejeune, Stéphanie; Cormier-Dequaire, Florence; Tahiri, Khadija; Charbonnier-Beaupel, Fanny; Rouaix, Nathalie; Duhamel, Alain; Sablonnière, Bernard; Bonnet, Anne-Marie; Bonnet, Cecilia; Zahr, Noel; Costentin, Jean; Vidailhet, Marie; Corvol, Jean-Christophe

2014-02-01

In Parkinson's disease (PD), the response to L-dopa is highly variable and unpredictable. The major pathway for dopamine synthesis from L-dopa is decarboxylation by aromatic L-amino acid decarboxylase (AAAD, encoded by the DDC gene). To determine the motor response to L-dopa in PD patients as a function of the DDC gene promoter polymorphisms (rs921451 T > C polymorphism (DDC(T/C)) and rs3837091 AGAG del (DDC(AGAG/-))). Thirty-three Caucasian PD patients underwent an acute l-dopa challenge together with the peripheral AAAD inhibitor benserazide and were genotyped for rs921451 and rs3837091. The primary efficacy criterion was the motor response to L-dopa, as estimated by the area under the curve for the change in the Unified Parkinson's Disease Rating Scale part III (UPDRS) score relative to baseline (AUCΔUPDRS) in the 4 h following L-dopa administration. Secondary endpoints were pharmacokinetic parameters for plasma levels of L-dopa and dopamine. Investigators and patients were blinded to genotypes data throughout the study. When adjusted for the L-dopa dose, the AUCΔUPDRS was significantly lower in DDC(CC/CT) patients (n = 14) than in DDC(TT) patients (n = 19) and significantly lower in DDC(-/- or AGAG/-) patients (n = 8) than in DDC(AGAG/AGAG) patients (n = 25). There were no significant intergroup differences in plasma pharmacokinetic parameters for L-dopa and dopamine. The rs921451 and rs3837091 polymorphisms of the DDC gene promoter influence the motor response to L-dopa but do not significantly change peripheral pharmacokinetic parameters for L-dopa and dopamine. Our results suggest that DDC may be a genetic modifier of the l-dopa response in Parkinson's disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evidence for adaptive cortical changes in swallowing in Parkinson's disease.

PubMed

Suntrup, Sonja; Teismann, Inga; Bejer, Joke; Suttrup, Inga; Winkels, Martin; Mehler, David; Pantev, Christo; Dziewas, Rainer; Warnecke, Tobias

2013-03-01

Dysphagia is a relevant symptom in Parkinson's disease, whose pathophysiology is poorly understood. It is mainly attributed to degeneration of brainstem nuclei. However, alterations in the cortical contribution to deglutition control in the course of Parkinson's disease have not been investigated. Here, we sought to determine the patterns of cortical swallowing processing in patients with Parkinson's disease with and without dysphagia. Swallowing function in patients was objectively assessed with fiberoptic endoscopic evaluation. Swallow-related cortical activation was measured using whole-head magnetoencephalography in 10 dysphagic and 10 non-dysphagic patients with Parkinson's disease and a healthy control group during self-paced swallowing. Data were analysed applying synthetic aperture magnetometry, and group analyses were done using a permutation test. Compared with healthy subjects, a strong decrease of cortical swallowing activation was found in all patients. It was most prominent in participants with manifest dysphagia. Non-dysphagic patients with Parkinson's disease showed a pronounced shift of peak activation towards lateral parts of the premotor, motor and inferolateral parietal cortex with reduced activation of the supplementary motor area. This pattern was not found in dysphagic patients with Parkinson's disease. We conclude that in Parkinson's disease, not only brainstem and basal ganglia circuits, but also cortical areas modulate swallowing function in a clinically relevant way. Our results point towards adaptive cerebral changes in swallowing to compensate for deficient motor pathways. Recruitment of better preserved parallel motor loops driven by sensory afferent input seems to maintain swallowing function until progressing neurodegeneration exceeds beyond the means of this adaptive strategy, resulting in manifestation of dysphagia.

[A core deficit in Parkinson disease?].

PubMed

Benítez-Burraco, A; Herrera, E; Cuetos, F

2016-05-01

Parkinson disease is a neurodegenerative condition involving motor, cognitive, and linguistic deficits. It is important to know why all these different deficits co-occur in the affected people. This paper aims to clarify whether these comorbid deficits result from the selective impairment of a computational primitive, namely, a context-sensitive computational ability according to Chomsky's Hierarchy (a well-established research tool in comparative neuroscience). A total of 15 medicated subjects with Parkinson disease and 15 controls were selected. They were matched in age and education. A battery of tasks was designed to test 3 different domains (motor capacities, cognition, and language) and 2 different computational abilities (context-free and context-sensitive operations). Significant differences between groups were observed only regarding the linguistic task involving context-sensitive computations (correferences). The observed deficits in our patients with Parkinson disease cannot be explained in terms of the selective impairment of one only unspecific, low-level computational process. At the same time, differences between patients and controls are expected to be greater if the former are not medicated. Moreover, we should pursue in the search of (this kind of) computational primitives than can be selectively impaired in people with Parkinson disease, because they may help to achieve an earlier diagnosis of this condition. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Impact of specialist palliative care on coping with Parkinson's disease: patients and carers.

PubMed

Badger, Nathan J; Frizelle, Dorothy; Adams, Debi; Johnson, Miriam J

2018-06-01

UK guidelines recommend palliative care access for people with Parkinson's disease; however, this remains sporadic, and it is unknown whether specialist palliative care helps patients and carers cope with this distressing condition. This study aimed to explore whether, and how, access to specialist palliative care services affected patients' and carers' coping with Parkinson's disease. Semistructured interviews were conducted, audio-recorded and verbatim transcribed. Data were analysed using interpretative phenomenological analysis. Participants were patients with advanced idiopathic Parkinson's disease (n=3), and carers of people with Parkinson's disease (n=5, however, one diagnosis was reviewed) receiving care from an integrated specialist palliative care and Parkinson's disease service in North East England. Access to specialist palliative care helped participants cope with some aspects of advanced Parkinson's disease. Three superordinate themes were developed:' managing uncertainty', 'impacts on the self' and 'specialist palliative care maintaining a positive outlook'. Specialist palliative care helped patients and carers cope with advanced Parkinson's disease. Specialist palliative care is a complex intervention that acknowledges the complex and holistic nature of Parkinson's disease, enabling health in some domains despite continued presence of pathology. These exploratory findings support the utility of this approach for people living with Parkinson's disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Parkinson's disease in literature, cinema and television].

PubMed

Collado-Vázquez, Susana; Cano-de-la-Cuerda, Roberto; Carrillo, Jesús M

2014-02-01

INTRODUCTION. Since James Parkinson published what can be considered the first treaty on the disease that bears his name in 1817, the scientific literature on this pathology has not ceased to grow. But the illness has also been represented in literature, the cinema and on television, where the symptoms, treatment and socio-familial context of the disease have often been examined very closely. AIM. To address the cases in which Parkinson's disease appears in literature, cinema and television, as well as to reflect on the image of the condition presented in those contexts. DEVELOPMENT. We reviewed some of the most important works in the literature dealing with Parkinson's disease from any period of history and many of them were found to offer very faithful portrayals of the disease. Likewise, we also reviewed major films and TV series that sometimes offer the general public a close look at the vision and the impact of the disease on patients or their relatives. CONCLUSIONS. Literature, cinema and television have helped provide a realistic view of both Parkinson's disease and the related healthcare professionals, and there are many examples that portray the actual experiences of the patients themselves, while also highlighting the importance of healthcare and socio-familial care.

Rasagiline in the pharmacotherapy of Parkinson's disease--a review.

PubMed

Rascol, Olivier

2005-10-01

Despite the current efficacious symptomatic approaches, the search is on for new therapies for Parkinson's disease that can control the cardinal symptoms of the disease (tremor, rigidity and bradykinesia), control/prevent motor complications induced by long-term levodopa, act on non-motor disease symptoms (dementia, dysautonomia, pain, insomnia, falls) and halt disease progression. Rasagiline is a monoamine oxidase-B inhibitor that has demonstrated efficacy against the cardinal symptoms of Parkinson's disease when used as monotherapy in early Parkinson's disease, and as an adjunct to levodopa in advanced disease stages. It reduces the duration and severity of poor symptom response episodes in fluctuating patients. Preliminary results allow discussion of putative effects of rasagiline on some non-motor signs and disease progression. This article outlines the evidence surrounding the efficacy and safety of rasagiline, and discusses its potential to address some of the currently unmet needs of Parkinson's disease therapy.

Lumbar Spine Surgery in Patients with Parkinson Disease.

PubMed

Schroeder, Joshua E; Hughes, Alexander; Sama, Andrew; Weinstein, Joseph; Kaplan, Leon; Cammisa, Frank P; Girardi, Federico P

2015-10-21

Parkinson disease is the second most common neurodegenerative condition. The literature on patients with Parkinson disease and spine surgery is limited, but increased complications have been reported. All patients with Parkinson disease undergoing lumbar spine surgery between 2002 and 2012 were identified. Patients' charts, radiographs, and outcome questionnaires were reviewed. Parkinson disease severity was assessed with use of the modified Hoehn and Yahr staging scale. Complications and subsequent surgeries were analyzed. Risk for reoperation was assessed. Ninety-six patients underwent lumbar spine surgery. The mean patient age was 63.0 years. The mean follow-up duration was 30.1 months. The Parkinson disease severity stage was <2 in thirteen patients, 2 in thirty patients, 2.5 in twenty-three patients, and ≥3 in thirty patients. The primary indication for surgery was spinal stenosis in seventy-two patients, spondylolisthesis in seventeen patients, and coronal and/or sagittal deformity in seven patients. There were nineteen early complications, including postoperative infections requiring surgical irrigation and debridement and long-term antibiotics in ten patients. The visual analog scale for back pain improved from 7.4 cm preoperatively to 1.8 cm postoperatively (p < 0.001). The visual analog scale for lower-limb pain improved from 7.7 cm preoperatively to 2.3 cm postoperatively (p < 0.001). The Oswestry Disability Index score dropped from 54.1 points to 17.7 points at the time of the latest follow-up (p < 0.001). The Short Form-12 Physical Component Summary score improved from 26.6 points preoperatively to 30.5 points postoperatively (p < 0.05). Twenty patients required revision surgery. Risks for further surgery included a Parkinson disease severity stage of ≥3 (p < 0.05), a history of diabetes mellitus, treatment for osteoporosis, and a combined anterior and posterior approach. Despite a higher rate of complications than in the general population, the

PGC-1a Therapy for Parkinson Neurodegeneration

DTIC Science & Technology

2015-06-01

for Parkinson Neurodegeneration 5a. CONTRACT NUMBER W81XWH-14-1-0123 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Howard Federoff...AWARD NUMBER: W81XWH-14-1-0123 TITLE: PGC-1a Therapy for Parkinson Neurodegeneration PRINCIPAL INVESTIGATOR: Dr. Howard Federoff...Unlimited The views, opinions and/or findings contained in this report are those of the author( s ) and should not be construed as an official Department

Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease.

PubMed

Robak, Laurie A; Jansen, Iris E; van Rooij, Jeroen; Uitterlinden, André G; Kraaij, Robert; Jankovic, Joseph; Heutink, Peter; Shulman, Joshua M

2017-12-01

Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants in other lysosomal storage disorder genes is more broadly associated with Parkinson's disease susceptibility. The sequence kernel association test was used to interrogate variant burden among 54 lysosomal storage disorder genes, leveraging whole exome sequencing data from 1156 Parkinson's disease cases and 1679 control subjects. We discovered a significant burden of rare, likely damaging lysosomal storage disorder gene variants in association with Parkinson's disease risk. The association signal was robust to the exclusion of GBA, and consistent results were obtained in two independent replication cohorts, including 436 cases and 169 controls with whole exome sequencing and an additional 6713 cases and 5964 controls with exome-wide genotyping. In secondary analyses designed to highlight the specific genes driving the aggregate signal, we confirmed associations at the GBA and SMPD1 loci and newly implicate CTSD, SLC17A5, and ASAH1 as candidate Parkinson's disease susceptibility genes. In our discovery cohort, the majority of Parkinson's disease cases (56%) have at least one putative damaging variant in a lysosomal storage disorder gene, and 21% carry multiple alleles. Our results highlight several promising new susceptibility loci and reinforce the importance of lysosomal mechanisms in Parkinson's disease pathogenesis. We suggest that multiple genetic hits may act in combination to degrade lysosomal function, enhancing Parkinson's disease susceptibility. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Magnetic resonance spectroscopic study of parkinsonism related to boxing.

PubMed

Davie, C A; Pirtosek, Z; Barker, G J; Kingsley, D P; Miller, P H; Lees, A J

1995-06-01

Proton magnetic resonance spectroscopy, localised to the lentiform nucleus, was carried out in three ex-professional boxers who developed a parkinsonian syndrome, six patients with idiopathic Parkinson's disease, and six age matched controls. The three ex-boxers all showed a pronounced reduction in the absolute concentration of N-acetylaspartate compared with the patients with idiopathic Parkinson's disease and the control group. This reduction is likely to reflect neuronal loss occurring in the putamen and globus pallidus and supports the hypothesis that the extrapyramidal syndrome that may occur in ex-boxers is a distinct entity from idiopathic Parkinson's disease.

Magnetic resonance spectroscopic study of parkinsonism related to boxing.

PubMed Central

Davie, C A; Pirtosek, Z; Barker, G J; Kingsley, D P; Miller, P H; Lees, A J

1995-01-01

Proton magnetic resonance spectroscopy, localised to the lentiform nucleus, was carried out in three ex-professional boxers who developed a parkinsonian syndrome, six patients with idiopathic Parkinson's disease, and six age matched controls. The three ex-boxers all showed a pronounced reduction in the absolute concentration of N-acetylaspartate compared with the patients with idiopathic Parkinson's disease and the control group. This reduction is likely to reflect neuronal loss occurring in the putamen and globus pallidus and supports the hypothesis that the extrapyramidal syndrome that may occur in ex-boxers is a distinct entity from idiopathic Parkinson's disease. Images PMID:7608666

Effect and Mechanism of Chinese Herbal Medicine on Parkinson's Disease.

PubMed

Zeng, Bai-Yun

2017-01-01

Parkinson's disease is a progressive neurodegenerative disorder. Although both genetic and environmental factors are implicated in the development of Parkinson's disease, the cause of the disease is still unclear. So far conventional treatments to Parkinson's are symptomatic relief and focused mainly on motor symptoms. Chinese herbal medicine has been used to treat many conditions in China, Korea, Japan, and many Southeast Asian countries for 1000 years. During past a few decades, Chinese herbal medicine has gained wider and increasing acceptance within both public and medical profession due to its effectiveness on many conditions in western countries. In this chapter, mechanisms of action of many Chinese herbal compounds/extracts and Chinese herb formulas on the models of Parkinson's were reviewed. Further, reports of effectiveness of Chinese herb formulas on patients with Parkinson's were summarized. It was shown that both Chinese herbal compounds/extracts and herb formulas have either specific target mechanisms of action or multitargets mechanisms of action, as antioxidant, antiinflammatory, and antiapoptosis agents. Clinical studies showed that Chinese herb formulas as an adjunct improved both motor and nonmotor symptoms, and reduced dose of dopaminergic drugs and occurrence of dyskinesia. The evidence from the studies suggests that Chinese herb medicine has potential, acting as neuroprotective to slow down the progression of Parkinson's, and it is able to simultaneously treat both motor and nonmotor symptoms of Parkinson's. More studies are needed to explore the new compounds/extracts derived from Chinese herbs, in particular, their mechanisms of action. It is hopeful that new drugs developed from Chinese herb compounds/extracts and Chinese herb formulas will lead to better and complimentary therapy to PD. © 2017 Elsevier Inc. All rights reserved.

Toxoplasma gondii exposure and Parkinson's disease: a case–control study

PubMed Central

Alvarado-Esquivel, Cosme; Méndez-Hernández, Edna Madai; Salas-Pacheco, José Manuel; Ruano-Calderón, Luis Ángel; Hernández-Tinoco, Jesús; Arias-Carrión, Oscar; Sánchez-Anguiano, Luis Francisco; Castellanos-Juárez, Francisco Xavier; Sandoval-Carrillo, Ada Agustina; Liesenfeld, Oliver; Ramos-Nevárez, Agar

2017-01-01

Objectives To determine the association between Toxoplasma gondii infection and Parkinson's disease and to investigate whether T. gondii seropositivity is associated with the general characteristics of patients with Parkinson's disease. Design Case–control study. Setting Cases and controls were enrolled in Durango City, Mexico. Participants 65 patients with Parkinson's disease and 195 age- and gender-matched control subjects without Parkinson's disease. Primary and secondary outcome measures Serum samples of participants were analysed for anti-T. gondii IgG and IgM antibodies by commercially available enzyme-linked immunoassays. Prevalence of T. gondii DNA was determined in seropositive subjects using PCR. The association between clinical data and infection was examined by bivariate analysis. Results Anti-T. gondii IgG antibodies were found in 6/65 cases (9.2%) and in 21/195 controls (10.8%) (OR 0.84; 95% CI 0.32 to 2.18; p=0.81). The frequency of high (>150 IU/mL) antibody levels was similar among cases and controls (p=0.34). None of the anti-T. gondii IgG positive cases and four of the anti-T. gondii IgG positive controls had anti-T. gondii IgM antibodies (p=0.54). The prevalence of T. gondii DNA was comparable in seropositive cases and controls (16.7% and 25%, respectively; p=1.0). Seroprevalence of T. gondii infection was associated with a young age onset of disease (p=0.03), high Unified Parkinson Disease Rating Scale scores (p=0.04) and depression (p=0.02). Seropositivity to T. gondii infection was lower in patients treated with pramipexole than in patients without this treatment (p=0.01). However, none of the associations remained significant after Bonferroni correction. Conclusions The results do not support an association between T. gondii infection and Parkinson's disease. However, T. gondii infection might have an influence on certain symptoms of Parkinson's disease. Further research to elucidate the role of T. gondii exposure on Parkinson's disease

Prognosis of Parkinson disease: risk of dementia and mortality: the Rotterdam Study.

PubMed

de Lau, Lonneke M L; Schipper, C Maarten A; Hofman, Albert; Koudstaal, Peter J; Breteler, Monique M B

2005-08-01

Most prognostic studies on Parkinson disease have been hospital based or have applied register-based case-finding methods. Potential under-representation of mild cases may have given biased results. To evaluate whether Parkinson disease is associated with an increased risk of dementia and death. Population-based cohort study. Parkinson disease and dementia were assessed through in-person examination at baseline (1990-1993) and 2 follow-up visits (1993-1994 and 1997-1999). Computerized linkage to medical and municipality records provided additional information on disease outcomes and mortality. General population. A total of 6969 participants, including 99 prevalent and 67 incident cases of Parkinson disease. Incident dementia and death. Adjusted hazard ratios were calculated through Cox proportional hazards regression analysis. Patients with Parkinson disease had an increased risk of dementia (hazard ratio, 2.8; 95% confidence interval, 1.8-4.4), which was especially pronounced in participants carrying at least 1 apolipoprotein E gene (APOE) epsilon2 allele (13.5; 4.5-40.6). Parkinson disease was associated with an increased mortality risk (1.8; 1.5-2.3). The association consistently diminished when analyses were sequentially restricted to patients with shorter disease duration and after adjustment for the occurrence of dementia. Especially patients with Parkinson disease who carry an APOE epsilon2 allele have an increased risk of developing dementia. Increased mortality risk in Parkinson disease is dependent on disease duration and is only modest in the absence of dementia.

Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension

PubMed Central

Hussain, I; Brady, C; Swinn, M; Mathias, C; Fowler, C

2001-01-01

OBJECTIVES—To assess the efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy.
METHODS—Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital.
RESULTS—Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after sildenafil, all patients with

Psychosis in parkinsonism: an unorthodox approach

PubMed Central

Onofrj, Marco; Carrozzino, Danilo; D’Amico, Aurelio; Di Giacomo, Roberta; Delli Pizzi, Stefano; Thomas, Astrid; Onofrj, Valeria; Taylor, John-Paul; Bonanni, Laura

2017-01-01

Psychosis in Parkinson’s disease (PD) is currently considered as the occurrence of hallucinations and delusions. The historical meaning of the term psychosis was, however, broader, encompassing a disorganization of both consciousness and personality, including behavior abnormalities, such as impulsive overactivity and catatonia, in complete definitions by the International Classification of Diseases-10 (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Our review is aimed at reminding that complex psychotic symptoms, including impulsive overactivity and somatoform disorders (the last being a recent controversial entity in PD), were carefully described in postencephalitic parkinsonism (PEP), many decades before dopaminergic treatment era, and are now described in other parkinsonisms than PD. Eminent neuropsychiatrists of the past century speculated that studying psychosis in PEP might highlight its mechanisms in other conditions. Yet, functional assessments were unavailable at the time. Therefore, the second part of our article reviews the studies of neural correlates of psychosis in parkinsonisms, by taking into account both theories on the narrative functions of the default mode network (DMN) and hypotheses on DMN modulation. PMID:28553118

Aged monkeys as a partial model for Parkinson's disease.

PubMed

Hurley, P J; Elsworth, J D; Whittaker, M C; Roth, R H; Redmond, D E

2011-09-01

Parkinson's Disease (PD) and the natural aging process share a number of biochemical mechanisms, including reduced function of dopaminergic systems. The present study aims to determine the extent that motor and behavioral changes in aged monkeys resemble parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The behavioral and physiological changes in PD are believed to result largely from selective depletion of dopamine in the nigrostriatal system. In the present study, ten aged female monkeys were compared with three groups: 9 untreated young adult female monkeys, 10 young adult male monkeys and 13 older male monkeys that had been exposed to MPTP. Trained observers, blind as to age and drug condition and without knowledge of the hypotheses, scored the monkeys using the Parkinson's factor score (Parkscore), which has been validated by a high correlation with post mortem striatal dopamine (DA) concentrations. The aged animals had higher scores on the Parkscore compared with the young adults, with most of its component behavioral items showing significance (tremor, Eating Problems, Delayed initiation of movement, and Poverty of Movement). L-Dopa and DA-agonists did not clearly reverse the principal measure of parkinsonism. DA concentrations post mortem were 63% lower in 3 aged monkeys in the ventral putamen compared with 4 young adults, with greater reductions in putamen than in caudate (45%). We conclude that aged monkeys, unexposed to MPTP, show a similar profile of parkinsonism to that seen after the neurotoxin exposure to MPTP in young adult monkeys. The pattern of greater DA depletion in putamen than in caudate in aged monkeys is the same as in human Parkinson's disease and contrasts with the greater depletion in caudate seen after MPTP. Aged monkeys of this species reflect many facets of Parkinson's disease, but like older humans do not improve with standard dopamine replacement pharmacotherapies. Copyright © 2011 Elsevier Inc

Data protection in biomaterial banks for Parkinson's disease research: the model of GEPARD (Gene Bank Parkinson's Disease Germany).

PubMed

Eggert, Karla; Wüllner, Ullrich; Antony, Gisela; Gasser, Thomas; Janetzky, Bernd; Klein, Christine; Schöls, Ludger; Oertel, Wolfgang

2007-04-15

Parkinson's disease (PD) is the second most common neurodegenerative disease. Although 10 gene loci have been identified to cause a Parkinsonian syndrome, these loci account only for a minority of PD patients. Large, systematic research programs are required to collect, store, and analyze DNA samples and clinical information to support further discovery of additional genetic components of PD or other movement disorders. Such programs facilitate research into the relationship between genotype and phenotype. The German Competence Network on Parkinson's disease (CNP) initiated the Gene Bank Parkinson's Disease Germany (GEPARD), providing an administrative and scientific infrastructure for the storage of DNA and clinical data that are electronically accessible and protective of patient rights. In this article, we offer guidance on how to establish a framework for a clinical genetic data and DNA bank, and describe GEPARD as a model that may be useful to other local, national, and international research groups developing similar programs.

Restless legs syndrome: an early clinical feature of Parkinson disease in men.

PubMed

Wong, Janice C; Li, Yanping; Schwarzschild, Michael A; Ascherio, Alberto; Gao, Xiang

2014-02-01

The association between restless legs syndrome (RLS) and Parkinson disease has been extensively studied, but the temporal relationship between the two remains unclear. We thus conduct the first prospective study to examine the risk of developing Parkinson disease in RLS. Prospective study from 2002-2010. United States. There were 22,999 US male health professionals age 40-75 y enrolled in the Health Professionals Follow-up Study without Parkinson disease, arthritis, or diabetes mellitus at baseline. RLS was assessed in 2002 using a set of standardized questions recommended by the International RLS Study Group. Incident Parkinson disease was identified by biennial questionnaires and then confirmed by review of participants' medical records by a movement disorder specialist. We documented 200 incident Parkinson disease cases during 8 y of follow-up. Compared to men without RLS, men with RLS symptoms who had symptoms greater than 15 times/mo had higher risk of Parkinson disease development (adjusted relative risk = 1.47; 95% confidence interval: 0.59, 3.65; P = 0.41). This was statistically significant only for cases diagnosed within 4 y of follow-up (adjusted relative risk = 2.77; 95% confidence interval: 1.08, 7.11; P = 0.03). Severe restless legs syndrome may be an early feature of Parkinson disease.

Parkinsonism is associated to fronto-caudate disconnectivity and cognition in schizophrenia.

PubMed

Molina, Vicente; Lubeiro, Alba; Blanco, Jorge; Blanco, José A; Rodríguez, Margarita; Rodríguez-Campos, Alicia; de Luis-García, Rodrigo

2018-07-30

The present work studies the possible relation of parkinsonism and fronto-caudate dysconnectivity, as well as its relation to cognition in schizophrenia patients. We assessed parkinsonism using Simpson-Angus scale and prefronto-caudate connectivity using diffusion magnetic resonance in 22 schizophrenia patients (11 first-episodes) and 14 healthy controls. Fractional anisotropy was calculated for the white matter tracts directly linking rostral middle prefrontal (RMPF) and superior medial prefrontal (SMPF) regions with caudate nucleus. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia Scale (BACS). Total parkinsonism scores were negatively related to fractional anisotropy in the right SMPF-caudate tract in patients, which was also found in the first-episode patients alone, but not in controls. Parkinsonism was also inversely associated in patients to performance in social cognition, verbal memory, working memory and performance speed tests. In conclusion, our data support the involvement of fronto-striatal dysconnectivity in parkinsonism in schizophrenia. Copyright © 2018 Elsevier B.V. All rights reserved.

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…

Clear Speech Variants: An Acoustic Study in Parkinson's Disease

ERIC Educational Resources Information Center

Lam, Jennifer; Tjaden, Kris

2016-01-01

Purpose: The authors investigated how different variants of clear speech affect segmental and suprasegmental acoustic measures of speech in speakers with Parkinson's disease and a healthy control group. Method: A total of 14 participants with Parkinson's disease and 14 control participants served as speakers. Each speaker produced 18 different…

Herpes zoster correlates with increased risk of Parkinson's disease in older people

PubMed Central

Lai, Shih-Wei; Lin, Chih-Hsueh; Lin, Hsien-Feng; Lin, Cheng-Li; Lin, Cheng-Chieh; Liao, Kuan-Fu

2017-01-01

Abstract Little is known on the relationship between herpes zoster and Parkinson's disease in older people. This study aimed to explore whether herpes zoster could be associated with Parkinson's disease in older people in Taiwan. We conducted a retrospective cohort study using the claim data of the Taiwan National Health Insurance Program. There were 10,296 subjects aged 65 years and older with newly diagnosed herpes zoster as the herpes zoster group and 39,405 randomly selected subjects aged 65 years and older without a diagnosis of herpes zoster as the nonherpes zoster group from 1998 to 2010. Both groups were followed up until subjects received a diagnosis of Parkinson's disease. This follow-up design would explore whether subjects with herpes zoster were at an increased risk of Parkinson's disease. Relative risks were estimated by adjusted hazard ratio (HR) and 95% confidence interval (CI) using the multivariable Cox proportional hazards regression model. The incidence of Parkinson's disease was higher in the herpes zoster group than that in the nonherpes zoster group (4.86 vs 4.00 per 1000 person-years, 95% CI 1.14, 1.29). After adjustment for confounding factors, the multivariable Cox proportional hazards regression model revealed that the adjusted HR of Parkinson's disease was 1.17 for the herpes zoster group (95% CI 1.10, 1.25), compared with the nonherpes zoster group. Older people with herpes zoster confer a slightly increased hazard of developing Parkinson's disease when compared to those without herpes zoster. We think that herpes zoster correlates with increased risk of Parkinson's disease in older people. When older people with herpes zoster seek help, clinicians should pay more attention to the development of the cardinal symptoms of Parkinson's disease. PMID:28207515

The intrinsic resting state voice network in Parkinson's disease

PubMed Central

New, Anneliese B.; Parkinson, Amy L.; Eickhoff, Claudia R.; Reetz, Kathrin; Hoffstaedter, Felix; Mathys, Christian; Sudmeyer, Martin; Michely, Jochen; Caspers, Julian; Grefkes, Christian; Larson, Charles R.; Ramig, Loraine O.; Fox, Peter T.; Eickhoff, Simon B.

2015-01-01

Abstract Over 90 percent of patients with Parkinson's disease experience speech‐motor impairment, namely, hypokinetic dysarthria characterized by reduced pitch and loudness. Resting‐state functional connectivity analysis of blood oxygen level‐dependent functional magnetic resonance imaging is a useful measure of intrinsic neural functioning. We utilized resting‐state functional connectivity modeling to analyze the intrinsic connectivity in patients with Parkinson's disease within a vocalization network defined by a previous meta‐analysis of speech (Brown et al., 2009). Functional connectivity of this network was assessed in 56 patients with Parkinson's disease and 56 gender‐, age‐, and movement‐matched healthy controls. We also had item 5 and 18 of the UPDRS, and the PDQ‐39 Communication subscale available for correlation with the voice network connectivity strength in patients. The within‐group analyses of connectivity patterns demonstrated a lack of subcortical–cortical connectivity in patients with Parkinson's disease. At the cortical level, we found robust (homotopic) interhemispheric connectivity but only inconsistent evidence for many intrahemispheric connections. When directly contrasted to the control group, we found a significant reduction of connections between the left thalamus and putamen, and cortical motor areas, as well as reduced right superior temporal gyrus connectivity. Furthermore, most symptom measures correlated with right putamen, left cerebellum, left superior temporal gyrus, right premotor, and left Rolandic operculum connectivity in the voice network. The results reflect the importance of (right) subcortical nodes and the superior temporal gyrus in Parkinson's disease, enhancing our understanding of the neurobiological underpinnings of vocalization impairment in Parkinson's disease. Hum Brain Mapp 36:1951–1962, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.. PMID:25627959

Counterfactual cognitive deficit in persons with Parkinson's disease

PubMed Central

McNamara, P; Durso, R; Brown, A; Lynch, A

2003-01-01

Background: Counterfactuals are mental representations of alternatives to past events. Recent research has shown them to be important for other cognitive processes, such as planning, causal reasoning, problem solving, and decision making—all processes independently linked to the frontal lobes. Objective: To test the hypothesis that counterfactual thinking is impaired in some patients with Parkinson's disease and is linked to frontal dysfunction in these patients. Methods. Measures of counterfactual processing and frontal lobe functioning were administered to 24 persons with Parkinson's disease and 15 age matched healthy controls. Results. Patients with Parkinson's disease spontaneously generated significantly fewer counterfactuals than controls despite showing no differences from controls on a semantic fluency test; they also performed at chance levels on a counterfactual inference test, while age matched controls performed above chance levels on this test. Performance on both the counterfactual generation and inference tests correlated significantly with performance on two tests traditionally linked to frontal lobe functioning (Stroop colour–word interference and Tower of London planning tasks) and one test of pragmatic social communication skills. Conclusions: Counterfactual thinking is impaired in Parkinson's disease. This impairment may be related to frontal lobe dysfunction. PMID:12876235

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

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.

Tension-referenced measures of gastrocnemius slack length and stiffness in Parkinson's disease.

PubMed

Tan, Benedict; Double, Kay L; Burne, John; Diong, Joanna

2016-12-01

It is not known how passive muscle length and stiffness contribute to rigidity in Parkinson's disease. The objective of this study was to compare passive gastrocnemius muscle-tendon slack length and stiffness at known tension in Parkinson's disease subjects with ankle rigidity and in able-bodied people. Passive ankle torque-angle curves were obtained from 15 Parkinson's disease subjects with rigidity and 15 control subjects. Torque-angle data were used to derive passive gastrocnemius length-tension data and calculate slack length and stiffness of the gastrocnemius muscle. Between-group comparisons were made with linear models. Gastrocnemius muscle-tendon slack lengths (adjusted between-group difference, 0.01 m; 95% CI, -0.02 to 0.04 m; P = 0.37) and stiffness (adjusted between-group difference, 15.7 m -1 ; 95% CI, -8.5 to 39.9 m -1 ; P = 0.19) were not significantly different between groups. Parkinson's disease subjects with ankle rigidity did not have significantly shorter or stiffer gastrocnemius muscles compared with control subjects. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Learning about Parkinson's Disease

MedlinePlus

... having genetic testing can learn more about their risk for Parkinson's disease and the availability and accuracy of genetic testing for this disease by setting up an appointment with a genetics health professional. Genetic professionals work as members of health ...

Progression marker of Parkinson's disease: a 4-year multi-site imaging study.

PubMed

Burciu, Roxana G; Ofori, Edward; Archer, Derek B; Wu, Samuel S; Pasternak, Ofer; McFarland, Nikolaus R; Okun, Michael S; Vaillancourt, David E

2017-08-01

Progression markers of Parkinson's disease are crucial for successful therapeutic development. Recently, a diffusion magnetic resonance imaging analysis technique using a bitensor model was introduced allowing the estimation of the fractional volume of free water within a voxel, which is expected to increase in neurodegenerative disorders such as Parkinson's disease. Prior work demonstrated that free water in the posterior substantia nigra was elevated in Parkinson's disease compared to controls across single- and multi-site cohorts, and increased over 1 year in Parkinson's disease but not in controls at a single site. Here, the goal was to validate free water in the posterior substantia nigra as a progression marker in Parkinson's disease, and describe the pattern of progression of free water in patients with a 4-year follow-up tested in a multicentre international longitudinal study of de novo Parkinson's disease (http://www.ppmi-info.org/). The analyses examined: (i) 1-year changes in free water in 103 de novo patients with Parkinson's disease and 49 controls; (ii) 2- and 4-year changes in free water in a subset of 46 patients with Parkinson's disease imaged at baseline, 12, 24, and 48 months; (iii) whether 1- and 2-year changes in free water predict 4-year changes in the Hoehn and Yahr scale; and (iv) the relationship between 4-year changes in free water and striatal binding ratio in a subgroup of Parkinson's disease who had undergone both diffusion and dopamine transporter imaging. Results demonstrated that: (i) free water level in the posterior substantia nigra increased over 1 year in de novo Parkinson's disease but not in controls; (ii) free water kept increasing over 4 years in Parkinson's disease; (iii) sex and baseline free water predicted 4-year changes in free water; (iv) free water increases over 1 and 2 years were related to worsening on the Hoehn and Yahr scale over 4 years; and (v) the 4-year increase in free water was associated with the 4-year

[Morphochemical changes in the substantia nigra cellular structures in Parkinson's disease].

PubMed

Salkov, V N; Khudoerkov, R M; Voronkov, D N; Sobolev, V B; Kutukova, K A

to clarify the features of morphochemical changes in the substantia nigra cellular structures in Parkinson's disease. The structural characteristics of the substantia nigra were studied microscopically and quantified using computer morphometric methods at brain autopsies of individuals with Parkinson's disease who had died from intercurrent diseases and those who had no evidence of neurological disorders in their history (a control group). This investigation could clarify the features of morphochemical changes in both the neural network structures and the glial populations of the substantia nigra in Parkinson's disease. The number of neurons containing tyrosine hydroxylase (a marker of dopamine neurons) in the compact part of the substantia nigra (a ventral region) was smaller and the density distribution of Lewy bodies was higher in the patients with Parkinson's disease than in the control group. The accumulation of iron (II) compounds in the cellular elements and neuropile and the increased expression of glial fibrillary acidic protein in Parkinson's disease were more pronounced than those in the controls. Postmortem diagnosis in Parkinson's disease should be based on a full description of a set of neuronal and glial morphochemical and structural changes in the substantia nigra rather than on the identification of cellular markers for the neurodegenerative process.

Molecular chaperones in Parkinson's disease--present and future.

PubMed

Ebrahimi-Fakhari, Darius; Wahlster, Lara; McLean, Pamela J

2011-01-01

Parkinson's disease, like many other neurodegenerative disorders, is characterized by the progressive accumulation of pathogenic protein species and the formation of intracellular inclusion bodies. The cascade by which the small synaptic protein α-synuclein misfolds to form distinctive protein aggregates, termed Lewy bodies and Lewy neurites, has been the subject of intensive research for more than a decade. Genetic and pathological studies in Parkinson's disease patients as well as experimental studies in disease models have clearly established altered protein metabolism as a key element in the pathogenesis of Parkinson's disease. Alterations in protein metabolism include misfolding and aggregation, post-translational modification and dysfunctional degradation of cytotoxic protein species. Protein folding and re-folding are both mediated by a highly conserved network of molecules, called molecular chaperones and co-chaperones. In addition to the regulatory role in protein folding, molecular chaperone function is intimately associated with pathways of protein degradation, such as the ubiquitin-proteasome system and the autophagy-lysosomal pathway, to effectively remove irreversibly misfolded proteins. Because of the central role of molecular chaperones in maintaining protein homeostasis, we herein review our current knowledge on the involvement of molecular chaperones and co-chaperones in Parkinson's disease. We further discuss the capacity of molecular chaperones to prevent or modulate neurodegeneration, an important concept for future neuroprotective strategies and summarize the current progress in preclinical studies in models of Parkinson's disease and other neurodegenerative disorders. Finally we include a discussion on the future potential of using molecular chaperones as a disease modifying therapy.

Toxin Models of Mitochondrial Dysfunction in Parkinson's Disease

PubMed Central

Martinez, Terina N.

2012-01-01

Abstract Significance: Parkinson's disease (PD) is a neurodegenerative disorder characterized, in part, by the progressive and selective loss of dopaminergic neuron cell bodies within the substantia nigra pars compacta (SNpc) and the associated deficiency of the neurotransmitter dopamine (DA) in the striatum, which gives rise to the typical motor symptoms of PD. The mechanisms that contribute to the induction and progressive cell death of dopaminergic neurons in PD are multi-faceted and remain incompletely understood. Data from epidemiological studies in humans and molecular studies in genetic, as well as toxin-induced animal models of parkinsonism, indicate that mitochondrial dysfunction occurs early in the pathogenesis of both familial and idiopathic PD. In this review, we provide an overview of toxin models of mitochondrial dysfunction in experimental Parkinson's disease and discuss mitochondrial mechanisms of neurotoxicity. Recent Advances: A new toxin model using the mitochondrial toxin trichloroethylene was recently described and novel methods, such as intranasal exposure to toxins, have been explored. Additionally, recent research conducted in toxin models of parkinsonism provides an emerging emphasis on extranigral aspects of PD pathology. Critical Issues: Unfortunately, none of the existing animal models of experimental PD completely mimics the etiology, progression, and pathology of human PD. Future Directions: Continued efforts to optimize established animal models of parkinsonism, as well as the development and characterization of new animal models are essential, as there still remains a disconnect in terms of translating mechanistic observations in animal models of experimental PD into bona fide disease-modifying therapeutics for human PD patients. Antioxid. Redox Signal. 16, 920–934. PMID:21554057

Effects of exercise on mobility in people with Parkinson's disease.

PubMed

van der Kolk, Nicolien M; King, Laurie A

2013-09-15

Parkinson's disease is a prevalent neurodegenerative disorder for which only symptomatic treatment exists. Gait and balance disturbance is common in Parkinson's disease and is a major contributor to increased disability and decreased health-related quality of life and survival. Balance and gait deficits in Parkinson's disease are notoriously difficult to treat and are not significantly helped by pharmacological or surgical treatment. The last two decades have seen a dramatic increase in the research and clinical interest in using exercise as a treatment for mobility problems in people with Parkinson's disease. With exciting advances in basic science research suggesting neurochemical and neuroplastic changes after exercise, an increasing number of high-quality studies are documenting particular aspects of mobility improving after exercise. Exercise has the potential to help both motor (gait, balance, strength) and nonmotor (depression, apathy, fatigue, constipation) aspects of Parkinson's disease as well as secondary complications of immobility (cardiovascular, osteoporosis). This perspective article focuses primarily on recent evidence on the effects of exercise in improving mobility while highlighting the importance of targeted exercise intervention for maximizing the benefits of exercise. Suggestions for exercise guidelines, adherence issues, and directions for future research are provided. © 2013 Movement Disorder Society.

How Is Parkinson's Disease Treated?

MedlinePlus

... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Temporal Lobe and Frontal-Subcortical Dissociations in Non-Demented Parkinson's Disease with Verbal Memory Impairment.

PubMed

Tanner, Jared J; Mareci, Thomas H; Okun, Michael S; Bowers, Dawn; Libon, David J; Price, Catherine C

2015-01-01

The current investigation examined verbal memory in idiopathic non-dementia Parkinson's disease and the significance of the left entorhinal cortex and left entorhinal-retrosplenial region connections (via temporal cingulum) on memory impairment in Parkinson's disease. Forty non-demented Parkinson's disease patients and forty non-Parkinson's disease controls completed two verbal memory tests--a wordlist measure (Philadelphia repeatable Verbal Memory Test) and a story measure (Logical Memory). All participants received T1-weighted and diffusion magnetic resonance imaging (3T; Siemens) sequences. Left entorhinal volume and left entorhinal-retrosplenial connectivity (temporal cingulum edge weight) were the primary imaging variables of interest with frontal lobe thickness and subcortical structure volumes as dissociating variables. Individuals with Parkinson's disease showed worse verbal memory, smaller entorhinal volumes, but did not differ in entorhinal-retrosplenial connectivity. For Parkinson's disease entorhinal-retrosplenial edge weight had the strongest associations with verbal memory. A subset of Parkinson's disease patients (23%) had deficits (z-scores < -1.5) across both memory measures. Relative to non-impaired Parkinson's peers, this memory-impaired group had smaller entorhinal volumes. Although entorhinal cortex volume was significantly reduced in Parkinson's disease patients relative to non-Parkinson's peers, only white matter connections associated with the entorhinal cortex were significantly associated with verbal memory performance in our sample. There was also no suggestion of contribution from frontal-subcortical gray or frontal white matter regions. These findings argue for additional investigation into medial temporal lobe gray and white matter connectivity for understanding memory in Parkinson's disease.

[Juvenile Parkinson's disease and recurring prematurity. Case report].

PubMed

Ha, D-E; Legendre, G; Colau, J-C

2007-03-01

The association of Parkinson's disease and pregnancy is very rare. Some thirty cases are found in the literature. We report the case of a pregnancy in a 30-year-old patient with juvenile Parkinson's disease. During this pregnancy treated by levodopa and bromocriptine, no aggravation of the symptoms was been observed. However, the pregnancy was complicated by a premature delivery at 31 weeks of amenorrhoea.

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. Copyright 2003 Movement Disorder Society

Ambulatory ECG and analysis of heart rate variability in Parkinson's disease.

PubMed

Haapaniemi, T H; Pursiainen, V; Korpelainen, J T; Huikuri, H V; Sotaniemi, K A; Myllylä, V V

2001-03-01

Cardiovascular reflex tests have shown both sympathetic and parasympathetic failure in Parkinson's disease. These tests, however, describe the autonomic responses during a restricted time period and have great individual variability, providing a limited view of the autonomic cardiac control mechanisms. Thus, they do not reflect tonic autonomic regulation. The aim was to examine tonic autonomic cardiovascular regulation in untreated patients with Parkinson's disease. 24 Hour ambulatory ECG was recorded in 54 untreated patients with Parkinson's disease and 47 age matched healthy subjects. In addition to the traditional spectral (very low frequency, VLF; low frequency, LF; high frequency, HF) and non-spectral components of heart rate variability, instantaneous beat to beat variability (SD1) and long term continuous variability (SD2) derived from Poincaré plots, and the slope of the power law relation were analysed. All spectral components (p<0.01) and the slope of the power-law relation (p<0.01) were lower in the patients with Parkinson's disease than in the control subjects. The Unified Parkinson's disease rating scale total and motor scores had a negative correlation with VLF and LF power spectrum values and the power law relation slopes. Patients with mild hypokinesia had higher HF values than patients with more severe hypokinesia. Tremor and rigidity were not associated with the HR variability parameters. Parkinson's disease causes dysfunction of the diurnal autonomic cardiovascular regulation as demonstrated by the spectral measures of heart rate variability and the slope of the power law relation. This dysfunction seems to be more profound in patients with more severe Parkinson's disease.

Cardiac autonomic denervation in Parkinson's disease is linked to REM sleep behavior disorder.

PubMed

Postuma, Ronald B; Montplaisir, Jacques; Lanfranchi, Paola; Blais, Hélène; Rompré, Sylvie; Colombo, Roberto; Gagnon, Jean-François

2011-07-01

Recent studies have suggested a close connection between autonomic dysfunction and rapid eye movement sleep behavior disorder, which differs in nature from other early-stage markers of Parkinson's disease. In this study we examined the relationship between rapid eye movement sleep behavior disorder and autonomic dysfunction in Parkinson's disease as measured by cardiac beat-to-beat variability. In 53 patients with Parkinson's disease and 36 controls, electrocardiographic trace from a polysomnogram was assessed for measures of beat-to-beat RR variability including RR-standard deviation and frequency domains (low- and high-frequency components). Results were compared between patients with Parkinson's disease and controls, and between patients with Parkinson's disease with and without rapid eye movement sleep behavior disorder. On numerous cardiac autonomic measures, patients with Parkinson's disease showed clear abnormalities compared with controls. However, these abnormalities were confined only to those patients with associated rapid eye movement sleep behavior; those without were not different than controls. As with other clinical autonomic variables, cardiac autonomic denervation is predominantly associated not with Parkinson's disease itself, but with the presence of rapid eye movement sleep behavior disorder. Copyright © 2011 Movement Disorder Society.

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 was the…

Risk of Falls in Parkinson's Disease: A Cross-Sectional Study of 160 Patients

PubMed Central

Contreras, Ana; Grandas, Francisco

2012-01-01

Falls are a major source of disability in Parkinson's disease. Risk factors for falling in Parkinson's disease remain unclear. To determine the relevant risk factors for falling in Parkinson's disease, we screened 160 consecutive patients with Parkinson's disease for falls and assessed 40 variables. A comparison between fallers and nonfallers was performed using statistical univariate analyses, followed by bivariate and multivariate logistic regression, receiver-operating characteristics analysis, and Kaplan-Meier curves. 38.8% of patients experienced falls since the onset of Parkinson's disease (recurrent in 67%). Tinetti Balance score and Hoehn and Yahr staging were the best independent variables associated with falls. The Tinetti Balance test predicted falls with 71% sensitivity and 79% specificity and Hoehn and Yahr staging with 77% sensitivity and 71% specificity. The risk of falls increased exponentially with age, especially from 70 years onward. Patients aged >70 years at the onset of Parkinson's disease experienced falls significantly earlier than younger patients. PMID:22292126

Treadmill exercise alleviates nigrostriatal dopaminergic loss of neurons and fibers in rotenone-induced Parkinson rats.

PubMed

Shin, Mal-Soon; Kim, Tae-Woon; Lee, Jae-Min; Ji, Eun-Sang; Lim, Baek-Vin

2017-02-01

Parkinson disease is one of the common brain diseases caused by dopaminergic neuronal loss in the substantia nigra and dopaminergic fiber loss in the striatum. In the present study, the effects of treadmill exercise on motor performance, dopaminergic loss of neurons and fibers, and α-synuclein expression in the nigrostriatum were evaluated using rotenone-induced Parkinson rats. For the induction of Parkinson rats, 3-mg/kg rotenone was injected, once a day for 14 consecutive days. Treadmill running was conducted for 30 min once a day during 14 consecutive days. Rota-rod test for motor balance and coordination and immunohistochemistry for tyrosine hydroxylase and α-synuclein in the nigrostriatum were performed. In the present study, motor balance and coordination was disturbed by induction of rotenone-induced Parkinson disease, in contrast, treadmill exercise alleviated motor dysfunction in the rotenone-induced Parkinson rats. Nigrostriatal dopaminergic loss of neurons and fibers was occurred by induction of rotenone-induced Parkinson disease, in contrast, treadmill exercise alleviated nigrostriatal dopaminergic loss of neurons and fibers in the rotenone-induced Parkinson rats. α-Synuclein expression in the nigrostriatum was enhanced by induction of rotenone-induced Parkinson disease, in contrast, treadmill exercise suppressed α-synuclein expression in the rotenone-induced Parkinson rats. Treadmill exercise improved motor function through preservation of nigrostriatal dopaminergic neurons and fibers and suppression of nigrostriatal formation of Lewy bodies in rotenone-induced Parkinson rats.

Toxoplasma gondii exposure and Parkinson's disease: a case-control study.

PubMed

Alvarado-Esquivel, Cosme; Méndez-Hernández, Edna Madai; Salas-Pacheco, José Manuel; Ruano-Calderón, Luis Ángel; Hernández-Tinoco, Jesús; Arias-Carrión, Oscar; Sánchez-Anguiano, Luis Francisco; Castellanos-Juárez, Francisco Xavier; Sandoval-Carrillo, Ada Agustina; Liesenfeld, Oliver; Ramos-Nevárez, Agar

2017-02-13

To determine the association between Toxoplasma gondii infection and Parkinson's disease and to investigate whether T. gondii seropositivity is associated with the general characteristics of patients with Parkinson's disease. Case-control study. Cases and controls were enrolled in Durango City, Mexico. 65 patients with Parkinson's disease and 195 age- and gender-matched control subjects without Parkinson's disease. Serum samples of participants were analysed for anti- T. gondii IgG and IgM antibodies by commercially available enzyme-linked immunoassays. Prevalence of T. gondii DNA was determined in seropositive subjects using PCR. The association between clinical data and infection was examined by bivariate analysis. Anti- T. gondii IgG antibodies were found in 6/65 cases (9.2%) and in 21/195 controls (10.8%) (OR 0.84; 95% CI 0.32 to 2.18; p=0.81). The frequency of high (>150 IU/mL) antibody levels was similar among cases and controls (p=0.34). None of the anti- T. gondii IgG positive cases and four of the anti- T. gondii IgG positive controls had anti- T. gondii IgM antibodies (p=0.54). The prevalence of T. gondii DNA was comparable in seropositive cases and controls (16.7% and 25%, respectively; p=1.0). Seroprevalence of T. gondii infection was associated with a young age onset of disease (p=0.03), high Unified Parkinson Disease Rating Scale scores (p=0.04) and depression (p=0.02). Seropositivity to T. gondii infection was lower in patients treated with pramipexole than in patients without this treatment (p=0.01). However, none of the associations remained significant after Bonferroni correction. The results do not support an association between T. gondii infection and Parkinson's disease. However, T. gondii infection might have an influence on certain symptoms of Parkinson's disease. Further research to elucidate the role of T. gondii exposure on Parkinson's disease is warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not

Dopamine controls Parkinson's tremor by inhibiting the cerebellar thalamus.

PubMed

Dirkx, Michiel F; den Ouden, Hanneke E M; Aarts, Esther; Timmer, Monique H M; Bloem, Bastiaan R; Toni, Ivan; Helmich, Rick C

2017-03-01

Parkinson's resting tremor is related to altered cerebral activity in the basal ganglia and the cerebello-thalamo-cortical circuit. Although Parkinson's disease is characterized by dopamine depletion in the basal ganglia, the dopaminergic basis of resting tremor remains unclear: dopaminergic medication reduces tremor in some patients, but many patients have a dopamine-resistant tremor. Using pharmacological functional magnetic resonance imaging, we test how a dopaminergic intervention influences the cerebral circuit involved in Parkinson's tremor. From a sample of 40 patients with Parkinson's disease, we selected 15 patients with a clearly tremor-dominant phenotype. We compared tremor-related activity and effective connectivity (using combined electromyography-functional magnetic resonance imaging) on two occasions: ON and OFF dopaminergic medication. Building on a recently developed cerebral model of Parkinson's tremor, we tested the effect of dopamine on cerebral activity associated with the onset of tremor episodes (in the basal ganglia) and with tremor amplitude (in the cerebello-thalamo-cortical circuit). Dopaminergic medication reduced clinical resting tremor scores (mean 28%, range -12 to 68%). Furthermore, dopaminergic medication reduced tremor onset-related activity in the globus pallidus and tremor amplitude-related activity in the thalamic ventral intermediate nucleus. Network analyses using dynamic causal modelling showed that dopamine directly increased self-inhibition of the ventral intermediate nucleus, rather than indirectly influencing the cerebello-thalamo-cortical circuit through the basal ganglia. Crucially, the magnitude of thalamic self-inhibition predicted the clinical dopamine response of tremor. Dopamine reduces resting tremor by potentiating inhibitory mechanisms in a cerebellar nucleus of the thalamus (ventral intermediate nucleus). This suggests that altered dopaminergic projections to the cerebello-thalamo-cortical circuit have a role

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

[Nature of speech disorders in Parkinson disease].

PubMed

Pawlukowska, W; Honczarenko, K; Gołąb-Janowska, M

2013-01-01

The aim of the study was to discuss physiology and pathology of speech and review of the literature on speech disorders in Parkinson disease. Additionally, the most effective methods to diagnose the speech disorders in Parkinson disease were also stressed. Afterward, articulatory, respiratory, acoustic and pragmatic factors contributing to the exacerbation of the speech disorders were discussed. Furthermore, the study dealt with the most important types of speech treatment techniques available (pharmacological and behavioral) and a significance of Lee Silverman Voice Treatment was highlighted.

Palliative care for Parkinson's disease: Patient and carer's perspectives explored through qualitative interview.

PubMed

Fox, Siobhan; Cashell, Alison; Kernohan, W George; Lynch, Marie; McGlade, Ciara; O'Brien, Tony; O'Sullivan, Sean S; Foley, Mary J; Timmons, Suzanne

2017-07-01

Palliative care is recommended for non-malignant illnesses, including Parkinson's disease. However, past research with healthcare workers highlights unmet palliative needs in this population and referral rates to Specialist Palliative Care are low. Some healthcare workers perceive a 'fear' in their patients about introducing palliative care. However, less is known about the views of people with Parkinson's disease and their carers about palliative care. (1) To explore the palliative care and related issues most affecting people with Parkinson's disease and their families and (2) to examine perceptions about/understanding of palliative care. This was a qualitative study; semi-structured interviews were conducted, transcribed and analysed using thematic analysis. A total of 31 people participated, both people with Parkinson's disease ( n = 19) and carers ( n = 12), across three Movement Disorder Clinics in the Republic of Ireland. People with Parkinson's disease and their carers were unfamiliar with the term palliative care. When informed of the role of palliative care, most felt that they would benefit from this input. People with Parkinson's disease and carers experienced a high illness burden and wanted extra support. Crises requiring Specialist Palliative Care involvement may occur at diagnosis and later, with advancing illness. Participants wanted more information about palliative care and especially further supports to address their psychosocial needs. A holistic palliative care approach could address the complex physical and psychosocial symptoms experienced by people with Parkinson's disease and their carers, and people with Parkinson's disease and their carers are open to palliative care. Further research needs to explore how palliative care can be introduced into the routine care for people with Parkinson's disease.

Seasonal temperature is associated with Parkinson's disease prescriptions: an ecological study

NASA Astrophysics Data System (ADS)

Rowell, David; Nghiem, Son; Ramagopalan, Sreeram; Meier, Ute-Christiane

2017-12-01

The aim of this study is to test what effect the weather may have on medications prescribed to treat Parkinson's disease. Twenty-three years of monthly time, series data was sourced from the Pharmaceutical Benefits Scheme (PBS) and the Bureau of Meteorology (BOM). Data were available for eight states and territories and their corresponding capital cities. The dependent variable was the aggregate levodopa equivalent dose (LED) for 51 Parkinson's medications identified on the PBS. Two explanatory variables of interest, temperature and solar exposure, were identified in the BOM data set. Linear and cosinor models were estimated with fixed and random effects, respectively. The prescribed LED was 4.2% greater in January and 4.5% lower in July. Statistical analysis showed that temperature was associated with the prescription of Parkinson medications. Our results suggest seasonality exists in Parkinson's disease symptoms and this may be related to temperature. Further work is needed to confirm these findings and understand the underlying mechanisms as a better understanding of the causes of any seasonal variation in Parkinson's disease may help clinicians and patients manage the disease more effectively.

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

PubMed

Houston, Sara; McGill, Ashley

2013-06-01

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.

Rasch analysis of the carers quality of life questionnaire for parkinsonism.

PubMed

Pillas, Marios; Selai, Caroline; Schrag, Anette

2017-03-01

To assess the psychometric properties of the Carers Quality of Life Questionnaire for Parkinsonism using a Rasch modeling approach and determine the optimal cut-off score. We performed a Rasch analysis of the survey answers of 430 carers of patients with atypical parkinsonism. All of the scale items demonstrated acceptable goodness of fit to the Rasch model. The scale was unidimensional and no notable differential item functioning was detected in the items regarding age and disease type. Rating categories were functioning adequately in all scale items. The scale had high reliability (.95) and construct validity and a high degree of precision, distinguishing between 5 distinct groups of carers with different levels of quality of life. A cut-off score of 62 was found to have the optimal screening accuracy based on Hospital Anxiety and Depression Scale subscores. The results suggest that the Carers Quality of Life Questionnaire for Parkinsonism is a useful scale to assess carers' quality of life and allows analyses requiring interval scaling of variables. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Nucleus basalis of Meynert degeneration precedes and predicts cognitive impairment in Parkinson's disease.

PubMed

Schulz, Jonathan; Pagano, Gennaro; Fernández Bonfante, Juan Alberto; Wilson, Heather; Politis, Marios

2018-05-01

Currently, no reliable predictors of cognitive impairment in Parkinson's disease exist. We hypothesized that microstructural changes at grey matter T1-weighted MRI and diffusion tensor imaging in the cholinergic system nuclei and associated limbic pathways underlie cognitive impairment in Parkinson's disease. We performed a cross-sectional comparison between patients with Parkinson's disease with and without cognitive impairment. We also performed a longitudinal 36-month follow-up study of cognitively intact Parkinson's disease patients, comparing patients who remained cognitively intact to those who developed cognitive impairment. Patients with Parkinson's disease with cognitive impairment showed lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert, compared to patients with Parkinson's disease without cognitive impairment. These results were confirmed both with region of interest and voxel-based analyses, and after partial volume correction. Lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert was predictive for developing cognitive impairment in cognitively intact patients with Parkinson's disease, independent of other clinical and non-clinical markers of the disease. Structural and microstructural alterations in entorhinal cortex, amygdala, hippocampus, insula, and thalamus were not predictive for developing cognitive impairment in Parkinson's disease. Our findings provide evidence that degeneration of the nucleus basalis of Meynert precedes and predicts the onset of cognitive impairment, and might be used in a clinical setting as a reliable biomarker to stratify patients at higher risk of cognitive decline.

On the role of endogenous neurotoxins and neuroprotection in Parkinson's disease.

PubMed

Segura-Aguilar, Juan

2017-06-01

For 50 years ago was introduced L-3,4-dihydroxyphenylalanine (L-dopa) in Parkinson's disease treatment and during this significant advances has been done but what trigger the degeneration of the nigrostriatal system remain unknown. There is a general agreement in the scientific community that mitochondrial dysfunction, protein degradation dysfunction, alpha-synuclein aggregation to neurotoxic oligomers, neuroinflammation, oxidative and endoplasmic reticulum stress are involved in the loss of dopaminergic neurons containing neuromelanin in Parkinson's disease. The question is what triggers these mechanisms. The age of normal onset in idiopathic Parkinson's disease suggests that environmental factors such as metals, pollutants or genetic mutations cannot be involved because these factors are related to early onset of Parkinsonism. Therefore, we have to search for endogenous neurotoxins and neuroprotection in order to understand what trigger the loss of dopaminergic neurons. One important feature of Parkinson's disease is the rate of the degenerative process before the motor symptoms are evident and during the disease progression. The extremely slow rate of Parkinson's disease suggests that the neurotoxins and the neuroprotection have to be related to dopamine metabolism. Possible candidates for endogenous neurotoxins are alpha-synuclein neurotoxic oligomers, 4-dihydroxyphenylacetaldehyde and ortho-quinones formed during dopamine oxidation to neuromelanin. Vesicular monoamine transporter-2, DT-diaphorase and glutathione transferase M2-2 seems to be the most important neuroprotective mechanism to prevent neurotoxic mechanism during dopamine oxidation.

Familial Hemiplegic Migraine Type 1 Associated with Parkinsonism: A Case Report

PubMed Central

Bruun, Marie; Hjermind, Lena Elisabeth; Thomsen, Carsten; Danielsen, Else; Thomsen, Lise Lykke; Pinborg, Lars Hageman; Khabbazbavani, Nastaran; Nielsen, Joergen Erik

2015-01-01

Familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) are allelic disorders caused by mutations in the CACNA1A gene on chromosome 19p13. It is well described that FHM1 can present with cerebellar signs, but parkinsonism has not previously been reported in FHM1 or EA2 even though parkinsonism has been described in SCA6. We report a 63-year-old woman with FHM1 caused by an R583Q mutation in the CACNA1A gene, clinically presenting with migraine and permanent cerebellar ataxia. Since the age of 60 years, the patient also developed parkinsonism with rigidity, bradykinesia and a resting tremor. An MRI showed a normal substantia nigra, but a bilateral loss of substance in the basal ganglia, which is in contrast to the typically normal MRI in idiopathic Parkinson's disease. Dopamine transporter (DAT) imaging with single-photon emission computed tomography demonstrated a decreased DAT-binding potential in the putamen. We wish to draw attention to FHM1 associated with parkinsonism; however, whether the reported case is a consequence of FHM1 being allelic to SCA6, unknown modifiers to the specific R583Q CACNA1A mutation or idiopathic Parkinson's disease remains unanswered. PMID:25969684

Parkinson's disease: the spectrum of disabilities.

PubMed Central

Pentland, B; Barnes, M P; Findley, L J; Oxtoby, M; Pearce, V R; Quinn, N P; Scott, S

1992-01-01

The needs of people with Parkinson's disease (PD) go beyond the purely medical domain and often require collaborative management. A Panel Discussion at the "Hither neurology" Symposium included neurologists, a speech therapist, a geriatrician and a sociologist. Their discussion highlighted certain aspects of the disability and disadvantage associated with PD. The starting point was a video recording, "Parkinson's Disease: the personal view", in which the contributors were patients and carers. Topics covered included counselling at the time of diagnosis; subsequent access to clinics and to neurological advice; access to therapy; support in the community; fluctuating disability associated with "on-off" phenomena; driving; and sexual problems. PMID:1564503

Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson's Disease

ClinicalTrials.gov

2018-02-27

Idiopathic Parkinson's Disease; Parkinson's Disease; Basal Ganglia Disease; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Nervous System Diseases; Neurodegenerative Diseases; Parkinsonian Disorders

Prying into the Prion Hypothesis for Parkinson's Disease.

PubMed

Brundin, Patrik; Melki, Ronald

2017-10-11

In Parkinson's disease, intracellular α-synuclein inclusions form in neurons. We suggest that prion-like behavior of α-synuclein is a key component in Parkinson's disease pathogenesis. Although multiple molecular changes are involved in the triggering of the disease process, we propose that neuron-to-neuron transfer is a crucial event that is essential for Lewy pathology to spread from one brain region to another. In this review, we describe key findings in human postmortem brains, cultured cells, and animal models of disease that support the idea that α-synuclein can act as a prion. We consider potential triggers of the α-synuclein misfolding and why the aggregates escape cellular degradation under disease conditions. We also discuss whether different strains of α-synuclein fibrils can underlie differences in cellular and regional distribution of aggregates in different synucleinopathies. Our conclusion is that α-synuclein probably acts as a prion in human diseases, and a deeper understanding of this step in the pathogenesis of Parkinson's disease can facilitate the development of disease-modifying therapies in the future. Dual Perspectives Companion Paper: Parkinson's Disease Is Not Simply a Prion Disorder, by D. James Surmeier, José A. Obeso, and Glenda M. Halliday. Copyright © 2017 the authors 0270-6474/17/379808-11$15.00/0.

Parkin in Parkinson's Disease and Cancer: a Double-Edged Sword.

PubMed

Wahabi, Khushnuma; Perwez, Ahmad; Rizvi, Moshahid A

2018-01-18

Parkin for more than a decade has been portrayed as a neuroprotector gene is now increasingly emerging as a multifaceted gene that can exert entirely opposite effects i.e., both cell proliferation and apoptosis. Parkinson's disease, a neurological disease, progresses due to excess in cell death, while, in case of cancer, cell death normally fails to occur. Parkin, an E3 ubiquitin ligase, was first identified as a gene implicated in autosomal recessive juvenile Parkinsonism, but several evidences indicate that Parkin is a tumor suppressor gene, involved in a variety of cancers. It is hard to imagine that two entirely different classes of disease, like cancer and Parkinson's disease, can converge at a critical point attributable to a single gene, Parkin. This mysterious and hidden connection may prove a boon in disguise and has raised hopes that studying the biology of one disease may help to identify novel targets of therapy for the other. In this Parkinson's disease-cancer story, if the detail of Parkin pathway is unraveled and gaps in the storyline are properly filled up, we may end getting an entirely new therapeutic option. This review mainly highlights the recent literature which suggests how Parkin gene regulates the various hallmarks of both the Parkinson's disease and cancer.

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.

[Emotional facial expression recognition impairment in Parkinson disease].

PubMed

Lachenal-Chevallet, Karine; Bediou, Benoit; Bouvard, Martine; Thobois, Stéphane; Broussolle, Emmanuel; Vighetto, Alain; Krolak-Salmon, Pierre

2006-03-01

some behavioral disturbances observed in Parkinson's disease (PD) could be related to impaired recognition of various social messages particularly emotional facial expressions. facial expression recognition was assessed using morphed faces (five emotions: happiness, fear, anger, disgust, neutral), and compared to gender recognition and general cognitive assessment in 12 patients with Parkinson's disease and 14 controls subjects. facial expression recognition was impaired among patients, whereas gender recognitions, visuo-perceptive capacities and total efficiency were preserved. Post hoc analyses disclosed a deficit for fear and disgust recognition compared to control subjects. the impairment of emotional facial expression recognition in PD appears independent of other cognitive deficits. This impairment may be related to the dopaminergic depletion in basal ganglia and limbic brain regions. They could take a part in psycho-behavioral disorders and particularly in communication disorders observed in Parkinson's disease patients.

Impulse control disorders in advanced Parkinson's disease with dyskinesia: The ALTHEA study.

PubMed

Biundo, Roberta; Weis, Luca; Abbruzzese, Giovanni; Calandra-Buonaura, Giovanna; Cortelli, Pietro; Jori, Maria Cristina; Lopiano, Leonardo; Marconi, Roberto; Matinella, Angela; Morgante, Francesca; Nicoletti, Alessandra; Tamburini, Tiziano; Tinazzi, Michele; Zappia, Mario; Vorovenci, Ruxandra Julia; Antonini, Angelo

2017-11-01

Impulse control disorders and dyskinesia are common and disabling complications of dopaminergic treatment in Parkinson's disease. They may coexist and are possibly related. The objectives of this study were to assess the frequency and severity of impulse control disorders in Parkinson's disease patients with dyskinesia. The ALTHEA study enrolled 251 Parkinson's disease patients with various degrees of dyskinesia severity from 11 movement disorders centers in Italy. Each patient underwent a comprehensive assessment including Unified Dyskinesia Rating Scale and the Questionnaire for Impulsive Compulsive Disorders in Parkinson Disease-Rating Scale. There was an overall 55% frequency of impulse control disorder and related behaviors (36% were clinically significant). The positive patients were younger at disease diagnosis and onset and had higher Unified Dyskinesia Rating Scale historical and total score (P = 0.001 and P = 0.02, respectively, vs negative). There was an increased frequency of clinically significant impulse control disorders in patients with severe dyskinesia (P = 0.013), a positive correlation between the questionnaire total score and dopamine agonist dose (P = 0.018), and a trend with levodopa dose. More than half of Parkinson's disease patients with dyskinesia have impulse control disorders and related behaviors, which are frequently clinically significant. Dopaminergic therapy total dose is associated with their severity. Clinicians should carefully assess patients with maladaptive behaviors and dyskinesia because they do not properly evaluate their motor and nonmotor status. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Greater risk of parkinsonism associated with non-N370S GBA1 mutations

PubMed Central

Giraldo, P.; Capablo, J. L.; Alfonso, P.; Irun, P.; Garcia-Rodriguez, B.; Pocovi, M.; Pastores, G. M.

2014-01-01

Mutations in β-glucosidase (GBA1) are the most common genetic risk factor for Parkinson disease (PD). There is evidence to suggest that PD risk is greater (1) in GBA1 heterozygotes with non-N370S GBA1 mutations compared to N370S mutations and (2) in GD type 1 (GD1) patients compared to GBA1 heterozygotes. This study aimed to determine the comparative risk of parkin-sonism in individuals who are affected or carriers of Gaucher disease (GD) and to ascertain the influence of different GBA1 mutations on risk/clinical expression. We conducted a secondary analysis of cross-sectional data assessing the prevalence of parkinsonism in a population of GD1 patients and their heterozygote and non-carrier family members. Two logistic regression models, both employing a family-specific random effect, were used to assess (1) the association between GBA1 mutation (N370S or non-N370S) and parkinsonism among GBA1 heterozygotes and (2) the association between GBA1 genotype and parkinsonism. Parkinsonism was present in 8.6 % of GD1 (7/81), 8.7 % of GBA1 heterozygotes (18/207), and 2.2 % of non-carriers (1/45). For those greater than 60 years old, parkinsonism was present in 38.5 % (5/13) of GD1 (5/13), 15.3 % of GBA1 heterozygotes (13/85), and 7.1 % of non-carriers (1/14). Among GBA1 heterozygotes, non-N370S mutations were associated with a significantly increased risk of parkinsonism compared to N370S (OR=22.5; p=0.035; 95%CI: 1.24, 411). In this population, each additional GBA1 mutation was associated with a non-significant two-fold increased risk of parkinsonism. GBA1 heterozygotes with non-N370S mutations associated with Gaucher disease have an increased risk of parkinsonism compared to those with N370S mutations. PMID:22968580

The efficacy and feasibility of aquatic physiotherapy for people with Parkinson's disease: a systematic review.

PubMed

Terrens, Aan Fleur; Soh, Sze-Ee; Morgan, Prue Elizabeth

2017-08-09

To critically evaluate the literature regarding the efficacy and feasibility of aquatic physiotherapy in people with Parkinson's disease. Relevant studies were identified through searches in nine health-related databases. Two independent reviewers assessed study quality using either the PEDro scale or a customised tool for safety and feasibility. Database searches yielded 88 articles, of which 10 met the inclusion criteria. Studies varied greatly in methodology, quality, interventions and outcome measures. Study quality was generally low in items reporting on safety precautions, adverse events, attrition, and adherence. Results suggest that aquatic physiotherapy may have a positive effect on motor symptoms, quality of life and balance. Aquatic physiotherapy may improve aspects of motor performance, quality of life and balance in people with Parkinson's disease, however, it remains unclear whether it is a safe and feasible treatment modality. The development of standardised outcome measures for people with Parkinson's disease (unified Parkinson's disease rating scale and Parkinson's disease questionnaire-39) would aid study comparability and validate study outcomes. As safety criteria was grossly underreported, guidelines for mandatory reporting of safety criteria are essential to make conclusions regarding the feasibility of aquatic physiotherapy for people with Parkinson's disease. Implications for Rehabilitation Aquatic physiotherapy may be a beneficial treatment modality for people with Parkinson's disease. A minimum data set that includes the unified Parkinson's disease rating scale and Parkinson's disease questionnaire 39 is required to aid future meta-analysis and to allow more definitive conclusions to be made regarding aquatic physiotherapy for people with Parkinson's disease. People with Parkinson's disease are a vulnerable population, where safety within an aquatic physiotherapy program needs to be well documented and addressed.

Database for Parkinson Disease Mutations and Rare Variants

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W81XWH-14-1-0097 TITLE: “ Database for Parkinson Disease Mutations and Rare Variants” PRINCIPAL INVESTIGATOR: JEFFERY M. VANCE...TO THE ABOVE ADDRESS. 1. REPORT DATE September 2016 2. REPORT TYPE FINAL 3. DATES COVERED 1 Jul 2014 – 30 Jun 2016 4. TITLE AND SUBTITLE Database ...For Parkinson Disease (PD) specifically, the variant databases currently available are incomplete, don’t assess impact and/or are not equipped to

Diet and Nutrition (Parkinson's Disease)

MedlinePlus

... Area Resources & Support PD Library Legal, Financial, & Insurance Matters Blog For Caregivers Living with Parkinson's While living ... into your diet. These include brightly colored and dark fruits and vegetables. Balance the food you eat ...

The Roles of PINK1, Parkin and Mitochondrial Fidelity in Parkinson's Disease

PubMed Central

Pickrell, Alicia M.; Youle, Richard J.

2015-01-01

Understanding the function of genes mutated in hereditary forms of Parkinson's disease yields insight into disease etiology and reveals new pathways in cell biology. Although mutations or variants in many genes increase the susceptibility to Parkinson's disease, only a handful of monogenic causes of Parkinsonism have been identified. Biochemical and genetic studies reveal that the products of two genes that are mutated in autosomal recessive Parkinsonism, PINK1 and Parkin, normally work together in the same pathway to govern mitochondrial quality control, bolstering previous evidence that mitochondrial damage is involved in Parkinson's disease. PINK1 accumulates on the outer membrane of damaged mitochondria, activates Parkin's E3 ubiquitin ligase activity and recruits Parkin to the dysfunctional mitochondrion. Then, Parkin ubiquitinates outer mitochondrial membrane proteins to trigger selective autophagy. This review covers the normal functions that PINK1 and Parkin play within cells, their molecular mechanisms of action, and the pathophysiological consequences of their loss. PMID:25611507

Dopamine-dependent neurodegeneration in Drosophila models of familial and sporadic Parkinson's disease.

PubMed

Bayersdorfer, Florian; Voigt, Aaron; Schneuwly, Stephan; Botella, José A

2010-10-01

Parkinson's disease has been found to be caused by both, genetic and environmental factors. Despite the diversity of causes involved, a convergent pathogenic mechanism might underlie the special vulnerability of dopaminergic neurons in different forms of Parkinsonism. In recent years, a number of reports have proposed dopamine as a common player responsible in the loss of dopaminergic neurons independent of its etiology. Using RNAi lines we were able to generate flies with drastically reduced dopamine levels in the dopaminergic neurons. Combining these flies with a chemically induced Parkinson model (rotenone) and a familial form of Parkinson (mutant alpha-synuclein) we were able to show a strong reduction of neurotoxicity and a protection of the dopaminergic neurons when cellular dopamine levels were reduced. These results show that dopamine homeostasis plays a central role for the susceptibility of dopaminergic neurons to environmental and genetic factors in in vivo models of Parkinson disease. (c) 2010 Elsevier Inc. All rights reserved.

Semantic trouble sources and their repair in conversations affected by Parkinson's disease

PubMed Central

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 problems become manifest in everyday conversations or how conversation partners handle such problems. Aims To describe the pragmatic problems related to the use of words that occur in everyday conversational interaction in dyads including an individual with Parkinson's disease, and to explore how interactants in conversation handle the problems to re-establish mutual understanding. Methods & Procedures Twelve video-recorded everyday conversations involving three couples where one of the individuals had Parkinson's disease were included in the study. All instances of other-initiated repair following a contribution from the people with Parkinson's disease were analysed. Those instances involving a trouble source relating to the use of words were analysed with a qualitative interaction analysis based on the principles of conversation analysis. Outcomes & Results In 70% of the instances of other-initiated repair the trouble source could be related to the semantic content produced by the individual with Parkinson's disease. The problematic contributions were typically characterized by more or less explicit symptoms of word search or use of atypical wording. The conversation partners completed the repair work collaboratively, but typically the non-impaired individual made a rephrasing or provided a suggestion for what the intended meaning had been. Conclusions & Implications In clinical work with people with Parkinson's disease and their conversation partners it is important to establish what type of trouble sources occur in conversations in a specific dyad. It may often be necessary to look beyond intelligibility and into aspects of pragmatics

Cognitive states influence dopamine-driven aberrant learning in Parkinson's disease.

PubMed

Cavanagh, James F; Mueller, Andrea A; Brown, Darin R; Janowich, Jacqueline R; Story-Remer, Jacqueline H; Wegele, Ashley; Richardson, Sarah Pirio

2017-05-01

Individual differences in dopaminergic tone underlie tendencies to learn from reward versus punishment. These effects are well documented in Parkinson's patients, who vacillate between low and high tonic dopaminergic states as a function of medication. Yet very few studies have investigated the influence of higher-level cognitive states known to affect downstream dopaminergic learning in Parkinson's patients. A dopamine-dependent cognitive influence over learning would provide a candidate mechanism for declining cognitive integrity and motivation in Parkinson's patients. In this report we tested the influence of two high-level cognitive states (cost of conflict and value of volition) that have recently been shown to cause predictable learning biases in healthy young adults as a function of dopamine receptor subtype and dopaminergic challenge. It was hypothesized that Parkinson's patients OFF medication would have an enhanced cost of conflict and a decreased value of volition, and that these effects would be remediated or reversed ON medication. Participants included N = 28 Parkinson's disease patients who were each tested ON and OFF dopaminergic medication and 28 age- and sex-matched controls. The expected cost of conflict effect was observed in Parkinson's patients OFF versus ON medication, but only in those that were more recently diagnosed (<5 years). We found an unexpected effect in the value of volition task: medication compromised the ability to learn from difficult a-volitional (instructed) choices. This novel finding was also enhanced in recently diagnosed patients. The difference in learning biases ON versus OFF medication between these two tasks was strongly correlated, bolstering the idea that they tapped into a common underlying imbalance in dopaminergic tone that is particularly variable in earlier stage Parkinsonism. The finding that these decision biases are specific to earlier but not later stage disease may offer a chance for future studies to

Pramipexole in the treatment of Parkinson's disease: new developments.

PubMed

Möller, J Carsten; Oertel, Wolfgang H

2005-09-01

The nonergot dopamine agonist pramipexole is an efficient and safe drug for the treatment of Parkinson's disease. Clinicians may favor pramipexole over other dopamine agonists because of its suggested higher tolerability with respect to peripheral dopaminergic side effects. Importantly, nonergot dopamine agonists such as pramipexole may not cause restrictive valvular heart disease and may therefore represent the first choice in patients with valvular lesions under treatment with ergot dopamine agonists. However, particular caution has to be exercised in younger Parkinson's disease patients with a shorter disease duration regarding the occurrence of sudden onset of sleep. In light of cost-effectiveness and quality-of-life issues, its final significance for the initial treatment of patients with early Parkinson's disease remains to be determined.

"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…

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…

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

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 ...

Inverse Association of Parkinson Disease With Systemic Lupus Erythematosus: A Nationwide Population-based Study.

PubMed

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

2015-11-01

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.

Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson's disease.

PubMed

Melzer, Tracy R; Watts, Richard; MacAskill, Michael R; Pearson, John F; Rüeger, Sina; Pitcher, Toni L; Livingston, Leslie; Graham, Charlotte; Keenan, Ross; Shankaranarayanan, Ajit; Alsop, David C; Dalrymple-Alford, John C; Anderson, Tim J

2011-03-01

There is a need for objective imaging markers of Parkinson's disease status and progression. Positron emission tomography and single photon emission computed tomography studies have suggested patterns of abnormal cerebral perfusion in Parkinson's disease as potential functional biomarkers. This study aimed to identify an arterial spin labelling magnetic resonance-derived perfusion network as an accessible, non-invasive alternative. We used pseudo-continuous arterial spin labelling to measure cerebral grey matter perfusion in 61 subjects with Parkinson's disease with a range of motor and cognitive impairment, including patients with dementia and 29 age- and sex-matched controls. Principal component analysis was used to derive a Parkinson's disease-related perfusion network via logistic regression. Region of interest analysis of absolute perfusion values revealed that the Parkinson's disease pattern was characterized by decreased perfusion in posterior parieto-occipital cortex, precuneus and cuneus, and middle frontal gyri compared with healthy controls. Perfusion was preserved in globus pallidus, putamen, anterior cingulate and post- and pre-central gyri. Both motor and cognitive statuses were significant factors related to network score. A network approach, supported by arterial spin labelling-derived absolute perfusion values may provide a readily accessible neuroimaging method to characterize and track progression of both motor and cognitive status in Parkinson's disease.

Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells.

PubMed

McNeill, Alisdair; Magalhaes, Joana; Shen, Chengguo; Chau, Kai-Yin; Hughes, Derralyn; Mehta, Atul; Foltynie, Tom; Cooper, J Mark; Abramov, Andrey Y; Gegg, Matthew; Schapira, Anthony H V

2014-05-01

Gaucher disease is caused by mutations in the glucocerebrosidase gene, which encodes the lysosomal hydrolase glucosylceramidase. Patients with Gaucher disease and heterozygous glucocerebrosidase mutation carriers are at increased risk of developing Parkinson's disease. Indeed, glucocerebrosidase mutations are the most frequent risk factor for Parkinson's disease in the general population. Therefore there is an urgent need to understand the mechanisms by which glucocerebrosidase mutations predispose to neurodegeneration to facilitate development of novel treatments. To study this we generated fibroblast lines from skin biopsies of five patients with Gaucher disease and six heterozygous glucocerebrosidase mutation carriers with and without Parkinson's disease. Glucosylceramidase protein and enzyme activity levels were assayed. Oxidative stress was assayed by single cell imaging of dihydroethidium. Glucosylceramidase enzyme activity was significantly reduced in fibroblasts from patients with Gaucher disease (median 5% of controls, P = 0.0001) and heterozygous mutation carriers with (median 59% of controls, P = 0.001) and without (56% of controls, P = 0.001) Parkinson's disease compared with controls. Glucosylceramidase protein levels, assessed by western blot, were significantly reduced in fibroblasts from Gaucher disease (median glucosylceramidase levels 42% of control, P < 0.001) and heterozygous mutation carriers with (median 59% of control, P < 0.001) and without (median 68% of control, P < 0.001) Parkinson's disease. Single cell imaging of dihydroethidium demonstrated increased production of cytosolic reactive oxygen species in fibroblasts from patients with Gaucher disease (dihydroethidium oxidation rate increased by a median of 62% compared to controls, P < 0.001) and heterozygous mutation carriers with (dihydroethidium oxidation rate increased by a median of 68% compared with controls, P < 0.001) and without (dihydroethidium oxidation rate increased by a

Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

PubMed

Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D

2018-01-01

The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

Platelet monoamine oxidase B and plasma β-phenylethylamine in Parkinson's disease

PubMed Central

Zhou, G; Miura, Y; Shoji, H; Yamada, S; Matsuishi, T

2001-01-01

OBJECTIVE—To evaluate the correlation between changes in platelet monoamine oxidase type B (MAO-B) activity and plasma β-phenylethylamine (PEA) concentrations in patients with Parkinson's disease and controls.
METHODS—Platelet MAO-B activity and plasma PEA were measured with gas chromatography-mass spectrometry (GC-MS) in patients with Parkinson's disease treated with levodopa (12 men and 12 women) or selegiline (three men and three women), and physically healthy subjects as a control group (10 men and 10women).
RESULTS—Platelet MAO-B activity was significantly higher in the Parkinson's disease group (mean 542 (SD 318) pmol/107 platelets/30 min) than in the control group (mean 349 (SD 307) pmol/107 platelets/30 min) (p<0.05). By contrast, the plasma PEA concentrations in patients with Parkinson's disease were significantly lower than in the control group (mean 532 (SD 243) pg/ml; 931 (SD 560) pg/ml) (p<0.01). The plasma PEA concentrations in patients with Parkinson's disease treated with selegiline were prominently higher than in patients with no selegiline treatment (p<0.001). There was a significantly negative correlation between platelet MAO-B activity and plasma PEA concentrations in patients (n=24, r=−0.466, p<0.001).
CONCLUSIONS—The increase in platelet MAO-B activity and decrease in plasma PEA concentrations in patients with Parkinson's disease may be involved in the pathophysiological processes of the disease, and these changes are reversed by treatment with selegiline.

 PMID:11160474

The Prevalence of Parkinson Disease Among Patients With Hepatitis C Infection.

PubMed

Golabi, Pegah; Otgonsuren, Munkhzul; Sayiner, Mehmet; Arsalla, Aimal; Gogoll, Trevor; Younossi, Zobair M

HCV has been suspected to potentially cause degenerations in the central nervous system. Parkinson's disease is the second most common neurodegenerative disorder. Our aim was to assess the prevalence of Parkinson's disease among patients with HCV infection. For this study, we used Medicare database from 2005-2010. Medicare database contains information on enrollment, coverage, diagnosis recorded with International Classification of Disease, Ninth Revision (ICD-9). From combined inpatient and outpatient files, Parkinson's disease was identified as the first diagnosis by ICD-9 code 332.0. Other study variables were; age, gender, race (White and No White), and Medicare eligibility status. Simple distribution comparison by HCV status examined with t-test for numerical variables and ?2 test for categorical variables in the main analytical cohort as well as in the propensity score matched cohort. A total of 1,236,734 patients (median age 76 years, 41% male, and 85% White) was identified among over 47 million claims. Of these, 6040 patients (0.5%) were infected with HCV. Overall, 0.8% (N = 49) of the HCV group and 1.3% (N = 16,004) of the Non-HCV group had Parkinson's disease (P < 0.001). When the study groups matched for age, gender and race, the prevalence of Parkinson's disease was similar between HCV and Non-HCV groups (P > 0.05). This study revealed that, among Medicare population, HCV was not associated with Parkinson disease.

Parkinson's disease as a system-level disorder.

PubMed

Caligiore, Daniele; Helmich, Rick C; Hallett, Mark; Moustafa, Ahmed A; Timmermann, Lars; Toni, Ivan; Baldassarre, Gianluca

2016-01-01

Traditionally, the basal ganglia have been considered the main brain region implicated in Parkinson's disease. This single area perspective gives a restricted clinical picture and limits therapeutic approaches because it ignores the influence of altered interactions between the basal ganglia and other cerebral components on Parkinsonian symptoms. In particular, the basal ganglia work closely in concert with cortex and cerebellum to support motor and cognitive functions. This article proposes a theoretical framework for understanding Parkinson's disease as caused by the dysfunction of the entire basal ganglia-cortex-cerebellum system rather than by the basal ganglia in isolation. In particular, building on recent evidence, we propose that the three key symptoms of tremor, freezing, and impairments in action sequencing may be explained by considering partially overlapping neural circuits including basal ganglia, cortical and cerebellar areas. Studying the involvement of this system in Parkinson's disease is a crucial step for devising innovative therapeutic approaches targeting it rather than only the basal ganglia. Possible future therapies based on this different view of the disease are discussed.

Recent advances in Parkinson's disease therapy: use of monoamine oxidase inhibitors.

PubMed

Henchcliffe, Claire; Schumacher, H Christian; Burgut, F Tuna

2005-11-01

Monoamine oxidase inhibitors inhibit dopamine metabolism and are therefore effective in treating Parkinson's disease, a condition associated with progressive striatal dopamine deficiency secondary to degeneration of dopaminergic neurons in the substantia nigra. Selegiline is currently the most widely used monoamine oxidase-B inhibitor for Parkinson's disease, but has a low and variable bioavailability, and is metabolized to L-methamphetamine and L-amphetamine that carry a risk for potential neurotoxicity. There are two new approaches that circumvent these potential disadvantages. First, selegiline orally disintegrating tablets provide a novel delivery form of selegiline, avoiding first pass metabolism by rapid absorption through the oral mucosa, thus leading to significantly lower plasma concentrations of L-metamphetamine and L-amphetamine. Selegiline orally disintegrating tablets prove to be clinically effective and safe in patients with moderately advanced Parkinson's disease. Second, rasagiline is a new monoamine oxidase inhibitor, without known neurotoxic metabolites. In large clinical trials, rasagiline proves effective as monotherapy in early Parkinson's disease, as well as adjunctive therapy to levodopa in advanced disease. Clinical data suggest, in addition, a disease-modifying effect of rasagiline that may correlate with neuroprotective activity of monoamine oxidase-B inhibitors in animal models of Parkinson's disease.

Developments in impulse control behaviours of Parkinson's disease.

PubMed

Zurowski, Mateusz; O'Brien, Jonathan Darcy

2015-08-01

Impulse control behaviours (ICBs) are a frequent comorbidity for patients with Parkinson's disease. They consist of impulse control disorders, dopamine dysregulation syndrome, and punding. The field continues to evolve in the understanding of impulsivity and assessment of risk factors in the development of these behaviours and their appropriate management in patients with Parkinson's disease. Impulsivity is a multifaceted concept that is surprisingly common in untreated patients with Parkinson's disease. The incidence of ICBs increases with demographic, clinical, and biochemical risk factors. Treatments rely on reduction of dopamine agonists with exception of cognitive behavioural therapy and possibly repetitive transcranial magnetic stimulation. Reduction of dopamine agonist dose is the mainstay of treatment of ICBs. Other forms of dopaminergic treatment such as deep brain stimulation or jejunal infusion are alternative treatments but may be complicated by dopamine agonist withdrawal syndrome. Other therapies show promise but data are insufficient to suggest their regular use.

Different Functional and Microstructural Changes Depending on Duration of Mild Cognitive Impairment in Parkinson Disease.

PubMed

Shin, N-Y; Shin, Y S; Lee, P H; Yoon, U; Han, S; Kim, D J; Lee, S-K

2016-05-01

The higher cortical burden of Lewy body and Alzheimer disease-type pathology has been reported to be associated with a faster onset of cognitive impairment of Parkinson disease. So far, there has been a few studies only about the changes of gray matter volume depending on duration of cognitive impairment in Parkinson disease. Therefore, our aim was to evaluate the different patterns of structural and functional changes in Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. Fifty-nine patients with Parkinson disease with mild cognitive impairment were classified into 2 groups on the basis of shorter (<1 year, n = 16) and longer (≥1 year, n = 43) durations of parkinsonism before mild cognitive impairment. Fifteen drug-naïve patients with de novo Parkinson disease with intact cognition were included for comparison. Cortical thickness, Tract-Based Spatial Statistics, and seed-based resting-state functional connectivity analyses were performed. Age, sex, years of education, age at onset of parkinsonism, and levodopa-equivalent dose were included as covariates. The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased fractional anisotropy and increased mean and radial diffusivity values in the frontal areas compared with the group with longer duration of parkinsonism before mild cognitive impairment (corrected P < .05). The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity in the default mode network area when the left or right posterior cingulate was used as a seed, and in the dorsolateral prefrontal areas when the left or right caudate was used as a seed (corrected P < .05). The group with longer duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity mainly in the medial prefrontal cortex when the left or right

Spotlight on rotigotine transdermal patch in Parkinson's disease.

PubMed

Sanford, Mark; Scott, Lesley J

2011-12-01

Rotigotine transdermal patch (Neupro(®)) [referred to here as rotigotine] is a non-ergolinic dopamine agonist that is available in the EU as monotherapy for the treatment of early Parkinson's disease and as combination therapy with levodopa throughout the course of the disease. Daily application of the rotigotine patch provided predictable release and absorption of rotigotine, with steady-state rotigotine concentrations reached within 1-2 days. In early Parkinson's disease, compared with placebo, rotigotine monotherapy produced significantly greater improvements in the Unified Parkinson's Disease Rating Scale summed motor and activities of daily living (ADL) scores (primary endpoint), as well as significantly higher response rates. In advanced Parkinson's disease, rotigotine in combination with levodopa reduced 'off' time (primary endpoint) and improved motor functioning and ADL significantly more than levodopa plus placebo. In patients with inadequate early morning motor control despite antiparkinsonian treatment, rotigotine improved morning motor functioning and reduced sleep disturbances, night-time motor symptoms, depressive symptoms, pain and functioning, and quality of life to a significantly greater extent than placebo. The efficacy of rotigotine relative to other treatments requires further evaluation, as there were inconsistent results in noninferiority analyses that compared rotigotine to other dopamine agonists. Rotigotine was generally well tolerated across the trials, with the most common treatment-emergent adverse events being application-site reactions, gastrointestinal disturbances, somnolence and headache. No unexpected adverse effects were observed in extension studies of up to 6 years. Thus, rotigotine offers a novel approach to the treatment of Parkinson's disease and, given its ease of administration, efficacy in reducing disabling motor and non-motor symptoms, and acceptable tolerability profile, it has the potential to be an attractive

Pedunculopontine network dysfunction in Parkinson's disease with postural control and sleep disorders.

PubMed

Gallea, Cecile; Ewenczyk, Claire; Degos, Bertrand; Welter, Marie-Laure; Grabli, David; Leu-Semenescu, Smaranda; Valabregue, Romain; Berroir, Pierre; Yahia-Cherif, Lydia; Bertasi, Eric; Fernandez-Vidal, Sara; Bardinet, Eric; Roze, Emmanuel; Benali, Habib; Poupon, Cyril; François, Chantal; Arnulf, Isabelle; Lehéricy, Stéphane; Vidailhet, Marie

2017-05-01

The objective of this study was to investigate pedunculopontine nucleus network dysfunctions that mediate impaired postural control and sleep disorder in Parkinson's disease. We examined (1) Parkinson's disease patients with impaired postural control and rapid eye movement sleep behavior disorder (further abbreviated as sleep disorder), (2) Parkinson's disease patients with sleep disorder only, (3) Parkinson's disease patients with neither impaired postural control nor sleep disorder, and (4) healthy volunteers. We assessed postural control with clinical scores and biomechanical recordings during gait initiation. Participants had video polysomnography, daytime sleepiness self-evaluation, and resting-state functional MRIs. Patients with impaired postural control and sleep disorder had longer duration of anticipatory postural adjustments during gait initiation and decreased functional connectivity between the pedunculopontine nucleus and the supplementary motor area in the locomotor network that correlated negatively with the duration of anticipatory postural adjustments. Both groups of patients with sleep disorder had decreased functional connectivity between the pedunculopontine nucleus and the anterior cingulate cortex in the arousal network that correlated with daytime sleepiness. The degree of dysfunction in the arousal network was related to the degree of connectivity in the locomotor network in all patients with sleep disorder, but not in patients without sleep disorder or healthy volunteers. These results shed light on the functional neuroanatomy of pedunculopontine nucleus networks supporting the clinical manifestation and the interdependence between sleep and postural control impairments in Parkinson's disease. © 2016 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Impulse control disorders and levodopa-induced dyskinesias in Parkinson's disease: an update.

PubMed

Voon, Valerie; Napier, T Celeste; Frank, Michael J; Sgambato-Faure, Veronique; Grace, Anthony A; Rodriguez-Oroz, Maria; Obeso, Jose; Bezard, Erwan; Fernagut, Pierre-Olivier

2017-03-01

Dopaminergic medications used in the treatment of patients with Parkinson's disease are associated with motor and non-motor behavioural side-effects, such as dyskinesias and impulse control disorders also known as behavioural addictions. Levodopa-induced dyskinesias occur in up to 80% of patients with Parkinson's after a few years of chronic treatment. Impulse control disorders, including gambling disorder, binge eating disorder, compulsive sexual behaviour, and compulsive shopping occur in about 17% of patients with Parkinson's disease on dopamine agonists. These behaviours reflect the interactions of the dopaminergic medications with the individual's susceptibility, and the underlying neurobiology of Parkinson's disease. Parkinsonian rodent models show enhanced reinforcing effects of chronic dopaminergic medication, and a potential role for individual susceptibility. In patients with Parkinson's disease and impulse control disorders, impairments are observed across subtypes of decisional impulsivity, possibly reflecting uncertainty and the relative balance of rewards and losses. Impairments appear to be more specific to decisional than motor impulsivity, which might reflect differences in ventral and dorsal striatal engagement. Emerging evidence suggests impulse control disorder subtypes have dissociable correlates, which indicate that individual susceptibility predisposes towards the expression of different behavioural subtypes and neurobiological substrates. Therapeutic interventions to treat patients with Parkinson's disease and impulse control disorders have shown efficacy in randomised controlled trials. Large-scale studies are warranted to identify individual risk factors and novel therapeutic targets for these diseases. Mechanisms underlying impulse control disorders and dyskinesias could provide crucial insights into other behavioural symptoms in Parkinson's disease and addictions in the general population. Copyright © 2017 Elsevier Ltd. All rights

Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies.

PubMed

Wile, Daryl J; Agarwal, Pankaj A; Schulzer, Michael; Mak, Edwin; Dinelle, Katherine; Shahinfard, Elham; Vafai, Nasim; Hasegawa, Kazuko; Zhang, Jing; McKenzie, Jessamyn; Neilson, Nicole; Strongosky, Audrey; Uitti, Ryan J; Guttman, Mark; Zabetian, Cyrus P; Ding, Yu-Shin; Adam, Mike; Aasly, Jan; Wszolek, Zbigniew K; Farrer, Matthew; Sossi, Vesna; Stoessl, A Jon

2017-05-01

People with Parkinson's disease can show premotor neurochemical changes in the dopaminergic and non-dopaminergic systems. Using PET, we assessed whether dopaminergic and serotonin transporter changes are similar in LRRK2 mutation carriers with Parkinson's disease and individuals with sporadic Parkinson's disease, and whether LRRK2 mutation carriers without motor symptoms show PET changes. We did two cross-sectional PET studies at the Pacific Parkinson's Research Centre in Vancouver, BC, Canada. We included LRRK2 mutation carriers with or without manifest Parkinson's disease, people with sporadic Parkinson's disease, and age-matched healthy controls, all aged 18 years or older. People with Parkinson's disease were diagnosed by a neurologist with movement disorder training, in accordance with the UK Parkinson's Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger sequencing. In the first study, LRRK2 mutation carriers with or without manifest Parkinson's disease who were referred for investigation between July, 1999, and January, 2012, were scanned with PET tracers for the membrane dopamine transporter, and dopamine synthesis and storage ( 18 F-6-fluoro-L-dopa; 18 F-FDOPA). We compared findings with those in people with sporadic Parkinson's disease and age-matched healthy controls. In the second study, distinct groups of LRRK2 mutation carriers, individuals with sporadic Parkinson's disease, and age-matched healthy controls seen from November, 2012, to May, 2016, were studied with tracers for the serotonin transporter and vesicular monoamine transporter 2 (VMAT2). Striatal dopamine transporter binding, VMAT2 binding, 18 F-FDOPA uptake, and serotonin transporter binding in multiple brain regions were compared by ANCOVA, adjusted for age. Between January, 1997, and January, 2012, we obtained data for our first study from 40 LRRK2 mutation carriers, 63 individuals with sporadic Parkinson's disease, and 35 healthy controls. We

French consensus procedure for assessing cognitive function in Parkinson's disease.

PubMed

Dujardin, K; Auzou, N; Lhommée, E; Czernecki, V; Dubois, B; Fradet, A; Maltete, D; Meyer, M; Pineau, F; Schmitt, E; Sellal, F; Tison, F; Vidal, T; Azulay, J-P; Welter, M-L; Corvol, J-C; Durif, F; Rascol, O

2016-11-01

One of the objectives of the French expert centers for Parkinson's disease (NS-Park) network was to determine a consensus procedure for assessing cognitive function in patients with Parkinson's. This article presents this procedure and briefly describes the selected tests. A group of 13 experts used the Delphi method for consensus building to define the overall structure and components of the assessment procedure. For inclusion in the battery, tests had to be validated in the French language, require little motor participation, have normative data and be recognized by the international community. Experimental tasks and tests requiring specific devices were excluded. Two possibilities were identified, depending on whether an abbreviated or comprehensive assessment of cognitive function was necessary. For an abbreviated assessment, the experts recommended the Montreal Cognitive Assessment (MoCA) as a screening test for cognitive impairment or dementia. For a comprehensive neuropsychological assessment, the experts recommended assessing global efficiency plus the five main cognitive domains (attention and working memory, executive function, episodic memory, visuospatial function and language) that may be impaired in Parkinson's disease, using two tests for each domain. A common procedure for assessing cognitive function is now available across the French network dedicated to Parkinson's disease, and is recommended for both research and clinical practice. It will also help to promote standardization of the neuropsychological assessment of Parkinson's disease. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Acupuncture as Adjuvant Therapy for Sleep Disorders in Parkinson's Disease.

PubMed

Aroxa, Fábio Henrique de Amorim; Gondim, Ihana Thaís Guerra de Oliveira; Santos, Elba Lúcia Wanderley; Coriolano, Maria das Graças Wanderley de Sales; Asano, Amdore Guescel C; Asano, Nadja Maria Jorge

2017-01-01

There are few studies which attest the efficacy of acupuncture on treatment of sleep disturbs in Parkinson disease. The aimed of this randomized clinical trial was to evaluate the effects of acupuncture on sleep disturbs of 22 patients with diagnosis of idiopathic Parkinson disease (Hoehn-Yahr 1 to 3) who have assistance on the Pro-Parkinson Program of Clinical Hospital at Federal University of Pernambuco in Brazil. All participants were evaluated by Parkinson Disease Sleep Scale (PDSS) before and after 8 weeks. The experimental group was submitted to 8 sections (once a week) which had duration of 30 minutes. The control group had no intervention. The intervention was executed using the acupuncture points LR3 (Taichong), SP6 (Sanyinjiao), LI4 (Hegu), TE5 (Wai-Guan), HT7 (Shenmen), PC6 (Neiguan), LI11 (Quchi), GB20 (Fengchi). Paired analyses were obtained by Wilcoxon test and independent analyses were made according to Mann-Whitney test. This study presented a potential therapeutic benefit of acupuncture on sleep disturbs of Parkinson's disease patients. This study showed a possible therapeutic benefit through acupuncture in sleep disorders in patients with PD. However, we propose new studies related to the effects of acupuncture on the clinical symptoms and evolution of the disease. Copyright © 2017 Medical Association of Pharmacopuncture Institute. Published by Elsevier B.V. All rights reserved.

Quantitative Motor Performance and Sleep Benefit in Parkinson Disease.

PubMed

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

2015-10-01

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. 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. 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. 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. © 2015 Associated Professional Sleep Societies, LLC.

[Cognitive and neuropsychiatric disorders in Parkinson's disease].

PubMed

Rodríguez-Constenla, I; Cabo-López, I; Bellas-Lamas, P; Cebrián, E

2010-02-08

In Parkinson's disease there are patients with isolated and multiple cognitive impairment, and their cognitive performance ranges from normal to an advanced degree of dementia. Most patients present an executive deficit, either in isolation or combined with other cognitive disorders, which is considered to be the most characteristic aspect of the disease, and 30-40% of those affected will end up with a clinically-defined dementia. The presence of a mild cognitive disorder in patients with Parkinson means that the risk of dementia appearing at some time during the development of the disease is high. The dementia associated with Parkinson's disease is specifically related with neuropsychiatric signs and symptoms, which may have three possible explanations: disorders affecting the mesolimbic pathways, diffuse limbic and cortical compromise, or associated Alzheimer-type phenomenology. Psychotic episodes tend to present more often in patients with dopaminergic treatment and the clinical spectrum of Parkinson-related psychosis covers visual illusions, visual-audio-olfactory hallucinations, delirium and severe paranoid hallucinatory psychosis. All the antiparkinsonian drugs can give rise to hallucinations and psychosis, but the dopamine agonists are the ones with the greatest capacity to do so. In managing these problems, it is crucial for prevention as well as diagnosis and treatment to be carried out as soon as they are detected. Doses of antiparkinsonian drugs must be reduced, although this is not usually enough, and so it will be necessary to associate atypical antipsychotics, which act mainly on 5-HT receptors and, in most cases, do not produce D2 blockage.

Nonmotor symptoms in a malaysian Parkinson's disease population.

PubMed

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 (r s : 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.

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'.

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.

Experiences of fear of falling in persons with Parkinson's disease - a qualitative study.

PubMed

Jonasson, Stina B; Nilsson, Maria H; Lexell, Jan; Carlsson, Gunilla

2018-02-06

Fear of falling is common among persons with Parkinson's disease and is negatively associated with quality of life. However a lack of in-depth understanding of fear of falling as a phenomenon persists. This qualitative study aimed to explore the experiences of fear of falling in persons with Parkinson's disease. Individual interviews were performed with twelve persons with Parkinson's disease (median age 70 years, median Parkinson duration 9 years, 50% women). The interviews were semi-structured and followed a study-specific interview guide. The transcribed interviews were analyzed using qualitative content analysis. Fear of falling was experienced as a disturbing factor in everyday life. It generated a feeling of vulnerability and made daily activities and everyday environments seem potentially hazardous. Persons also missed performing previous activities. The fear of falling was a varying experience, fueled by an awareness of falls and near falls, Parkinson-related symptoms and disabilities, and by others in their environment. The persons adopted different strategies to handle their fear of falling. Activities were adapted, avoided, performed with help, or carried out despite their fear of falling. The experiences of fear of falling were complex, multifaceted and varied over time and in relation to different activities and environments. This indicates that interventions targeting fear of falling need to be individually tailored for persons with Parkinson's disease and should focus on several aspects, such as Parkinson-related symptoms and disabilities, activities and environmental factors. This study provides new information that increases the understanding of fear of falling, which has implications for researchers as well as clinicians working with persons with Parkinson's disease and fear of falling.

A unique retinal epitheliopathy is associated with amyotrophic lateral sclerosis/Parkinsonism-Dementia complex of Guam.

PubMed

Steele, John C; Wresch, Robert; Hanlon, Samuel D; Keystone, Jay; Ben-Shlomo, Yoav

2015-08-01

The aim of this work was to examine whether a linear retinal pigment epitheliopathy is associated with the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam. A total of 918 Guamanian Chamorros, with and without amyotrophic lateral sclerosis/parkinsonism-dementia complex, were examined cross-sectionally for linear retinal pigment epitheliopathy (LRPE). Overall, 239 Guamanians, who were neurologically asymptomatic, were followed for up to 20 years to determine the risk of developing amyotrophic lateral sclerosis/parkinsonism-dementia complex. The epitheliopathy was present in 59.7% (117 of 196) patients with amyotrophic lateral sclerosis/parkinsonism-dementia complex, but in only 24.7% (178 of 722) of subjects who were neurologically asymptomatic (age- and sex-adjusted risk difference: 35.0%; 95% confidence interval [CI]: 27.5-42.6; p < 0.0001). Prospectively, 15 of 50 cases with epitheliopathy developed amyotrophic lateral sclerosis/parkinsonism-dementia complex, compared to 4 of 189 cases without epitheliopathy (age- and sex-adjusted hazard ratio: 13.1; 95% CI: 4.0-43.1; P < 0.0001). Amyotrophic lateral sclerosis/parkinsonism-dementia complex is associated with an LRPE and predicts future neurological disease. Identifying the cause of this retinopathy could provide an understanding about the pathogenesis of amyotrophic lateral sclerosis/parkinsonism-dementia complex and related diseases. © 2015 International Parkinson and Movement Disorder Society.

Pathological synchronization in Parkinson's disease: networks, models and treatments.

PubMed

Hammond, Constance; Bergman, Hagai; Brown, Peter

2007-07-01

Parkinson's disease is a common and disabling disorder of movement owing to dopaminergic denervation of the striatum. However, it is still unclear how this denervation perverts normal functioning to cause slowing of voluntary movements. Recent work using tissue slice preparations, animal models and in humans with Parkinson's disease has demonstrated abnormally synchronized oscillatory activity at multiple levels of the basal ganglia-cortical loop. This excessive synchronization correlates with motor deficit, and its suppression by dopaminergic therapies, ablative surgery or deep-brain stimulation might provide the basic mechanism whereby diverse therapeutic strategies ameliorate motor impairment in patients with Parkinson's disease. This review is part of the INMED/TINS special issue, Physiogenic and pathogenic oscillations: the beauty and the beast, based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).

Factors Associated With Ambulatory Activity in De Novo Parkinson Disease.

PubMed

Christiansen, Cory; Moore, Charity; Schenkman, Margaret; Kluger, Benzi; Kohrt, Wendy; Delitto, Anthony; Berman, Brian; Hall, Deborah; Josbeno, Deborah; Poon, Cynthia; Robichaud, Julie; Wellington, Toby; Jain, Samay; Comella, Cynthia; Corcos, Daniel; Melanson, Ed

2017-04-01

Objective ambulatory activity during daily living has not been characterized for people with Parkinson disease prior to initiation of dopaminergic medication. Our goal was to characterize ambulatory activity based on average daily step count and examine determinants of step count in nonexercising people with de novo Parkinson disease. We analyzed baseline data from a randomized controlled trial, which excluded people performing regular endurance exercise. Of 128 eligible participants (mean ± SD = 64.3 ± 8.6 years), 113 had complete accelerometer data, which were used to determine daily step count. Multiple linear regression was used to identify factors associated with average daily step count over 10 days. Candidate explanatory variable categories were (1) demographics/anthropometrics, (2) Parkinson disease characteristics, (3) motor symptom severity, (4) nonmotor and behavioral characteristics, (5) comorbidities, and (6) cardiorespiratory fitness. Average daily step count was 5362 ± 2890 steps per day. Five factors explained 24% of daily step count variability, with higher step count associated with higher cardiorespiratory fitness (10%), no fear/worry of falling (5%), lower motor severity examination score (4%), more recent time since Parkinson disease diagnosis (3%), and the presence of a cardiovascular condition (2%). Daily step count in nonexercising people recruited for this intervention trial with de novo Parkinson disease approached sedentary lifestyle levels. Further study is warranted for elucidating factors explaining ambulatory activity, particularly cardiorespiratory fitness, and fear/worry of falling. Clinicians should consider the costs and benefits of exercise and activity behavior interventions immediately after diagnosis of Parkinson disease to attenuate the health consequences of low daily step count.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A170).

[Cell therapy for Parkinson's disease: IV. Risks and future trends].

PubMed

Anisimov, S V

2009-01-01

Motor dysfunctions in Parkinson's disease are believed to be primarily due to the degeneration of dopaminergic neurons located in the substantia nigra pars compacta. Numerous cell replacement therapy approaches have been developed and tested, including these based on donor cell transplantation (embryonic and adult tissue-derived), adult mesenchymal stem cells (hMSCs)-, neural stem cells (hNSCs)- and finally human embryonic stem cells (hESCs)-based. Despite the progress achieved, numerous difficulties prevent wider practical application of stem cell-based therapy approaches for the treatment of Parkinson's disease. Among the latter, ethical, safety and technical issues stand out. Current series of reviews (Cell therapy for Parkinson's disease: I. Embryonic and adult donor tissue-based applications; II. Adult stem cell-based applications; III. Neonatal, fetal and embryonic stem cell-based applications; IV. Risks and future trends) aims providing a balanced and updated view on various issues associated with cell types (including stem cells) in regards to their potential in the treatment of Parkinson's disease. Essential features of the individual cell subtypes, principles of available cell handling protocols, transplantation, and safety issues are discussed extensively.

Anaesthesia for Caesarean section in a patient with Parkinson's disease.

PubMed

Ward, V D

2018-05-01

Parkinson's disease is prevalent worldwide but mainly affects the elderly and is rarely seen in women of child-bearing age. The clinical signs and symptoms, the physiological changes of pregnancy, and drug interactions, pose unique challenges for the anaesthetic management of patients with Parkinson's disease who present for delivery. A 36-year-old primigravid woman at 36 weeks' gestation, with Parkinson's disease, presented for pre-anaesthesia assessment prior to elective caesarean section. Her Parkinson's disease had been diagnosed four years previously and was treated with Sinemet (levodopa/carbidopa) and pramipexole. Despite maximum allowable drug doses in pregnancy, she reported disease progression, with right-sided weakness in the upper and lower limbs and an altered gait. Spinal anaesthesia for elective Caesarean section was performed in the sitting position, using 0.5% hyperbaric bupivacaine, morphine 150 µg and fentanyl 25 µg. The anaesthesia and Caesarean section were uneventful. She was discharged home with a healthy baby on the fourth postoperative day. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Parkinson's disease death rate: carbidopa and vitamin B6.

PubMed

Hinz, Marty; Stein, Alvin; Cole, Ted

2014-01-01

The only indication for carbidopa and benserazide is the management of L-3,4-dihydroxyphenylalanine (L-dopa)-induced nausea. Both drugs irreversibly bind to and permanently deactivate pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, and PLP-dependent enzymes. PLP is required for the function of over 300 enzymes and proteins. Virtually every major system in the body is impacted directly or indirectly by PLP. The administration of carbidopa and benserazide potentially induces a nutritional catastrophe. During the first 15 years of prescribing L-dopa, a decreasing Parkinson's disease death rate was observed. Then, in 1976, 1 year after US Food and Drug Administration approved the original L-dopa/carbidopa combination drug, the Parkinson's disease death rate started increasing. This trend has continued to the present, for 38 years and counting. The previous literature documents this increasing death rate, but no hypothesis has been offered concerning this trend. Carbidopa is postulated to contribute to the increasing Parkinson's disease death rate and to the classification of Parkinson's as a progressive neurodegenerative disease. It may contribute to L-dopa tachyphylaxis.

Measuring the Burden of Hospitalization in Patients with Parkinson´s Disease in Spain.

PubMed

Gil-Prieto, Ruth; Pascual-Garcia, Raquel; San-Roman-Montero, Jesus; Martinez-Martin, Pablo; Castrodeza-Sanz, Javier; Gil-de-Miguel, Angel

2016-01-01

This epidemiological survey estimates the hospitalization burden related to Parkinson´s Disease in Spain. This observational retrospective survey was performed by reviewing data from the National Surveillance System for Hospital Data, which includes more than 98% of Spanish hospitals. All hospitalizations of patients with Parkinson´s disease that were reported from 1997-2012 were analyzed. Codes were selected using the 9th International Classification of Diseases: ICD-9-CM: 332.0. A total of 438,513 hospital discharges of patients with Parkinson´s Disease were reported during the study period. The annual hospitalization rate was 64.2 cases per 100,000. The average length of hospital stay was 10 days. The trend for the annual hospitalization rate differed significantly depending on whether Parkinson´s disease was the main cause of hospitalization (n = 23,086, 1.14% annual increase) or was not the main cause of hospitalization (n = 415,427, 15.37% annual increase). The overall case-fatality rate among hospitalized patients was 10%. The case fatality rate among patient´s hospitalized with Parkinson´s disease as the main cause of hospitalization was 2.5%. The hospitalization rate and case-fatality rate significantly increased with age. The primary causes of hospitalization when Parkinson´s disease was not coded as the main cause of hospitalization were as follows: respiratory system diseases (24%), circulatory system diseases (19%), injuries and poisoning, including fractures (12%), diseases of the digestive system (10%) and neoplasms (5%). The annual average cost for National Health Care System was € 120 M, with a mean hospitalization cost of €4,378. Parkinson´s disease poses a significant health threat in Spain, particularly in the elderly. While hospitalizations due to Parkinson´s Disease are relatively stable over time, the number of patients presenting with Parkinson´s disease as an important comorbidity has increased dramatically. Medical staff must

Pharmacological therapy of Parkinson's disease: current options and new avenues.

PubMed

Simola, Nicola; Pinna, Annalisa; Fenu, Sandro

2010-11-01

Parkinson's disease is a neurodegenerative pathology which affects the dopaminergic neurons in the mesencephalon, leading to a progressive and relentless motor disability and to non-motor symptoms of different severity. The aim of this review is to summarize the features of drugs currently used in the pharmacotherapy of Parkinson's disease, with a look at their beneficial effects and limitations. Drugs acting on dopamine transmission, as L-DOPA, direct dopaminergic agonists, inhibitors for either the MAO or COMT enzymes and drugs acting on neurotransmitters other than dopamine (e.g. acetylcholine, glutamate) will be covered. Investigational drugs currently under examination for their therapeutic potential in Parkinson's disease and recent patents which may be relevant to the field will be also discussed.

Stem cell transplantation for treating Parkinson's disease: Literature analysis based on the Web of Science.

PubMed

Li, Runhui

2012-06-05

To identify global research trends of stem cell transplantation for treating Parkinson's disease using a bibliometric analysis of the Web of Science. We performed a bibliometric analysis of data retrievals for stem cell transplantation for treating Parkinson's disease from 2002 to 2011 using the Web of Science. (a) peer-reviewed articles on stem cell transplantation for treating Parkinson's disease which were published and indexed in the Web of Science; (b) type of articles: original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material and news items; (c) year of publication: 2002-2011. (a) articles that required manual searching or telephone access; (b) we excluded documents that were not published in the public domain; (c) we excluded a number of corrected papers from the total number of articles. (1) Type of literature; (2) annual publication output; (3) distribution according to journals; (4) distribution according to subject areas; (5) distribution according to country; (6) distribution according to institution; (7) comparison of countries that published the most papers on stem cell transplantation from different cell sources for treating Parkinson's disease; (8) comparison of institutions that published the most papers on stem cell transplantation from different cell sources for treating Parkinson's disease in the Web of Science from 2002 to 2011; (9) comparison of studies on stem cell transplantation from different cell sources for treating Parkinson's disease. In total, 1 062 studies on stem cell transplantation for treating Parkinson's disease appeared in the Web of Science from 2002 to 2011, almost one third of which were from American authors and institutes. The number of studies on stem cell transplantation for treating Parkinson's disease had gradually increased over the past 10 years. Papers on stem cell transplantation for treating Parkinson's disease appeared in journals such as Stem Cells and

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

... Collection: Emergency Submission for OMB Review (Telehealth in the Parkinson's Disease Research, Education... needed to improve the care and clinical outcomes of patients with Parkinson's disease. DATES: Comments... Parkinson's Disease Research, Education and Clinical Center (PADRECC): The Key to the Patient-Centered...

Efficacy of community-based physiotherapy networks for patients with Parkinson's disease: a cluster-randomised trial.

PubMed

Munneke, Marten; Nijkrake, Maarten J; Keus, Samyra Hj; Kwakkel, Gert; Berendse, Henk W; Roos, Raymund Ac; Borm, George F; Adang, Eddy M; Overeem, Sebastiaan; Bloem, Bastiaan R

2010-01-01

Many patients with Parkinson's disease are treated with physiotherapy. We have developed a community-based professional network (ParkinsonNet) that involves training of a selected number of expert physiotherapists to work according to evidence-based recommendations, and structured referrals to these trained physiotherapists to increase the numbers of patients they treat. We aimed to assess the efficacy of this approach for improving health-care outcomes. Between February, 2005, and August, 2007, we did a cluster-randomised trial with 16 clusters (defined as community hospitals and their catchment area). Clusters were randomly allocated by use of a variance minimisation algorithm to ParkinsonNet care (n=8) or usual care (n=8). Patients were assessed at baseline and at 8, 16, and 24 weeks of follow-up. The primary outcome was a patient preference disability score, the patient-specific index score, at 16 weeks. Health secondary outcomes were functional mobility, mobility-related quality of life, and total societal costs over 24 weeks. Analysis was by intention to treat. This trial is registered, number NCT00330694. We included 699 patients. Baseline characteristics of the patients were comparable between the ParkinsonNet clusters (n=358) and usual-care clusters (n=341). The primary endpoint was similar for patients within the ParkinsonNet clusters (mean 47.7, SD 21.9) and control clusters (48.3, 22.4). Health secondary endpoints were also similar for patients in both study groups. Total costs over 24 weeks were lower in ParkinsonNet clusters compared with usual-care clusters (difference euro727; 95% CI 56-1399). Implementation of ParkinsonNet networks did not change health outcomes for patients living in ParkinsonNet clusters. However, health-care costs were reduced in ParkinsonNet clusters compared with usual-care clusters. ZonMw; Netherlands Organisation for Scientific Research; Dutch Parkinson's Disease Society; National Parkinson Foundation; Stichting Robuust

Physiotherapy intervention in Parkinson's disease: systematic review and meta-analysis.

PubMed

Tomlinson, Claire L; Patel, Smitaa; Meek, Charmaine; Herd, Clare P; Clarke, Carl E; Stowe, Rebecca; Shah, Laila; Sackley, Catherine; Deane, Katherine H O; Wheatley, Keith; Ives, Natalie

2012-08-06

To assess the effectiveness of physiotherapy compared with no intervention in patients with Parkinson's disease. Systematic review and meta-analysis of randomised controlled trials. Literature databases, trial registries, journals, abstract books, and conference proceedings, and reference lists, searched up to the end of January 2012. Randomised controlled trials comparing physiotherapy with no intervention in patients with Parkinson's disease were eligible. Two authors independently abstracted data from each trial. Standard meta-analysis methods were used to assess the effectiveness of physiotherapy compared with no intervention. Tests for heterogeneity were used to assess for differences in treatment effect across different physiotherapy interventions used. Outcome measures were gait, functional mobility and balance, falls, clinician rated impairment and disability measures, patient rated quality of life, adverse events, compliance, and economic analysis outcomes. 39 trials of 1827 participants met the inclusion criteria, of which 29 trials provided data for the meta-analyses. Significant benefit from physiotherapy was reported for nine of 18 outcomes assessed. Outcomes which may be clinically significant were speed (0.04 m/s, 95% confidence interval 0.02 to 0.06, P<0.001), Berg balance scale (3.71 points, 2.30 to 5.11, P<0.001), and scores on the unified Parkinson's disease rating scale (total score -6.15 points, -8.57 to -3.73, P<0.001; activities of daily living subscore -1.36, -2.41 to -0.30, P=0.01; motor subscore -5.01, -6.30 to -3.72, P<0.001). Indirect comparisons of the different physiotherapy interventions found no evidence that the treatment effect differed across the interventions for any outcomes assessed, apart from motor subscores on the unified Parkinson's disease rating scale (in which one trial was found to be the cause of the heterogeneity). Physiotherapy has short term benefits in Parkinson's disease. A wide range of physiotherapy techniques

The characteristics of autonomic nervous system disorders in burning mouth syndrome and Parkinson disease.

PubMed

Koszewicz, Magdalena; Mendak, Magdalena; Konopka, Tomasz; Koziorowska-Gawron, Ewa; Budrewicz, Sławomir

2012-01-01

To conduct a clinical electrophysiologic evaluation of autonomic nervous system functions in patients with burning mouth syndrome and Parkinson disease and estimate the type and intensity of the autonomic dysfunction. The study involved 83 subjects-33 with burning mouth syndrome, 20 with Parkinson disease, and 30 controls. The BMS group included 27 women and 6 men (median age, 60.0 years), and the Parkinson disease group included 15 women and 5 men (median age, 66.5 years). In the control group, there were 20 women and 10 men (median age, 59.0 years). All patients were subjected to autonomic nervous system testing. In addition to the Low autonomic disorder questionnaire, heart rate variability (HRV), deep breathing (exhalation/inspiration [E/I] ratio), and sympathetic skin response (SSR) tests were performed in all cases. Parametric and nonparametric tests (ANOVA, Kruskal-Wallis, and Scheffe tests) were used in the statistical analysis. The mean values for HRV and E/I ratios were significantly lower in the burning mouth syndrome and Parkinson disease groups. Significant prolongation of SSR latency in the foot was revealed in both burning mouth syndrome and Parkinson disease patients, and lowering of the SSR amplitude occurred in only the Parkinson disease group. The autonomic questionnaire score was significantly higher in burning mouth syndrome and Parkinson disease patients than in the control subjects, with the Parkinson disease group having the highest scores. In patients with burning mouth syndrome, a significant impairment of both the sympathetic and parasympathetic nervous systems was found but sympathetic/parasympathetic balance was preserved. The incidence and intensity of autonomic nervous system dysfunction was similar in patients with burning mouth syndrome and Parkinson disease, which may suggest some similarity in their pathogeneses.

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

Orthostatic hypotension acutely impairs executive functions in Parkinson's disease.

PubMed

Sforza, Michela; Assogna, Francesca; Rinaldi, Domiziana; Sette, Giuliano; Tagliente, Stefania; Pontieri, Francesco E

2018-04-07

Orthostatic hypotension is a frequent non-motor symptom of Parkinson's disease, with negative prognostic role on cognitive functions. Here we measured the acute effects of orthostatic hypotension on executive functions in Parkinson's disease patients devoid of hypertension, carotid artery stenosis, and significant chronic cerebrovascular pathology. Measurements were carried out during regular visits in outpatient setting. Twenty-eight Parkinson's disease patients were recruited and studied along scheduled outpatient visits. They were divided into two groups (n = 14 each) based on the presence or lack of orthostatic hypotension. This was diagnosed according to international guidelines. All patients were submitted to the Stroop's test and to the phonological and semantic verbal fluency test after 10-min resting in supine position and immediately upon standing in upright position. Testing lasted less than 5 min in either position. In upright position, subjects with orthostatic hypotension displayed significantly worse performances at the Stroop's test word reading time (22.1 ± 4.1 vs. 14.9 ± 4.0 s), interference time (56.1 ± 12.3 vs. 41.4 ± 11.8 s), and number of errors at the interference section (5.8 ± 3.2 vs. 1.3 ± 2.1) as compared to those without orthostatic hypotension. These results demonstrate that worsening of attentive function upon standing can be measured in Parkinson's disease patients with orthostatic hypotension during routine outpatient visits. These findings suggest that clinically asymptomatic orthostatic hypotension in Parkinson's disease patients may acutely worsen neuropsychological performances with possible negative impact on daily functioning.

Risk of Parkinson's disease following zolpidem use: a retrospective, population-based cohort study.

PubMed

Huang, Hui-Chun; Tsai, Chon-Haw; Muo, Chih-Hsin; Lin, Kang-Hsu; Lu, Ming-Kuei; Sung, Fung-Chang; Kao, Chia-Hung

2015-01-01

To evaluate the influence of long-term zolpidem use on the incidence of developing Parkinson's disease. 2,961 subjects who used zolpidem for the first time longer than 3 months between 1998 and 2000 were identified in the National Health Insurance system of Taiwan. Subjects without a history of zolpidem use were randomly selected as a comparison cohort and frequency matched to zolpidem users based on age, sex, and index date. The diagnosis of Parkinson's disease was based on the criteria of the International Classification of Diseases, Ninth Revision, Clinical Modification. Its incidence until the end of 2009 was calculated and its hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression models and Kaplan-Meier analysis. The overall incidence of Parkinson's disease was greater among zolpidem users than in the comparison cohort (HR = 1.88; 95% CI, 1.45-2.45). However, there was no difference in Parkinson's disease incidence between these 2 cohorts after 5 years of observation. The risk of Parkinson's disease increased with increasing zolpidem dose, with an HR of 0.70 for low-dose users (< 400 mg/y) and 2.94 for high-dose users (≥ 1,600 mg/y). The incidence of Parkinson's disease was greater in subjects using zolpidem only (HR = 2.35; 95% CI, 1.66-3.33) compared to those using benzodiazepines only (HR = 1.31; 95% CI, 0.91-1.90). By stratified analysis, zolpidem use with concurrent depression (HR = 4.79) increased the risk of Parkinson's disease compared to that of zolpidem users without concurrent depression. Zolpidem use might unmask preclinical Parkinson's disease, especially in patients with depression. However, large population-based, unbiased, randomized trials are warranted to confirm this finding. © Copyright 2015 Physicians Postgraduate Press, Inc.

Living with advanced Parkinson's disease: a constant struggle with unpredictability.

PubMed

Haahr, Anita; Kirkevold, Marit; Hall, Elisabeth O C; Ostergaard, Karen

2011-02-01

This paper is a report of an exploration of patients' lifeworld and way of managing life with advanced Parkinson's disease prior to Deep Brain Stimulation and what they expect from life following this treatment. Parkinson's disease is a progressive neurodegenerative disease, which is initially well-treated with L-dopa. Living with Parkinson's disease means living with the experience of continuous loss of independence and self-esteem and unpredictable ON/OFF phenomena. Thus, in the advanced stage of the disease, treatment with Deep Brain Stimulation may become relevant. Eleven patients eligible for Deep Brain Stimulation were interviewed prior to treatment. Data were collected in 2007 and analysed according to the hermeneutic phenomenological methodology of van Manen, using the four existentials as analytic tools. Living with advanced Parkinson's disease can be described as the experience of living with and managing unpredictability. The disease gradually took over, and participants had to struggle with unpredictability on a daily basis. Themes in relation to this were: The body - setting the agenda, Always a struggle to be on time, Living in dependence and compromise - being a burden, and Living with restrained space and changes in social life. Parkinson's disease leads to profound bodily restrictions. Living with an unpredictable body affects all aspects of life, and nurses need to be aware of the impact the disease has on the entire lifeworld, and how this may affect the way treatment is perceived. © 2010 Blackwell Publishing Ltd.

Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease.

PubMed

Gunay, Mine Silindir; Ozer, A Yekta; Chalon, Sylvie

2016-01-01

Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson's disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α -synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson's disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson's Disease therapy and reduce its side effects.

Dyskinesia in Parkinson's disease: mechanisms and current non-pharmacological interventions.

PubMed

Heumann, Rolf; Moratalla, Rosario; Herrero, Maria Trinidad; Chakrabarty, Koushik; Drucker-Colín, René; Garcia-Montes, Jose Ruben; Simola, Nicola; Morelli, Micaela

2014-08-01

Dopamine replacement therapy in Parkinson's disease is associated with several unwanted effects, of which dyskinesia is the most disabling. The development of new therapeutic interventions to reduce the impact of dyskinesia in Parkinson's disease is therefore a priority need. This review summarizes the key molecular mechanisms that underlie dyskinesia. The role of dopamine receptors and their associated signaling mechanisms including dopamine-cAMP-regulated neuronal phosphoprotein, extracellular signal-regulated kinase, mammalian target of rapamycin, mitogen and stress-activated kinase-1 and Histone H3 are summarized, along with an evaluation of the role of cannabinoid and nicotinic acetylcholine receptors. The role of synaptic plasticity and animal behavioral results on dyskinesia are also evaluated. The most recent therapeutic advances to treat Parkinson's disease are discussed, with emphasis on the possibilities and limitations of non-pharmacological interventions such as physical activity, deep brain stimulation, transcranial magnetic field stimulation and cell replacement therapy. The review suggests new prospects for the management of Parkinson's disease-associated motor symptoms, especially the development of dyskinesia. This review aims at summarizing the key molecular mechanisms underlying dyskinesia and the most recent therapeutic advances to treat Parkinson's disease with emphasis on non-pharmacological interventions such as physical activity, deep brain stimulation (DBS), transcranial magnetic field stimulation (TMS) and cell replacement therapy. These new interventions are discussed from both the experimental and clinical point of view, describing their current strength and limitations. © 2014 International Society for Neurochemistry.

"Think positively": Parkinson's disease, biomedicine, and hope in contemporary Germany.

PubMed

Metzler, Ingrid; Just, Paul

2017-06-01

Narratives of hope shape contemporary engagements with Parkinson's disease. On the one hand, a "biomedical narrative of hope" promises that biomedical research will help to transform this treatable but incurable disease into a curable one in the future. On the other hand, a more individual "illness narrative of hope" encourages patients to influence the course of Parkinson's disease by practicing self-care and positive thinking. This article asks how these two narratives of hope interact. It bases its argument on an analysis of data from 13 focus groups conducted in Germany in 2012 and 2014 with patients with Parkinson's disease and their relatives. Participants were asked to have their say on clinical trials for advanced therapies for Parkinson's disease and, while doing so, envisioned their biosocial selves in the present and the future. Three "modes of being" for patients were drawn from this body of data: a "users on stand-by" mode, an "unengaged" mode, and an "experimental pioneers" mode. Both narratives of hope were important to all three modes, yet they were mobilized at different frequencies and also had different statuses. While the biomedical narrative of hope was deemed an important "dream of the future" that participants passively supported without having to make it their own, the illness narrative of hope was a truth discourse that took an imperative form: having Parkinson's disease implied the need to maintain a positive attitude.

[Inferior frontal region hypoperfusion in Parkinson disease with dementia].

PubMed

Ochudło, Stanisław; Opala, Grzegorz; Jasińska-Myga, Barbara; Siuda, Joanna; Nowak, Stanisław

2003-01-01

Dementia is more frequent in patients suffering from Parkinson's disease (PD) then in general population. The mechanism for mental deterioration in PD remains controversial. The aim of our study was comparison of the regional cerebral perfusion quantified by single photon emission computed tomography in patients suffering from idiopathic Parkinson's disease with and without dementia. We examined 49 PD patients: 22 PD patients with dementia and 27 PD patients without dementia. Dementia was recognized according to ICD-10 and DSM-IV criteria. Cognitive functions were executed by means of the Mini Mental State Examination (MMSE) and neuropsychological assessment. The Unified Parkinson's Disease Rating Scale (UPDRS) and Modified Hoehn & Yahr Scale was used to quantify the severity of PD. SPECT was performed with Siemens Diacam single--head rotating gamma camera after intravenous application of technetium 99m hexamethylpropylene amine oxime (99mTc-HMPAO). The perfusion values were expressed as cortical or basal ganglia regions of interest (ROIs)/cerebellum activity ratios. In both examined group of patients the lowest uptake was in basal ganglia region, while the highest uptake was in occipital region. In the subgroup of PD patients with dementia significant hypoperfusion affecting the inferior frontal cortices was observed. In Parkinson's disease with dementia hypoperfusion in inferior frontal region can be found.

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…

Role of Neurotrophic Factors in Parkinson's Disease.

PubMed

Tome, Diogo; Fonseca, Carla Pais; Campos, Filipa Lopes; Baltazar, Graca

2017-01-01

Parkinson's disease is an age-associated progressive neurodegenerative disorder that has gained crescent social and economic impact due to the aging of the western society. All current therapies are symptomatic and fail to reverse or halt the progression of dopaminergic neurons loss. The discovery of the capability of neurotrophic factors to protect these neurons lead numerous research groups to focus their efforts in developing therapies aiming at promoting the control of Parkinson´s disease through the delivery of neurotrophic factors to the brain or by boosting their endogenous levels. Both strategies were successful in inducing protection of dopaminergic neurons and motor recovery in preclinical models of the disease. Contrariwise, very limited success was obtained in clinical studies, where glial cell line-derived neurotrophic factor and neurturin were the neurotrophic factors of choice for Parkinson's disease therapy. These drawbacks motivate the development of novel forms of delivery or the modification of the injected molecules aiming at providing a more stable and effective administration with improved diffusion in the target tissue, and without the immune responses observed in the earliest clinical studies. Although promising results were obtained with some of these new approaches performed in experimental models of the disease, they were not yet tested in human studies. In this review, we present the current knowledge on neurotrophic factors and their role in Parkinson's disease, focusing on the strategies that have been developed to increase their levels in target areas of the brain to achieve protection of dopaminergic neurons and motor behaviour recovery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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. © 2016 International Parkinson and Movement Disorder

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

Electroconvulsive therapy in Parkinson's disease.

PubMed

Calderón-Fajardo, Humberto; Cervantes-Arriaga, Amin; Llorens-Arenas, Rodrigo; Ramírez-Bermudez, Jesús; Ruiz-Chow, Ángel; Rodríguez-Violante, Mayela

2015-10-01

Purpose To analyze the effectiveness of electroconvulsive therapy for the management of depression and/or psychosis refractory to drug therapy in patients with Parkinson disease.Methods A retrospective study was carried out including patients treated with electroconvulsive therapy during the period between 2002 and 2013. A review of the literature was performed.Results A total of 27 patients were included. In regards to the neuropsychiatric diagnosis, 14 patients had major depression, 12 patients had both psychosis and depression, and only one patient had isolated psychosis. The mean number of electroconvulsive therapy sessions was 12 ± 2.8. After electroconvulsive therapy, all patients showed a statistically significant improvement in the Brief Psychiatric Rating scale (reduction of 52% points) and Hamilton Depression Rating Scale (reduction of 50% points) independent of the presence of psychosis, depression or both.Conclusion Electroconvulsive therapy is effective for the treatment of refractory neuropsychiatric symptoms in Parkinson's disease.

Parkinson's disease and Parkinson's disease medications have distinct signatures of the gut microbiome.

PubMed

Hill-Burns, Erin M; Debelius, Justine W; Morton, James T; Wissemann, William T; Lewis, Matthew R; Wallen, Zachary D; Peddada, Shyamal D; Factor, Stewart A; Molho, Eric; Zabetian, Cyrus P; Knight, Rob; Payami, Haydeh

2017-05-01

There is mounting evidence for a connection between the gut and Parkinson's disease (PD). Dysbiosis of gut microbiota could explain several features of PD. The objective of this study was to determine if PD involves dysbiosis of gut microbiome, disentangle effects of confounders, and identify candidate taxa and functional pathways to guide research. A total of 197 PD cases and 130 controls were studied. Microbial composition was determined by 16S rRNA gene sequencing of DNA extracted from stool. Metadata were collected on 39 potential confounders including medications, diet, gastrointestinal symptoms, and demographics. Statistical analyses were conducted while controlling for potential confounders and correcting for multiple testing. We tested differences in the overall microbial composition, taxa abundance, and functional pathways. Independent microbial signatures were detected for PD (P = 4E-5), participants' region of residence within the United States (P = 3E-3), age (P = 0.03), sex (P = 1E-3), and dietary fruits/vegetables (P = 0.01). Among patients, independent signals were detected for catechol-O-methyltransferase-inhibitors (P = 4E-4), anticholinergics (P = 5E-3), and possibly carbidopa/levodopa (P = 0.05). We found significantly altered abundances of the Bifidobacteriaceae, Christensenellaceae, [Tissierellaceae], Lachnospiraceae, Lactobacillaceae, Pasteurellaceae, and Verrucomicrobiaceae families. Functional predictions revealed changes in numerous pathways, including the metabolism of plant-derived compounds and xenobiotics degradation. PD is accompanied by dysbiosis of gut microbiome. Results coalesce divergent findings of prior studies, reveal altered abundance of several taxa, nominate functional pathways, and demonstrate independent effects of PD medications on the microbiome. The findings provide new leads and testable hypotheses on the pathophysiology and treatment of PD. © 2017 International Parkinson and Movement Disorder Society. © 2017

The Identification of Alpha-Synuclein as the First Parkinson Disease Gene

PubMed Central

Nussbaum, Robert L.

2017-01-01

In this Commentary, I describe the events that led from an NINDS-sponsored Workshop on Parkinson Disease Research in 1995, where I was asked to speak about the genetics of Parkinson disease, to the identification a mere two years later of a mutation in alpha-synuclein as the cause of autosomal dominant Parkinson disease in the Contursi kindred. I review the steps we took to first map and then find the mutation in the alpha-synuclein locus and describe the obstacles and the role of serendipity in facilitating the work. Although alpha-synuclein mutations are a rare cause of hereditary PD, the importance of this finding goes far beyond the rare families with hereditary disease because it pinpointed alpha-synuclein as a key contributor to the far more common sporadic form of Parkinson disease. This work confirms William Harvey’s observation from 350 years ago that studying rarer forms of a disease is an excellent way to understand the more common forms of that disease. The identification of synuclein’s role in hereditary Parkinson disease has opened new avenues of research into the pathogenesis and potential treatments of the common form of Parkinson disease that affects many millions of Americans and tens of millions of human beings worldwide. PMID:28282812

The Identification of Alpha-Synuclein as the First Parkinson Disease Gene.

PubMed

Nussbaum, Robert L

2017-01-01

In this Commentary, I describe the events that led from an NINDS-sponsored Workshop on Parkinson Disease Research in 1995, where I was asked to speak about the genetics of Parkinson disease, to the identification a mere two years later of a mutation in alpha-synuclein as the cause of autosomal dominant Parkinson disease in the Contursi kindred. I review the steps we took to first map and then find the mutation in the alpha-synuclein locus and describe the obstacles and the role of serendipity in facilitating the work. Although alpha-synuclein mutations are a rare cause of hereditary PD, the importance of this finding goes far beyond the rare families with hereditary disease because it pinpointed alpha-synuclein as a key contributor to the far more common sporadic form of Parkinson disease. This work confirms William Harvey's observation from 350 years ago that studying rarer forms of a disease is an excellent way to understand the more common forms of that disease. The identification of synuclein's role in hereditary Parkinson disease has opened new avenues of research into the pathogenesis and potential treatments of the common form of Parkinson disease that affects many millions of Americans and tens of millions of human beings worldwide.

The use of rasagiline in Parkinson's disease.

PubMed

Schapira, A H V

2006-01-01

Rasagiline is a novel, potent, irreversible inhibitor of monoamine oxidative B developed for the symptomatic treatment of Parkinson's disease. The drug has shown efficacy in improving motor features in both early and advanced Parkinson's disease patients. The drug appears to be well tolerated and its once daily fixed dose formulation should make for excellent compliance. Rasagiline has also demonstrated important neuroprotective properties in both in vitro and in vivo laboratory studies. A provisional study of neuroprotection in a delayed start clinical trial of early PD patients has also suggested that this benefit may be translated to the clinic. Additional clinical trials are underway to confirm this.

[Dopamine agonists--clinical applications beyond Parkinson's disease].

PubMed

Kuran, Włodzimierz

2007-01-01

Contemporary experience and results of clinical trials concerning dopamine agonist application in the treatment of many different diseases (apart from Parkinson's disease) are presented in the paper. A basic clinical recommendation for agonists is restless legs syndrome. In this syndrome almost all agonists give a considerable subjective and objective improvement. Treatment of atypical parkinsonism (MSA, PSP, CBD) in the majority of patients is ineffective. The author also presents promising results of treatment with agonists in such diverse diseases as hyperkinetic syndromes, cocaine dependence, drug-resistant depression and erectile dysfunction (apomorphine). Dopamine partial agonists (e.g. aripiprazol) are recommended in the modern treatment of schizophrenia.

Development of Parkinson Patient Generated Data Collection Platform Using FHIR and IoT Devices.

PubMed

Kim, Dae-Young; Hwang, Sun-Ho; Kim, Min-Gyu; Song, Joon-Hyun; Lee, Sin-Woong; Kim, Il Kon

2017-01-01

Internet of Things (IoT) devices can be effectively used in cases where continuous observation of patients is required, such as Parkinson's disease. This is due to the characteristics of the IoT (Internet of Things), which allows data to be measured and transmitted at any time, anywhere. In this study, we developed a health data collection platform that stores and transmits the foot pressure data of Parkinson patients using FHIR (Fast Healthcare Interoperability Resources). The platform can be used to collect the foot pressure of a large number of Parkinson's patients. Based on the accumulated data, it is possible to identify abnormal behaviors such as walking pattern, tilt and instability of stride length in patients with Parkinson's disease. Based on the results of this study, accurate diagnosis and treatment of Parkinson's disease can be made.

Increased muscle belly and tendon stiffness in patients with Parkinson's disease, as measured by myotonometry.

PubMed

Marusiak, Jarosław; Jaskólska, Anna; Budrewicz, Sławomir; Koszewicz, Magdalena; Jaskólski, Artur

2011-09-01

Based on Davis's law, greater tonus of the muscle belly in individuals with Parkinson's disease can create greater tension in the tendon, leading to structural adjustment and an increase in tendon stiffness. Our study aimed to separately assess passive stiffness in the muscle belly and tendon in medicated patients with Parkinson's disease, using myotonometry. We tested 12 patients with Parkinson's disease and 12 healthy matched controls. Passive stiffness of muscle belly and tendon was estimated by myotonometry, electromyography, and mechanomyography in relaxed biceps and triceps brachii muscles. Compared with controls, patients with Parkinson's disease had higher stiffness in the muscle belly and tendon of the biceps brachii and in the tendon of the triceps brachii. In patients with Parkinson's disease, there was a positive correlation between muscle belly stiffness and parkinsonian rigidity in the biceps brachii. Patients with Parkinson's disease have higher passive stiffness of the muscle belly and tendon than healthy matched controls. Copyright © 2011 Movement Disorder Society.

Parkinson's Disease Diagnostic Observations (PADDO): study rationale and design of a prospective cohort study for early differentiation of parkinsonism.

PubMed

van Rumund, Anouke; Aerts, Marjolein B; Esselink, Rianne A J; Meijer, Frederick J A; Verbeek, Marcel M; Bloem, Bastiaan R

2018-05-16

Differentiation of Parkinson's disease (PD) from the various types of atypical parkinsonism (AP) such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), corticobasal syndrome (CBS) and vascular parkinsonism (VP), can be challenging, especially early in the disease course when symptoms overlap. A major unmet need in the diagnostic workup of these disorders is a diagnostic tool that differentiates the various disorders, preferably in the earliest disease stages when the clinical presentation is similar. Many diagnostic tests have been evaluated, but their added value was studied mostly in retrospective case-control studies that included patients with a straightforward clinical diagnosis. Here, we describe the design of a prospective cohort study in patients with parkinsonism in an early disease stage who have an uncertain clinical diagnosis. Our aim is to evaluate the diagnostic accuracy of (1) detailed clinical examination by a movement disorder specialist, (2) magnetic resonance imaging (MRI) techniques and (3) cerebrospinal fluid (CSF) biomarkers. Patients with parkinsonism with an uncertain clinical diagnosis and a disease course less than three years will be recruited. Patients will undergo extensive neurological examination, brain MRI including conventional and advanced sequences, and a lumbar puncture. The diagnosis (including level of certainty) will be defined by a movement disorders expert, neuroradiologist and neurochemist based on clinical data, MRI results and CSF results, respectively. The clinical diagnosis after three years' follow-up will serve as the "gold standard" reference diagnosis, based on consensus criteria and as established by two movement disorder specialists (blinded to the test results). Diagnostic accuracy of individual instruments and added value of brain MRI and CSF analysis after evaluation by a movement disorder expert will be calculated, expressed as the change in percentage of

Clinical subtypes and genetic heterogeneity: of lumping and splitting in Parkinson disease.

PubMed

von Coelln, Rainer; Shulman, Lisa M

2016-12-01

Recent studies on clinical, genetic and pathological heterogeneity of Parkinson disease have renewed the old debate whether we should think of Parkinson disease as one disease with variations, or as a group of independent diseases that happen to present with similar phenotypes. Here, we provide an overview of where the debate is coming from, and how recent findings in clinical subtyping, genetics and clinico-pathological correlation have shaped this controversy over the last few years. New and innovative clinical diagnostic criteria for Parkinson disease have been proposed and await validation. Studies using functional imaging or wearable biosensors, as well as biomarker studies, provide new support for the validity of the traditional clinical subtypes of Parkinson disease (tremor-dominant versus akinetic-rigid or postural instability/gait difficulty). A recent cluster analysis (as unbiased data-driven approach to subtyping) included a wide spectrum of nonmotor variables, and showed correlation of the proposed subtypes with disease progression in a longitudinal analysis. New genetic factors contributing to Parkinson disease susceptibility continue to be identified, including rare mutations causing monogenetic disease, common variants with small effect size and risk factors (like mutations in the gene for glucocerebrosidase) that fall in between the two other categories. Recent studies show some limited correlation between genetic factors and clinical heterogeneity. Despite some variations in patterns of pathology, Lewy bodies are still the hallmark of Parkinson disease, including the vast majority of genetic subgroups. Evidence of clinical, genetic and pathological heterogeneity of Parkinson disease continues to emerge, but clearly defined subtypes that hold up in more than one of these domains remain elusive. For research to identify such subtypes, splitting is likely the way forward; until then, for clinical practice, lumping remains the more pragmatic approach.

Integrative network analysis unveils convergent molecular pathways in Parkinson's disease and diabetes.

PubMed

Santiago, Jose A; Potashkin, Judith A

2013-01-01

Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level. Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP), previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS) and the Prognostic Biomarker Study (PROBE), revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients. These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first time that

Quality of life in patients with Parkinson's disease: development of a questionnaire.

PubMed Central

de Boer, A G; Wijker, W; Speelman, J D; de Haes, J C

1996-01-01

OBJECTIVES--To develop and test a questionnaire for measuring quality of life in patients with Parkinson's disease. METHODS--An item pool was developed based on the experience of patients with Parkinson's disease and of neurologists; medical literature on the problems of patients with Parkinson's disease; and other quality of life questionnaires. To reduce the item pool, 13 patients identified items that were a problem to them and rated their importance. Items which were most often chosen and rated most important were included in the Parkinson's disease quality of life questionnaire (PDQL). The PDQL consists of 37 items. To evaluate the discriminant validity of the PDQL three groups of severity of disease were compared. To test for convergent validity, the scores of the PDQL were tested for correlation with standard indices of quality of life. RESULTS--The PDQL was filled out by 384 patients with Parkinson's disease. It consisted of four subscales: parkinsonian symptoms, systemic symptoms, emotional functioning, and social functioning. The internal-consistency reliability coefficients of the PDQL subscales were high (0.80-0.87). Patients with higher disease severity had significantly lower quality of life on all PDQL subscales (P < 0.05). Almost all PDQL subscales correlated highly (P < 0.001) with the corresponding scales of the standard quality of life indices. CONCLUSION--The PDQL is a relevant, reliable, and valid measure of the quality of life of patients with Parkinson's disease. Images PMID:8676165

Impulse control disorders are associated with multiple psychiatric symptoms in Parkinson's disease.

PubMed

Jaakkola, Elina; Kaasinen, Valtteri; Siri, Chiara; Martikainen, Kirsti; Cilia, Roberto; Niemelä, Solja; Joutsa, Juho

2014-01-01

Impulse control disorders can have serious adverse consequences to the life of a patient with Parkinson's disease. Although impulse control disorders are common, a possible psychiatric comorbidity has not been fully characterized. The aim of this study was to investigate the psychiatric symptoms exhibited by Parkinson's disease patients with impulse control disorders. The study was conducted as a postal survey to patients in the registry of the Finnish Parkinson Association. A total of 290 Parkinson's disease patients were evaluated for impulse control disorders using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease. Psychiatric symptoms were systematically screened using the Symptom Checklist 90. We found that 108 of the evaluated patients had one or more impulse control disorders. Patients with impulse control disorders had markedly higher scores for symptoms of psychoticism (Bonferroni corrected p < 0.001), interpersonal sensitivity (p < 0.001), obsessive-compulsive disorder (p < 0.001), and depression (p = 0.01) when compared with patients without impulse control disorders. Impulse control disorders were shown to be independently associated with these symptoms. Patients with multiple impulse control disorders had higher scores for depression and obsessive-compulsive symptoms when compared with patients that exhibited only one impulse control disorder. COUNCLUSIONS: Our results confirm the previous observations that impulse control disorders in Parkinson's disease are linked with multiple psychiatric symptoms, including psychoticism, interpersonal sensitivity, obsessive-compulsive symptoms and depression. Clinicians treating these patients should acknowledge the concomitant psychiatric symptoms.

[Emotion and basal ganglia (I): what can we learn from Parkinson's disease?].

PubMed

Dondaine, T; Péron, J

2012-01-01

Parkinson's disease provides a useful model for studying the neural substrates of emotional processing. The striato-thalamo-cortical circuits, like the mesolimbic dopamine system that modulates their function, are thought to be involved in emotional processing. As Parkinson's disease is histopathologically characterized by the selective, progressive and chronic degeneration of the nigrostriatal and mesocorticolimbic dopamine systems, it can therefore serve as a model for assessing the functional role of these circuits in humans. In the present review, after a definition of emotional processing from a multicomponential perspective, a synopsis of the emotional disturbances observed in Parkinson's disease is proposed. Note that the studies on the affective consequences of subthalamic nucleus deep brain stimulation in Parkinson's disease were excluded from this review because the subject of a companion paper in this issue. This review leads to the conclusion that several emotional components would be disrupted in Parkinson's disease: subjective feeling, neurophysiological activation, and motor expression. We then discuss the functional roles of the striato-thalamo-cortical and mesolimbic circuits, ending with the conclusion that both these pathways are indeed involved in emotional processing. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment.

PubMed

Schneider, Christine B; Donix, Markus; Linse, Katharina; Werner, Annett; Fauser, Mareike; Klingelhoefer, Lisa; Löhle, Matthias; von Kummer, Rüdiger; Reichmann, Heinz; Storch, Alexander

2017-09-01

Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. Irrespective of the study participants' cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.

Geographic and Ethnic Variation in Parkinson Disease: A Population-Based Study of US Medicare Beneficiaries

PubMed Central

Wright Willis, Allison; Evanoff, Bradley A.; Lian, Min; Criswell, Susan R.; Racette, Brad A.

2010-01-01

Background Parkinson disease is a common neurodegenerative disease. The racial, sex, age, and geographic distributions of Parkinson disease in the US are unknown. Methods We performed a serial cross-sectional study of US Medicare beneficiaries aged 65 and older from the years 1995, and 2000–2005. Using over 450,000 Parkinson disease cases per year, we calculated Parkinson disease prevalence and annual incidence by race, age, sex, and county. Spatial analysis investigated the geographic distribution of Parkinson disease. Results Age-standardized Parkinson disease prevalence (per 100,000) was 2,168.18 (±95.64) in White men, but 1,036.41 (±86.01) in Blacks, and 1,138.56 (±46.47) in Asians. The incidence ratio in Blacks as compared to Whites (0.74; 95% CI = 0.732–0.748) was higher than the prevalence ratio (0.58; 95% CI = 0.575–0.581), whereas the incidence ratio for Asians (0.69; 95% CI = 0.657–0.723) was similar to the prevalence ratio (0.62; 95% CI = 0.617–0.631). Bayesian mapping of Parkinson disease revealed a concentration in the Midwest and Northeast regions. Mean county incidence by quartile ranged from 279 to 3,111, and prevalence from 1,175 to 13,800 (per 100,000). Prevalence and incidence in urban counties were greater than in rural ones (p < 0.01). Cluster analysis supported a nonrandom distribution of both incident and prevalent Parkinson disease cases (p < 0.001). Conclusions Parkinson disease is substantially more common in Whites, and is nonrandomly distributed in the Midwest and Northeastern US. PMID:20090375

Mood changes following social dance sessions in people with Parkinson's disease.

PubMed

Lewis, Carine; Annett, Lucy E; Davenport, Sally; Hall, Amelia A; Lovatt, Peter

2016-04-01

Dance interventions have physical benefits for the elderly, especially those with Parkinson's disease. This study assessed the psychological benefits of dance. A total of 37 participants, with either Parkinson's disease (n= 22) or age-matched controls (n= 15) completed mood questionnaires before and after a 10-week dance intervention. An overall reduction in total mood disturbance and a specific reduction in anger were observed. In addition, less fatigue was found for those initially scoring higher in depression. This suggests that dance can provide psychological benefits for both people with Parkinson's disease and the elderly, with findings suggesting that this is an avenue to be explored further. © The Author(s) 2014.

Measuring the Burden of Hospitalization in Patients with Parkinson´s Disease in Spain

PubMed Central

Gil-Prieto, Ruth; Pascual-Garcia, Raquel; San-Roman-Montero, Jesus; Martinez-Martin, Pablo; Castrodeza-Sanz, Javier; Gil-de-Miguel, Angel

2016-01-01

Introduction This epidemiological survey estimates the hospitalization burden related to Parkinson´s Disease in Spain. Methods This observational retrospective survey was performed by reviewing data from the National Surveillance System for Hospital Data, which includes more than 98% of Spanish hospitals. All hospitalizations of patients with Parkinson´s disease that were reported from 1997–2012 were analyzed. Codes were selected using the 9th International Classification of Diseases: ICD-9-CM: 332.0. Results A total of 438,513 hospital discharges of patients with Parkinson´s Disease were reported during the study period. The annual hospitalization rate was 64.2 cases per 100,000. The average length of hospital stay was 10 days. The trend for the annual hospitalization rate differed significantly depending on whether Parkinson´s disease was the main cause of hospitalization (n = 23,086, 1.14% annual increase) or was not the main cause of hospitalization (n = 415,427, 15.37% annual increase). The overall case-fatality rate among hospitalized patients was 10%. The case fatality rate among patient´s hospitalized with Parkinson´s disease as the main cause of hospitalization was 2.5%. The hospitalization rate and case-fatality rate significantly increased with age. The primary causes of hospitalization when Parkinson´s disease was not coded as the main cause of hospitalization were as follows: respiratory system diseases (24%), circulatory system diseases (19%), injuries and poisoning, including fractures (12%), diseases of the digestive system (10%) and neoplasms (5%). The annual average cost for National Health Care System was € 120 M, with a mean hospitalization cost of €4,378. Conclusions Parkinson´s disease poses a significant health threat in Spain, particularly in the elderly. While hospitalizations due to Parkinson´s Disease are relatively stable over time, the number of patients presenting with Parkinson´s disease as an important comorbidity has

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. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies.

PubMed

Palma, Jose-Alberto; Kaufmann, Horacio

2018-03-01

Dysfunction of the autonomic nervous system afflicts most patients with Parkinson disease and other synucleinopathies such as dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure, reducing quality of life and increasing mortality. For example, gastrointestinal dysfunction can lead to impaired drug pharmacodynamics causing a worsening in motor symptoms, and neurogenic orthostatic hypotension can cause syncope, falls, and fractures. When recognized, autonomic problems can be treated, sometimes successfully. Discontinuation of potentially causative/aggravating drugs, patient education, and nonpharmacological approaches are useful and should be tried first. Pathophysiology-based pharmacological treatments that have shown efficacy in controlled trials of patients with synucleinopathies have been approved in many countries and are key to an effective management. Here, we review the treatment of autonomic dysfunction in patients with Parkinson disease and other synucleinopathies, summarize the nonpharmacological and current pharmacological therapeutic strategies including recently approved drugs, and provide practical advice and management algorithms for clinicians, with focus on neurogenic orthostatic hypotension, supine hypertension, dysphagia, sialorrhea, gastroparesis, constipation, neurogenic overactive bladder, underactive bladder, and sexual dysfunction. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Exploring the Association Between Rosacea and Parkinson Disease: A Danish Nationwide Cohort Study.

PubMed

Egeberg, Alexander; Hansen, Peter Riis; Gislason, Gunnar H; Thyssen, Jacob P

2016-05-01

The pathogenesis of rosacea is unclear, but increased matrix metalloproteinase target tissue activity appears to play an important role. Parkinson disease and other neurodegenerative disorders also display increased matrix metalloproteinase activity that contribute to neuronal loss. To investigate the risk of incident (new-onset) Parkinson disease in patients with rosacea. A nationwide cohort study of the Danish population was conducted using individual-level linkage of administrative registers. All Danish citizens 18 years or older from January 1, 1997, to December 31, 2011 (N = 5 472 745), were included. Data analysis was conducted from June 26 to July 27, 2015. The main outcome was a diagnosis of Parkinson disease. Incidence rates (IRs) per 10 000 person-years were calculated, and incidence rate ratios (IRRs) adjusted for age, sex, socioeconomic status, smoking, alcohol abuse, medication, and comorbidity were estimated by Poisson regression models. A total of 5 404 692 individuals were included in the reference population; of these, 22 387 individuals (9812 [43.8%] women; mean [SD] age at diagnosis, 75.9 [10.2] years) received a diagnosis of Parkinson disease during the study period and 68 053 individuals (45 712 [67.2%] women; mean age, 42.2 [16.5] years) were registered as having rosacea. The IRs of Parkinson disease per 10 000 person-years were 3.54 (95% CI, 3.49-3.59) in the reference population and 7.62 (95% CI, 6.78-8.57) in patients with rosacea. The adjusted IRR of Parkinson disease was 1.71 (95%, CI 1.52-1.92) in patients with rosacea compared with the reference population. There was a 2-fold increased risk of Parkinson disease in patients classified as having ocular rosacea (adjusted IRR, 2.03 [95% CI, 1.67-2.48]), and tetracycline therapy appeared to reduce the risk of Parkinson disease (adjusted IRR, 0.98 [95% CI, 0.97-0.99]). Rosacea constitutes an independent risk factor for Parkinson disease. This association could be due to shared

Sensorimotor rhythm neurofeedback as adjunct therapy for Parkinson's disease.

PubMed

Philippens, Ingrid H C H M; Wubben, Jacqueline A; Vanwersch, Raymond A P; Estevao, Dave L; Tass, Peter A

2017-08-01

Neurofeedback may enhance compensatory brain mechanisms. EEG-based sensorimotor rhythm neurofeedback training was suggested to be beneficial in Parkinson's disease. In a placebo-controlled study in parkinsonian nonhuman primates we here show that sensorimotor rhythm neurofeedback training reduces MPTP-induced parkinsonian symptoms and both ON and OFF scores during classical L-DOPA treatment. Our findings encourage further development of sensorimotor rhythm neurofeedback training as adjunct therapy for Parkinson's disease which might help reduce L-DOPA-induced side effects.

Parallel appearance of compulsive behaviors and artistic creativity in Parkinson's disease.

PubMed

Joutsa, Juho; Martikainen, Kirsti; Kaasinen, Valtteri

2012-01-01

A 55-year-old male with idiopathic Parkinson's disease developed three behavioral changes under combination therapy with selegiline, cabergoline and levodopa. Co-existent behaviors included severe pathological gambling, punding and novel skills in writing poetry (published poetry books). Brain [(18)F]fluorodopa PET imaging showed decreased tracer uptake in the striatum contralateral to the predominant motor symptoms, consistent with the clinical diagnosis of Parkinson's disease. Uptake in the ventral striatum was markedly high. Brain MRI before and after behavioral changes showed no pathological findings. The patient was diagnosed as having Parkinson's disease together with DSM-IV criteria-fulfilling pathological gambling and punding-like stereotyped behavior. There are no established criteria for the classification of emerged artistic creativity, although there are descriptions of the phenomenon in the literature. Inspired by the case, we conducted a preliminary survey - including 290 patients with Parkinson's disease - exploring the possible relationship between creativity and impulsive-compulsive behaviors. The case, supported by the results of the survey, adds to the cumulative evidence of the association between dopaminergic medication and enhanced creativity, and suggests a possible linkage between increased artistic creativity and impulsive-compulsive behaviors in Parkinson's disease. Furthermore, it could be speculated that the high mesolimbic dopamine function might relate to the behavioral changes observed in this patient, and is suggestive of the overlapping neurobiological mechanisms of compulsive behaviors and artistic creativity.

Parallel Appearance of Compulsive Behaviors and Artistic Creativity in Parkinson's Disease

PubMed Central

Joutsa, Juho; Martikainen, Kirsti; Kaasinen, Valtteri

2012-01-01

A 55-year-old male with idiopathic Parkinson's disease developed three behavioral changes under combination therapy with selegiline, cabergoline and levodopa. Co-existent behaviors included severe pathological gambling, punding and novel skills in writing poetry (published poetry books). Brain [18F]fluorodopa PET imaging showed decreased tracer uptake in the striatum contralateral to the predominant motor symptoms, consistent with the clinical diagnosis of Parkinson's disease. Uptake in the ventral striatum was markedly high. Brain MRI before and after behavioral changes showed no pathological findings. The patient was diagnosed as having Parkinson's disease together with DSM-IV criteria-fulfilling pathological gambling and punding-like stereotyped behavior. There are no established criteria for the classification of emerged artistic creativity, although there are descriptions of the phenomenon in the literature. Inspired by the case, we conducted a preliminary survey – including 290 patients with Parkinson's disease – exploring the possible relationship between creativity and impulsive-compulsive behaviors. The case, supported by the results of the survey, adds to the cumulative evidence of the association between dopaminergic medication and enhanced creativity, and suggests a possible linkage between increased artistic creativity and impulsive-compulsive behaviors in Parkinson's disease. Furthermore, it could be speculated that the high mesolimbic dopamine function might relate to the behavioral changes observed in this patient, and is suggestive of the overlapping neurobiological mechanisms of compulsive behaviors and artistic creativity. PMID:22679432

[Update rehabilitation therapy for Parkinson disease].

PubMed

Hayashi, Akito

2013-01-01

Rehabilitation is essential for treatment of Parkinson's disease. New rehabilitation therapy is updated, in addition to evidence shown with "Parkinson's disease treatment guidelines 2011". Furthermore, a portable gait rhythmogram (acceleration sensor) is presented (not publication). Parkinsonian gait was significantly slow and the steps were small, but the cadence was not different compared as that of normal control. The strength of parkinsonian gait was apparently week compared as normal control. We also could examine consecutive changes of gait rhythm and detect freezing gait in patients. In this study, we could extract the characteristic of the parkinsonian gait and evaluate especially freeing events more objectively. This method may bring us to evaluate severity of parkinsonian gait not only in a consulting room but also daily profile even not to see directly, using the portable gait rhythmogram.

Personality, dopamine, and Parkinson's disease: Insights from subthalamic stimulation.

PubMed

Lhommée, Eugénie; Boyer, François; Wack, Maxime; Pélissier, Pierre; Klinger, Hélène; Schmitt, Emmanuelle; Bichon, Amélie; Fraix, Valérie; Chabardès, Stéphan; Mertens, Patrick; Castrioto, Anna; Kistner, Andrea; Broussolle, Emmanuel; Thobois, Stéphane; Krack, Paul

2017-08-01

Subthalamic stimulation improves the motor and neuropsychiatric symptoms of Parkinson's disease. However, the impact of this treatment on impulse control and personality is the subject of heavy debate. The objective of this study was to investigate personality changes after subthalamic stimulation. Using Cloninger's biosocial model, we assessed personality in 73 Parkinson's disease patients before and 12 months after subthalamic stimulation accompanied by a drastic reduction in dopaminergic medication. Changes in psychobehavioral symptoms were measured using a battery of validated clinical scales (apathy, depression, anxiety, hyperemotionality, mania, psychosis, punding, and impulse control behaviors). One year after surgery, the harm avoidance personality domain total score increased compared with the baseline (+2.8; 34 patients; P < 0.001), as did 3 of its 4 subdomains: anticipatory worry (+0.7; 10 patients; P = 0.005), shyness (+0.6; 7 patients; P = 0.03), and fatigability (+1.1; 10 patients; P = 0.0014). Evolution of the shyness personality trait correlated with the decrease in dopaminergic medication. Total scores in the other personality domains remained unchanged, except for extravagance, a subdomain of novelty seeking, and persistence, a subdomain of reward dependence, which both decreased following surgery (-0.3; 7 patients; and -0.6; 9 patients; P = 0.03 and P = 0.0019, respectively). Although apathy increased, other psychobehavioral symptoms, including impulse control behaviors and neuropsychiatric nonmotor fluctuations, improved. Depression and anhedonia remained stable. Scores in hypodopaminergia and neuropsychiatric nonmotor OFF correlated with harm avoidance. Scores in hyperdopaminergia and neuropsychiatric nonmotor ON correlated with novelty seeking. When subthalamic stimulation is applied in Parkinson's disease, significant changes in personality traits are observed, which may be related to postoperative tapering of

FMR1 Gene Expansion and Scans without Evidence of Dopaminergic Deficits in Parkinsonism Patients

PubMed Central

Hall, DA; Jennings, D; Seibyl, J; Tassone, F; Marek, K

2010-01-01

Purpose To determine if patients with parkinsonism and fragile X mental retardation 1 (FMR1) gene expansions have a striatal dopamine deficit similar to Parkinson disease (PD) patients. Scope The authors studied three patients with parkinsonism carrying small expansions in the FMR1 gene (41–60 CGG) with [123I] -CIT SPECT imaging. The patients responded to dopaminergic medications, but had preserved dopamine transporter density. Conclusions These results suggest that parkinsonism associated with smaller FMR1 expansions may be related to mechanisms other than presynaptic dopaminergic changes and may represent a potential explanation for at least some parkinsonian cases with scans without evidence of dopaminergic deficits (SWEDD). PMID:20702130

Parkinsonism in fragile X-associated tremor/ataxia syndrome (FXTAS): revisited.

PubMed

Niu, Yu-Qiong; Yang, Jin-Chen; Hall, Deborah A; Leehey, Maureen A; Tassone, Flora; Olichney, John M; Hagerman, Randi J; Zhang, Lin

2014-04-01

Parkinsonian features have been used as a minor diagnostic criterion for fragile X-associated tremor/ataxia syndrome (FXTAS). However, prior studies have examined parkinsonism (defined as having bradykinesia with at least rest tremor or postural instability) mostly in premutation carriers without a diagnosis of FXTAS. The current study was intended to elaborate this important aspect of the FXTAS spectrum, and to quantify the relationships between parkinsonism, FXTAS clinical staging and genetic/molecular measures. Thirty eight (38) FXTAS patients and 10 age-matched normal controls underwent a detailed neurological examination that included all but one item (i.e. rigidity) of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS). The FXTAS patient group displayed substantially higher prevalence of parkinsonian features including body bradykinesia (57%) and rest tremor (26%), compared to the control group. Furthermore, parkinsonism was identified in 29% of FXTAS patients. Across all patients, body bradykinesia scores significantly correlated with FXTAS clinical stage, FMR1 mRNA level, and ataxic gait of cerebellar origin, while postural instability was associated with intention tremor. Parkinsonian features in FXTAS appear to be characterized as bradykinesia concurrent with cerebellar gait ataxia, postural instability accompanied by intention tremor, and frequent rest tremor, representing distinctive patterns that highlight the need for further clinical studies including genetic testing for the FMR1 premutation. The association between FMR1 mRNA level and bradykinesia implicates pathophysiological mechanisms which may link FMR1 mRNA toxicity, dopamine deficiency and parkinsonism in FXTAS. Copyright © 2014 Elsevier Ltd. All rights reserved.

Medical and surgical management of advanced Parkinson's disease.

PubMed

Antonini, Angelo; Moro, Elena; Godeiro, Clecio; Reichmann, Heinz

2018-03-23

Advanced Parkinson's disease is characterized by the presence of motor fluctuations, various degree of dyskinesia, and disability with functional impact on activities of daily living and independence. Therapeutic management aims to extend levodopa benefit while minimizing motor complications and includes, in selected cases, the implementation of drug infusion and surgical techniques. In milder forms of motor complications, these can often be controlled with manipulation of levodopa dose and the introduction of supplemental therapies such as catechol-O-methyl transferase inhibitors, monoamine oxidase B inhibitors, and dopamine agonists including apomorphine. Clinical experience and evidence from published studies indicate that when these agents cannot satisfactorily control motor complications, patients should be assessed and considered for device-aided therapies. This review article summarizes some of the newer available therapeutic opportunities such as use of enzyme inhibitors like opicapone and safinamide, adenosine A 2A receptor antagonists, apomorphine and levodopa/carbidopa intestinal gel infusion, deep brain stimulation including the role of closed-loop and adaptive stimulation, and MRI-guided focused ultrasound. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Postural set for balance control is normal in Alzheimer's but not in Parkinson's disease.

PubMed

Chong, R K; Jones, C L; Horak, F B

1999-03-01

It has been suggested that patients with dementia of the Alzheimer type have abnormalities in the basal ganglia, and thus, may have similar sensorimotor problems as patients with basal ganglia degeneration from Parkinson's disease. Whether the similarity extends to balance control is unknown. One distinguishing feature of balance disorder in Parkinson's disease is difficulty with changing postural set in terms of adapting the amplitude of leg muscle activity as a function of support condition. We, therefore, tested whether patients with Alzheimer's disease without extrapyramidal signs would show a similar problem in changing postural set as patients with Parkinson's disease. The ability to quickly change postural set was measured by comparing leg muscle activity under two conditions of support (free stance, versus grasping a frame, or sitting) during backward surface translations, during toes up surface rotations, and during voluntary rise to toes. Results were compared among 12 healthy adults, 8 nondemented Parkinson's patients on their usual dose of medication, and 11 Alzheimer patients without extrapyramidal signs. Subjects with Alzheimer's, but not Parkinson's, disease performed similarly to the healthy control subjects. They changed postural set immediately, by suppressing leg muscle activity to low levels when supported. Parkinson subjects did not change postural set immediately. They did not suppress the tibialis anterior in voluntary rise to toes when holding, nor the soleus in perturbed sitting as much as the healthy control and Alzheimer subjects in the first trial. Instead, the Parkinson subjects changed set more slowly, over repeated and consecutive trials in both protocols. The onset latencies of soleus responses to backward surface translations and perturbed sitting, as well as tibialis anterior responses to toes up rotations, were the same for all three groups. Alzheimer patients without extrapyramidal signs, unlike nondemented Parkinson's disease

Visual hallucinations in Parkinson's disease: a review and phenomenological survey

PubMed Central

Barnes, J; David, A

2001-01-01

OBJECTIVES—Between 8% and 40% of patients with Parkinson's disease undergoing long term treatment will have visual hallucinations during the course of their illness. There were two main objectives: firstly, to review the literature on Parkinson's disease and summarise those factors most often associated with hallucinations; secondly, to carry out a clinical comparison of ambulant patients with Parkinson's disease with and without visual hallucinations, and provide a detailed phenomenological analysis of the hallucinations.
METHODS—A systematic literature search using standard electronic databases of published surveys and case-control studies was undertaken. In parallel, a two stage questionnaire survey was carried out based on members of a local branch of the Parkinson's Disease Society and followed up with a clinical interview.
RESULTS—The review disclosed common factors associated with visual hallucinations in Parkinson's disease including greater age and duration of illness, cognitive impairment, and depression and sleep disturbances. The survey comprised 21 patients with visual hallucinations and 23 without. The hallucinators had a longer duration and a greater severity of illness, and tended to show more depressed mood and cognitive impairment. The typical visual hallucination in these patients is a complex visual image experienced while they are alert and have their eyes open. The image appears without any known trigger or voluntary effort, is somewhat blurred, and commonly moves. It stays present for a period of "seconds" or "minutes". The content can be variable within and between hallucinators, and includes such entities as people, animals, buildings, or scenery. These features resemble those highlighted in hallucinations in the visually impaired (Charles Bonnet's syndrome).
CONCLUSION—A consistent set of factors are associated with visual hallucinations in Parkinson's disease. The results of the phenomenological survey and those of visual

Parkinson's disease candidate gene prioritization based on expression profile of midbrain dopaminergic neurons

PubMed Central

2010-01-01

Background Parkinson's disease is the second most common neurodegenerative disorder. The pathological hallmark of the disease is degeneration of midbrain dopaminergic neurons. Genetic association studies have linked 13 human chromosomal loci to Parkinson's disease. Identification of gene(s), as part of the etiology of Parkinson's disease, within the large number of genes residing in these loci can be achieved through several approaches, including screening methods, and considering appropriate criteria. Since several of the indentified Parkinson's disease genes are expressed in substantia nigra pars compact of the midbrain, expression within the neurons of this area could be a suitable criterion to limit the number of candidates and identify PD genes. Methods In this work we have used the combination of findings from six rodent transcriptome analysis studies on the gene expression profile of midbrain dopaminergic neurons and the PARK loci in OMIM (Online Mendelian Inheritance in Man) database, to identify new candidate genes for Parkinson's disease. Results Merging the two datasets, we identified 20 genes within PARK loci, 7 of which are located in an orphan Parkinson's disease locus and one, which had been identified as a disease gene. In addition to identifying a set of candidates for further genetic association studies, these results show that the criteria of expression in midbrain dopaminergic neurons may be used to narrow down the number of genes in PARK loci for such studies. PMID:20716345

Optimizing care of residents with Parkinsonism in supervised facilities.

PubMed

Makoutonina, Margarita; Iansek, Robert; Simpson, Pam

2010-06-01

People with Parkinsonism (PWP) in residential facilities are usually elderly, cognitively impaired, physically disabled with poor quality of life and a high mortality rate. This paper aims to determine if the care of PWP in residential facilities could be improved by addressing staff knowledge on Parkinson related issues. A curriculum based on the Victorian Comprehensive Parkinson Program (VCPP) was developed and delivered to 118 staff members in 9 facilities across Melbourne. Measures of staff knowledge were undertaken at baseline, 1, 3 and 12 months. Data from a total of 49 residents were used in the analysis. Measures were taken at baseline, 1, 3 and 12 months included dementia screen (MMSE), geriatric depression scale (GDS), quality of life (PDQ39), fatigue (PDFS16), monthly falls diary, Unified Parkinson Disease Rating Scale (I,II,III) Hoehn & Yahr scale (H&Y) and resident/family questionnaire (RFQ) which focused on quality of care provision. It was found that the staff knowledge assessment scores (max = 37) significantly improved post education (P < 0.01) from baseline mean (11.1) and were maintained to 12 months mean (29.0). The residents group improved significantly for all measures at 1 month and these improvements were maintained up to 12 months (except for UPDRS III). This study demonstrated how a simple intervention, resulting in improved staff knowledge, produced a significant and clinically meaningful improvement in the care of PWP.

α-Synuclein oligomers and clinical implications for Parkinson disease

PubMed Central

Kalia, Lorraine V.; Kalia, Suneil K.; McLean, Pamela J.; Lozano, Andres M.; Lang, Anthony E.

2012-01-01

Protein aggregation within the central nervous system has been recognized as a defining feature of neurodegenerative diseases since the early 20th century. Since that time, there has been a growing list of neurodegenerative disorders, including Parkinson disease, which are characterized by inclusions of specific pathogenic proteins. This has led to the long-held dogma that these characteristic protein inclusions, which are composed of large insoluble fibrillar protein aggregates and visible by light microscopy, are responsible for cell death in these diseases. However, the correlation between protein inclusion formation and cytotoxicity is inconsistent suggesting another form of the pathogenic proteins may be contributing to neurodegeneration. There is emerging evidence implicating soluble oligomers, smaller protein aggregates not detectable by conventional microscopy, as potential culprits in the pathogenesis of neurodegenerative diseases. The protein α-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites. However, α-synuclein also forms oligomeric species with certain conformations being toxic to cells. The mechanisms by which these α-synuclein oligomers cause cell death are being actively investigated as they may provide new strategies for diagnosis and treatment of Parkinson disease and related disorders. Here we review the possible role of α-synuclein oligomers in cell death in Parkinson disease and discuss the potential clinical implications. PMID:23225525

A 5-Year Follow-up Study on the Relationship between Obstructive Sleep Apnea and Parkinson Disease.

PubMed

Sheu, Jau-Jiuan; Lee, Hsin-Chien; Lin, Herng-Ching; Kao, Li-Ting; Chung, Shiu-Dong

2015-12-15

Sleep disturbances are among the most common nonmotor symptoms of Parkinson disease. However, no large epidemiological data regarding the association between obstructive sleep apnea (OSA) and Parkinson disease have been reported. The goal of this study was to investigate the risk for Parkinson disease during a 5-y follow-up period after a diagnosis of OSA using a population-based dataset. The data for this retrospective longitudinal cohort study were retrieved from the Taiwan Longitudinal Health Insurance Database 2000. We identified 1,532 patients with OSA as the study cohort and randomly selected 7,660 patients as the comparison cohort. Each subject was individually followed up for a 5-y period to identify those in whom Parkinson disease subsequently developed. Stratified Cox proportional hazard regressions were performed as a means of comparing the 5-y risk of subsequent Parkinson disease between the study cohort and comparison cohort. Of the 9,192 total patients, Parkinson disease developed in 0.73% during the 5-y follow-up period: 1.24% and 0.63% in the OSA and control cohorts, respectively. After censoring patients who died during the follow-up period and adjusting for socio-demographic characteristics, the hazard ratio (HR) of Parkinson disease during the 5-y follow-up period for patients with OSA was 2.26 (95% confidence interval [CI] = 1.32-3.88) compared with comparison patients. In addition, among females, the adjusted HR of Parkinson disease was 3.54 (95% CI = 1.50-8.34) for patients with OSA compared to patients without OSA. However, among males, there was no significantly increased hazard of Parkinson disease for patients with OSA compared to those without OSA. Female patients with OSA were found to be at a significant risk of subsequent Parkinson disease during a 5-y follow-up period. © 2015 American Academy of Sleep Medicine.

Effects of therapy for dysphagia in Parkinson's disease: systematic review.

PubMed

Baijens, Laura W J; Speyer, Renée

2009-03-01

This systematic review explores the effects of dysphagia treatment for Parkinson's disease. The review includes rehabilitative, surgical, pharmacologic, and other treatments. Only oropharyngeal dysphagia is selected for this literature search, excluding dysphagia due to esophageal or gastric disorders. The effects of deep brain stimulation on dysphagia are not included. In general, the literature concerning dysphagia treatment in Parkinson's disease is rather limited. Most effect studies show diverse methodologic problems. Multiple case studies and trials are identified by searching biomedical literature databases PubMed and Embase, and by hand-searching reference lists. The conclusions of most studies cannot be compared with one another because of heterogeneous therapy methods and outcome measures. Further research based on randomized controlled trials to determine the effectiveness of different therapies for dysphagia in Parkinson's disease is required.

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. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

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

Differences in early speech patterns between Parkinson variant of multiple system atrophy and Parkinson's disease.

PubMed

Huh, Young Eun; Park, Jongkyu; Suh, Mee Kyung; Lee, Sang Eun; Kim, Jumin; Jeong, Yuri; Kim, Hee-Tae; Cho, Jin Whan

2015-08-01

In Parkinson variant of multiple system atrophy (MSA-P), patterns of early speech impairment and their distinguishing features from Parkinson's disease (PD) require further exploration. Here, we compared speech data among patients with early-stage MSA-P, PD, and healthy subjects using quantitative acoustic and perceptual analyses. Variables were analyzed for men and women in view of gender-specific features of speech. Acoustic analysis revealed that male patients with MSA-P exhibited more profound speech abnormalities than those with PD, regarding increased voice pitch, prolonged pause time, and reduced speech rate. This might be due to widespread pathology of MSA-P in nigrostriatal or extra-striatal structures related to speech production. Although several perceptual measures were mildly impaired in MSA-P and PD patients, none of these parameters showed a significant difference between patient groups. Detailed speech analysis using acoustic measures may help distinguish between MSA-P and PD early in the disease process. Copyright © 2015 Elsevier Inc. All rights reserved.

Cerebral Microbleeds in Patients with Dementia with Lewy Bodies and Parkinson Disease Dementia.

PubMed

Kim, S W; Chung, S J; Oh, Y-S; Yoon, J H; Sunwoo, M K; Hong, J Y; Kim, J-S; Lee, P H

2015-09-01

The burden of amyloid β is greater in patients with dementia with Lewy bodies than in those with Parkinson disease dementia, and an increased amyloid β load is closely related to a higher incidence of cerebral microbleeds. Here, we investigated the prevalence and topography of cerebral microbleeds in patients with dementia with Lewy bodies and those with Parkinson disease dementia to examine whether cerebral microbleeds are more prevalent in patients with dementia with Lewy bodies than in those with Parkinson disease dementia. The study population consisted of 42 patients with dementia with Lewy bodies, 88 patients with Parkinson disease dementia, and 35 controls who underwent brain MR imaging with gradient recalled-echo. Cerebral microbleeds were classified as deep, lobar, or infratentorial. The frequency of cerebral microbleeds was significantly greater in patients with dementia with Lewy bodies (45.2%) than in those with Parkinson disease dementia (26.1%) or in healthy controls (17.1%; P = .017). Lobar cerebral microbleeds were observed more frequently in the dementia with Lewy bodies group (40.5%) than in the Parkinson disease dementia (17%; P = .004) or healthy control (8.6%; P = .001) group, whereas the frequencies of deep and infratentorial cerebral microbleeds did not differ among the 3 groups. Logistic regression analyses revealed that, compared with the healthy control group, the dementia with Lewy bodies group was significantly associated with the presence of lobar cerebral microbleeds after adjusting for age, sex, nonlobar cerebral microbleeds, white matter hyperintensities, and other vascular risk factors (odds ratio, 4.39 [95% CI, 1.27-15.25]). However, compared with the healthy control group, the Parkinson disease dementia group was not significantly associated with lobar cerebral microbleeds. This study showed that patients with dementia with Lewy bodies had a greater burden of cerebral microbleeds and exhibited a lobar predominance of cerebral

Using a smartphone-based self-management platform to support medication adherence and clinical consultation in Parkinson's disease.

PubMed

Lakshminarayana, Rashmi; Wang, Duolao; Burn, David; Chaudhuri, K Ray; Galtrey, Clare; Guzman, Natalie Valle; Hellman, Bruce; Ben James; Pal, Suvankar; Stamford, Jon; Steiger, Malcolm; Stott, R W; Teo, James; Barker, Roger A; Wang, Emma; Bloem, Bastiaan R; van der Eijk, Martijn; Rochester, Lynn; Williams, Adrian

2017-01-01

The progressive nature of Parkinson's disease, its complex treatment regimens and the high rates of comorbid conditions make self-management and treatment adherence a challenge. Clinicians have limited face-to-face consultation time with Parkinson's disease patients, making it difficult to comprehensively address non-adherence. Here we share the results from a multi-centre (seven centres) randomised controlled trial conducted in England and Scotland to assess the impact of using a smartphone-based Parkinson's tracker app to promote patient self-management, enhance treatment adherence and quality of clinical consultation. Eligible Parkinson's disease patients were randomised using a 1:1 ratio according to a computer-generated random sequence, stratified by centre and using blocks of variable size, to intervention Parkinson's Tracker App or control (Treatment as Usual). Primary outcome was the self-reported score of adherence to treatment (Morisky medication adherence scale -8) at 16 weeks. Secondary outcomes were Quality of Life (Parkinson's disease questionnaire -39), quality of consultation for Parkinson's disease patients ( Patient-centred questionnaire for Parkinson's disease ), impact on non-motor symptoms (Non-motor symptoms questionnaire), depression and anxiety (Hospital anxiety and depression scale) and beliefs about medication (Beliefs about Medication Questionnaire) at 16 weeks. Primary and secondary endpoints were analysed using a generalised linear model with treatment as the fixed effect and baseline measurement as the covariate. 158 patients completed the study (Parkinson's tracker app = 68 and TAU = 90). At 16 weeks Parkinson's tracker app significantly improved adherence, compared to treatment as usual (mean difference: 0.39, 95%CI 0.04-0.74; p  = 0.0304) with no confounding effects of gender, number of comorbidities and age. Among secondary outcomes, Parkinson's tracker app significantly improved patients' perception of quality of

Diagnosis of Parkinson's disease on the basis of clinical and genetic classification: a population-based modelling study.

PubMed

Nalls, Mike A; McLean, Cory Y; Rick, Jacqueline; Eberly, Shirley; Hutten, Samantha J; Gwinn, Katrina; Sutherland, Margaret; Martinez, Maria; Heutink, Peter; Williams, Nigel M; Hardy, John; Gasser, Thomas; Brice, Alexis; Price, T Ryan; Nicolas, Aude; Keller, Margaux F; Molony, Cliona; Gibbs, J Raphael; Chen-Plotkin, Alice; Suh, Eunran; Letson, Christopher; Fiandaca, Massimo S; Mapstone, Mark; Federoff, Howard J; Noyce, Alastair J; Morris, Huw; Van Deerlin, Vivianna M; Weintraub, Daniel; Zabetian, Cyrus; Hernandez, Dena G; Lesage, Suzanne; Mullins, Meghan; Conley, Emily Drabant; Northover, Carrie A M; Frasier, Mark; Marek, Ken; Day-Williams, Aaron G; Stone, David J; Ioannidis, John P A; Singleton, Andrew B

2015-10-01

Accurate diagnosis and early detection of complex diseases, such as Parkinson's disease, has the potential to be of great benefit for researchers and clinical practice. We aimed to create a non-invasive, accurate classification model for the diagnosis of Parkinson's disease, which could serve as a basis for future disease prediction studies in longitudinal cohorts. We developed a model for disease classification using data from the Parkinson's Progression Marker Initiative (PPMI) study for 367 patients with Parkinson's disease and phenotypically typical imaging data and 165 controls without neurological disease. Olfactory function, genetic risk, family history of Parkinson's disease, age, and gender were algorithmically selected by stepwise logistic regression as significant contributors to our classifying model. We then tested the model with data from 825 patients with Parkinson's disease and 261 controls from five independent cohorts with varying recruitment strategies and designs: the Parkinson's Disease Biomarkers Program (PDBP), the Parkinson's Associated Risk Study (PARS), 23andMe, the Longitudinal and Biomarker Study in PD (LABS-PD), and the Morris K Udall Parkinson's Disease Research Center of Excellence cohort (Penn-Udall). Additionally, we used our model to investigate patients who had imaging scans without evidence of dopaminergic deficit (SWEDD). In the population from PPMI, our initial model correctly distinguished patients with Parkinson's disease from controls at an area under the curve (AUC) of 0·923 (95% CI 0·900-0·946) with high sensitivity (0·834, 95% CI 0·711-0·883) and specificity (0·903, 95% CI 0·824-0·946) at its optimum AUC threshold (0·655). All Hosmer-Lemeshow simulations suggested that when parsed into random subgroups, the subgroup data matched that of the overall cohort. External validation showed good classification of Parkinson's disease, with AUCs of 0·894 (95% CI 0·867-0·921) in the PDBP cohort, 0·998 (0·992-1·000

Coding accuracy for Parkinson's disease hospital admissions: implications for healthcare planning in the UK.

PubMed

Muzerengi, S; Rick, C; Begaj, I; Ives, N; Evison, F; Woolley, R L; Clarke, C E

2017-05-01

Hospital Episode Statistics data are used for healthcare planning and hospital reimbursements. Reliability of these data is dependent on the accuracy of individual hospitals reporting Secondary Uses Service (SUS) which includes hospitalisation. The number and coding accuracy for Parkinson's disease hospital admissions at a tertiary centre in Birmingham was assessed. Retrospective, routine-data-based study. A retrospective electronic database search for all Parkinson's disease patients admitted to the tertiary hospital over a 4-year period (2009-2013) was performed on the SUS database using International Classification of Disease codes, and on the local inpatient electronic prescription database, Prescription and Information Communications System, using medication prescriptions. Capture-recapture methods were used to estimate the number of patients and admissions missed by both databases. From the two databases, between July 2009 and June 2013, 1068 patients with Parkinson's disease accounted for 1999 admissions. During these admissions, the Parkinson's disease was coded as a primary or secondary diagnosis. Ninety-one percent of these admissions were recorded on the SUS database. Capture-recapture methods estimated that the number of Parkinson's disease patients admitted during this period was 1127 patients (95% confidence interval: 1107-1146). A supplementary search of both SUS and Prescription and Information Communications System was undertaken using the hospital numbers of these 1068 patients. This identified another 479 admissions. SUS database under-estimated Parkinson's disease admissions by 27% during the study period. The accuracy of disease coding is critical for healthcare policy planning and must be improved. If the under-reporting of Parkinson's disease admissions on the SUS database is repeated nationally, expenditure on Parkinson's disease admissions in England is under-estimated by approximately £61 million per year. Copyright © 2016 The Royal

Cross-cultural adaptation and psychometric evaluations of the Turkish version of Parkinson Fatigue Scale.

PubMed

Ozturk, Erhan Arif; Kocer, Bilge Gonenli; Umay, Ebru; Cakci, Aytul

2018-06-07

The objectives of the present study were to translate and cross-culturally adapt the English version of the Parkinson Fatigue Scale into Turkish, to evaluate its psychometric properties, and to compare them with that of other language versions. A total of 144 patients with idiopathic Parkinson disease were included in the study. The Turkish version of Parkinson Fatigue Scale was evaluated for data quality, scaling assumptions, acceptability, reliability, and validity. The questionnaire response rate was 100% for both test and retest. The percentage of missing data was zero for items, and the percentage of computable scores was full. Floor and ceiling effects were absent. The Parkinson Fatigue Scale provides an acceptable internal consistency (Cronbach's alpha was 0.974 for 1st test and 0.964 for a retest, and corrected item-to-total correlations were ranged from 0.715 to 0.906) and test-retest reliability (Cohen's kappa coefficients were ranged from 0.632 to 0.786 for individuals items, and intraclass correlation coefficient was 0.887 for the overall Parkinson Fatigue Scale Score). An exploratory factor analysis of the items revealed a single factor explaining 71.7% of variance. The goodness-of-fit statistics for the one-factorial confirmatory factor analysis were Tucker Lewis index = 0.961, comparative fit index = 0.971 and root mean square error of approximation = 0.077 for a single factor. The average Parkinson Fatigue Scale Score was correlated significantly with sociodemographic data, clinical characteristics and scores of rating scales. The Turkish version of the Parkinson Fatigue Scale seems to be culturally well adapted and have good psychometric properties. The scale can be used in further studies to assess the fatigue in patients with Parkinson's disease.

Validating the Predicted Effect of Astemizole and Ketoconazole Using a Drosophila Model of Parkinson's Disease.

PubMed

Styczyńska-Soczka, Katarzyna; Zechini, Luigi; Zografos, Lysimachos

2017-04-01

Parkinson's disease is a growing threat to an ever-ageing population. Despite progress in our understanding of the molecular and cellular mechanisms underlying the disease, all therapeutics currently available only act to improve symptoms and do not stop the disease process. It is therefore imperative that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson's. Drug repurposing has been recognized as being equally as promising as de novo drug discovery in the field of neurodegeneration and Parkinson's disease specifically. In this work, we utilize a transgenic Drosophila model of Parkinson's disease, made by expressing human alpha-synuclein in the Drosophila brain, to validate two repurposed compounds: astemizole and ketoconazole. Both have been computationally predicted to have an ameliorative effect on Parkinson's disease, but neither had been tested using an in vivo model of the disease. After treating the flies in parallel, results showed that both drugs rescue the motor phenotype that is developed by the Drosophila model with age, but only ketoconazole treatment reversed the increased dopaminergic neuron death also observed in these models, which is a hallmark of Parkinson's disease. In addition to validating the predicted improvement in Parkinson's disease symptoms for both drugs and revealing the potential neuroprotective activity of ketoconazole, these results highlight the value of Drosophila models of Parkinson's disease as key tools in the context of in vivo drug discovery, drug repurposing, and prioritization of hits, especially when coupled with computational predictions.

Self-management support programs for persons with Parkinson's disease: An integrative review.

PubMed

Kessler, Dorothy; Liddy, Clare

2017-10-01

To identify the characteristics of self-management programs for persons with Parkinson's disease and the evidence for their effectiveness. An integrative literature review was conducted. Studies describing the provision or outcomes of self-management interventions for persons with Parkinson's disease and published in English were included. Two reviewers independently screened and evaluated articles. Interventions were described and compared, and evidence was presented using The Traffic Lighting system. Eighteen interventions were identified, representing a variety of group- and individual-based interventions that differed in structure, components, and outcomes. Notably, 89% were designed specifically for persons with Parkinson's disease and 39% combined self-management support with other therapies. Evidence to support specific self-management programs for persons with Parkinson's disease was limited. However, a moderate quality systematic review and a good quality RCT supported self-management for improving specific domains of quality of life. A variety of interventions have been designed to support self-management by persons with Parkinson's disease. More research is needed to identify key active ingredients and determine which programs are most effective. Self-management programs embedded within rehabilitation are promising. Clinicians should ensure programs include goal setting and problem solving and consider the inclusion of caregivers and peer support. Copyright © 2017 Elsevier B.V. All rights reserved.

Beta-blocker therapy for tremor in Parkinson's disease.

PubMed

Crosby, N J; Deane, K H O; Clarke, C E

2003-01-01

The tremor of Parkinson's disease can cause considerable disability for the individual concerned. Traditional antiparkinsonian therapies such as levodopa have only a minor effect on tremor. Beta-blockers are used to attenuate other forms of tremor such as Essential Tremor or the tremor associated with anxiety. It is thought that beta-blockers may be of use in controlling the tremor of Parkinson's disease. To compare the efficacy and safety of adjuvant beta-blocker therapy against placebo for the treatment of tremor in patients with Parkinson's disease. Electronic searches of MEDLINE, EMBASE, SCISEARCH, BIOSIS, GEROLIT, OLDMEDLINE, LILACS, MedCarib, PASCAL, JICST-EPLUS, RUSSMED, DISSERTATION ABSTRACTS, SIGLE, ISI-ISTP, Aslib Index to Theses, The Cochrane Controlled Trials Register, Clinicaltrials.gov, metaRegister of Controlled Trials, NIDRR, NRR and CENTRAL were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of beta-blockers were contacted. Randomised controlled trials of adjuvant beta-blocker therapy versus placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease. Data was abstracted independently by two of the authors onto standardised forms and disagreements were resolved by discussion. Four randomised controlled trials were found comparing beta-blocker therapy with placebo in patients with idiopathic Parkinson's disease. These were double-blind cross-over studies involving a total of 72 patients. Three studies did not present data from the first arm, instead presenting results as combined data from both treatment arms and both placebo arms. The risk of a carry-over effect into the second arm meant that these results were not analysed. The fourth study presented data from each arm. This was in the form of a mean total score for tremor for each group. Details of the baseline scores, the numbers of patients in each group and standard deviations were not

Association analysis of a polymorphism of the monoamine oxidase B gene with Parkinson`s disease in a Japanese population

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morimoto, Yuji; Murayama, Nobuhiro; Kuwano, Akira

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.more » 7 refs., 2 figs., 1 tab.« less

ABCG2 variant has opposing effects on onset ages of Parkinson's disease and gout

PubMed Central

Matsuo, Hirotaka; Tomiyama, Hiroyuki; Satake, Wataru; Chiba, Toshinori; Onoue, Hiroyuki; Kawamura, Yusuke; Nakayama, Akiyoshi; Shimizu, Seiko; Sakiyama, Masayuki; Funayama, Manabu; Nishioka, Kenya; Shimizu, Toru; Kaida, Kenichi; Kamakura, Keiko; Toda, Tatsushi; Hattori, Nobutaka; Shinomiya, Nariyoshi

2015-01-01

Uric acid (urate) has been suggested to play a protective role in Parkinson's disease onset through its antioxidant activity. Dysfunction of ABCG2, a high-capacity urate exporter, is a major cause for early-onset gout based on hyperuricemia. In this study, the effects of a dysfunctional ABCG2 variant (Q141K, rs2231142) were analyzed on the ages at onset of gout patients (N = 507) and Parkinson's disease patients (N = 1015). The Q141K variant hastened the gout onset (P = 0.0027), but significantly associated with later Parkinson's disease onset (P = 0.025). Our findings will be helpful for development of more effective prevention of Parkinson's disease. PMID:25815357

FMR1 gene expansion and scans without evidence of dopaminergic deficits in parkinsonism patients.

PubMed

Hall, D A; Jennings, D; Seibyl, J; Tassone, F; Marek, K

2010-11-01

To determine if patients with parkinsonism and fragile X mental retardation 1 (FMR1) gene expansions have a striatal dopamine deficit similar to Parkinson disease (PD) patients. The authors studied three patients with parkinsonism carrying small expansions in the FMR1 gene (41-60 CGG) with [(123)I]β-CIT SPECT imaging. The patients responded to dopaminergic medications, but had preserved dopamine transporter density. These results suggest that parkinsonism associated with smaller FMR1 expansions may be related to mechanisms other than pre-synaptic dopaminergic changes and may represent a potential explanation for at least some parkinsonian cases with scans without evidence of dopaminergic deficits (SWEDD). Copyright © 2010 Elsevier Ltd. All rights reserved.

ABCG2 variant has opposing effects on onset ages of Parkinson's disease and gout.

PubMed

Matsuo, Hirotaka; Tomiyama, Hiroyuki; Satake, Wataru; Chiba, Toshinori; Onoue, Hiroyuki; Kawamura, Yusuke; Nakayama, Akiyoshi; Shimizu, Seiko; Sakiyama, Masayuki; Funayama, Manabu; Nishioka, Kenya; Shimizu, Toru; Kaida, Kenichi; Kamakura, Keiko; Toda, Tatsushi; Hattori, Nobutaka; Shinomiya, Nariyoshi

2015-03-01

Uric acid (urate) has been suggested to play a protective role in Parkinson's disease onset through its antioxidant activity. Dysfunction of ABCG2, a high-capacity urate exporter, is a major cause for early-onset gout based on hyperuricemia. In this study, the effects of a dysfunctional ABCG2 variant (Q141K, rs2231142) were analyzed on the ages at onset of gout patients (N = 507) and Parkinson's disease patients (N = 1015). The Q141K variant hastened the gout onset (P = 0.0027), but significantly associated with later Parkinson's disease onset (P = 0.025). Our findings will be helpful for development of more effective prevention of Parkinson's disease.

El uso de la neuromodulación para el tratamiento del temblor

PubMed Central

Bendersky, Damián; Ajler, Pablo; Yampolsky, Claudio

2014-01-01

Introducción: El temblor puede ser un desorden incapacitante y el tratamiento de primera línea para estos pacientes es farmacológico. Sin embargo, este tratamiento puede llevar a una reducción satisfactoria del temblor en sólo el 50% de los pacientes con temblor esencial. La talamotomía era el tratamiento de elección para el temblor refractario al tratamiento médico hasta que comenzó a utilizarse la estimulación cerebral profunda (ECP) del núcleo ventral intermedio (Vim) del tálamo. En la actualidad, raramente se realiza la talamotomía. Métodos: Este artículo es una revisión no sistemática de las indicaciones, resultados, parámetros de programación y técnica quirúrgica de la ECP del Vim para el tratamiento del temblor. Resultados: Aunque los resultados clínicos son similares usando la talamotomía o la ECP del Vim, la primera causa más efectos adversos que la última. Además, la ECP puede ser usada bilateralmente, mientras que la talamotomía tiene un alto riesgo de causar disartria cuando se realiza de ambos lados. La ECP del Vim logró una adecuada mejoría del temblor en varias series de pacientes con temblor causado por temblor esencial, enfermedad de Parkinson o esclerosis múltiple. Además del Vim, hay otros blancos que están siendo usados por varios autores, tales como la zona incerta y las radiaciones prelemniscales. Conclusión: La ECP del Vim es un tratamiento útil para el temblor incapacitante refractario al tratamiento médico. Es esencial realizar una precisa selección de pacientes, así como utilizar una técnica quirúrgica correcta. Aún se desconoce el mejor blanco estereotáctico para el temblor, aunque el Vim es el más usado. PMID:25165613

Dopamine transporter imaging study in parkinsonism occurring in fragile X premutation carriers.

PubMed

Ceravolo, R; Antonini, A; Volterrani, D; Rossi, C; Goldwurm, S; Di Maria, E; Kiferle, L; Bonuccelli, U; Murri, L

2005-12-27

The authors studied four patients with parkinsonism carrying the fragile X premutation using SPECT with ([23)I]FP-CIT. They found evidence of preserved presynaptic nigrostriatal function, suggesting that parkinsonism in the X fragile premutation might be related to postsynaptic dopaminergic changes or different neurotransmitter alterations.

Bone mass and vitamin D levels in Parkinson's disease: is there any difference between genders?

PubMed

Ozturk, Erhan Arif; Gundogdu, Ibrahim; Tonuk, Burak; Kocer, Bilge Gonenli; Tombak, Yasemin; Comoglu, Selcuk; Cakci, Aytul

2016-08-01

[Purpose] The aim of this study was to determine the bone mineral density, vitamin D level, and frequencies of osteopenia and osteoporosis in patients with Parkinson's disease and to compare male and female patients with the controls separately. [Subjects and Methods] One hundred fifteen Parkinson's disease patients (47 males, 68 females; age range: 55-85 years) and 117 age- and gender-matched controls (47 males, 70 females) were enrolled in the study. Bone mineral density measured by dual-energy X-ray absorptiometry and serum D vitamin levels of each participant were recorded. [Results] The mean lumbar spine, femur neck, and total femur bone mineral density levels, T-scores, and vitamin D levels were found to be significantly lower in Parkinson's disease patients in both genders. Furthermore, osteoporosis rates were found be significantly higher only in female Parkinson's disease patients compared with female controls. [Conclusion] Data from the present study revealed that while osteoporosis was significantly higher only in female Parkinson's disease patients, all Parkinson's disease patients had lower bone mineral density scores and vitamin D levels compared with the controls regardless of gender, suggesting that clinicians should pay attention to the osteoporosis risk in Parkinson's disease and that adequate preventive measures should be taken in order to limit the future risk due to osteoporotic fractures.

Cerebello-cortical network fingerprints differ between essential, Parkinson's and mimicked tremors.

PubMed

Muthuraman, Muthuraman; Raethjen, Jan; Koirala, Nabin; Anwar, Abdul Rauf; Mideksa, Kidist G; Elble, Rodger; Groppa, Sergiu; Deuschl, Günter

2018-06-01

Cerebello-thalamo-cortical loops play a major role in the emergence of pathological tremors and voluntary rhythmic movements. It is unclear whether these loops differ anatomically or functionally in different types of tremor. We compared age- and sex-matched groups of patients with Parkinson's disease or essential tremor and healthy controls (n = 34 per group). High-density 256-channel EEG and multi-channel EMG from extensor and flexor muscles of both wrists were recorded simultaneously while extending the hands against gravity with the forearms supported. Tremor was thereby recorded from patients, and voluntarily mimicked tremor was recorded from healthy controls. Tomographic maps of EEG-EMG coherence were constructed using a beamformer algorithm coherent source analysis. The direction and strength of information flow between different coherent sources were estimated using time-resolved partial-directed coherence analyses. Tremor severity and motor performance measures were correlated with connection strengths between coherent sources. The topography of oscillatory coherent sources in the cerebellum differed significantly among the three groups, but the cortical sources in the primary sensorimotor region and premotor cortex were not significantly different. The cerebellar and cortical source combinations matched well with known cerebello-thalamo-cortical connections derived from functional MRI resting state analyses according to the Buckner-atlas. The cerebellar sources for Parkinson's tremor and essential tremor mapped primarily to primary sensorimotor cortex, but the cerebellar source for mimicked tremor mapped primarily to premotor cortex. Time-resolved partial-directed coherence analyses revealed activity flow mainly from cerebellum to sensorimotor cortex in Parkinson's tremor and essential tremor and mainly from cerebral cortex to cerebellum in mimicked tremor. EMG oscillation flowed mainly to the cerebellum in mimicked tremor, but oscillation flowed mainly

Neural response to visual sexual cues in dopamine treatment-linked hypersexuality in Parkinson's disease.

PubMed

Politis, Marios; Loane, Clare; Wu, Kit; O'Sullivan, Sean S; Woodhead, Zoe; Kiferle, Lorenzo; Lawrence, Andrew D; Lees, Andrew J; Piccini, Paola

2013-02-01

Hypersexuality with compulsive sexual behaviour is a significant source of morbidity for patients with Parkinson's disease receiving dopamine replacement therapies. We know relatively little about the pathophysiology of hypersexuality in Parkinson's disease, and it is unknown how visual sexual stimuli, similar to the portrayals of sexuality in the mainstream mass media may affect the brain and behaviour in such susceptible individuals. Here, we have studied a group of 12 patients with Parkinson's disease with hypersexuality using a functional magnetic resonance imaging block design exposing participants to both sexual, other reward-related and neutral visual cues. We hypothesized that exposure to visual sexual cues would trigger increased sexual desire in patients with Parkinson's disease with hypersexuality that would correspond to changes in brain activity in regions linked to dopaminergically stimulated sexual motivation. Patients with Parkinson's disease with hypersexuality were scanned ON and OFF dopamine drugs, and their results were compared with a group of 12 Parkinson's disease control patients without hypersexuality or other impulse control disorders. Exposure to sexual cues significantly increased sexual desire and hedonic responses in the Parkinson's disease hypersexuality group compared with the Parkinson's disease control patients. These behavioural changes corresponded to significant blood oxygen level-dependent signal changes in regions within limbic, paralimbic, temporal, occipital, somatosensory and prefrontal cortices that correspond to emotional, cognitive, autonomic, visual and motivational processes. The functional imaging data showed that the hypersexuality patients' increased sexual desire correlated with enhanced activations in the ventral striatum, and cingulate and orbitofrontal cortices. When the patients with Parkinson's disease with hypersexuality were OFF medication, the functional imaging data showed decreases in activation during

Visuoperceptive region atrophy independent of cognitive status in patients with Parkinson's disease with hallucinations.

PubMed

Goldman, Jennifer G; Stebbins, Glenn T; Dinh, Vy; Bernard, Bryan; Merkitch, Doug; deToledo-Morrell, Leyla; Goetz, Christopher G

2014-03-01

Visual hallucinations are frequent, disabling complications of advanced Parkinson's disease, but their neuroanatomical basis is incompletely understood. Previous structural brain magnetic resonance imaging studies suggest volume loss in the mesial temporal lobe and limbic regions in subjects with Parkinson's disease with visual hallucinations, relative to those without visual hallucinations. However, these studies have not always controlled for the presence of cognitive impairment or dementia, which are common co-morbidities of hallucinations in Parkinson's disease and whose neuroanatomical substrates may involve mesial temporal lobe and limbic regions. Therefore, we used structural magnetic resonance imaging to examine grey matter atrophy patterns associated with visual hallucinations, comparing Parkinson's disease hallucinators to Parkinson's disease non-hallucinators of comparable cognitive function. We studied 50 subjects with Parkinson's disease: 25 classified as current and chronic visual hallucinators and 25 as non-hallucinators, who were matched for cognitive status (demented or non-demented) and age (± 3 years). Subjects underwent (i) clinical evaluations; and (ii) brain MRI scans analysed using whole-brain voxel-based morphometry techniques. Clinically, the Parkinson's disease hallucinators did not differ in their cognitive classification or performance in any of the five assessed cognitive domains, compared with the non-hallucinators. The Parkinson's disease groups also did not differ significantly in age, motor severity, medication use or duration of disease. On imaging analyses, the hallucinators, all of whom experienced visual hallucinations, exhibited grey matter atrophy with significant voxel-wise differences in the cuneus, lingual and fusiform gyri, middle occipital lobe, inferior parietal lobule, and also cingulate, paracentral, and precentral gyri, compared with the non-hallucinators. Grey matter atrophy in the hallucinators occurred

Effects of levodopa on corticostriatal circuits supporting working memory in Parkinson's disease.

PubMed

Simioni, Alison C; Dagher, Alain; Fellows, Lesley K

2017-08-01

Working memory dysfunction is common in Parkinson's disease, even in its early stages, but its neural basis is debated. Working memory performance likely reflects a balance between corticostriatal dysfunction and compensatory mechanisms. We tested this hypothesis by examining working memory performance with a letter n-back task in 19 patients with mild-moderate Parkinson's disease and 20 demographically matched healthy controls. Parkinson's disease patients were tested after an overnight washout of their usual dopamine replacement therapy, and again after a standard dose of levodopa. FMRI was used to assess task-related activation and resting state functional connectivity; changes in BOLD signal were related to performance to disentangle pathological and compensatory processes. Parkinson's disease patients off dopamine replacement therapy displayed significantly reduced spatial extent of task-related activation in left prefrontal and bilateral parietal cortex, and poorer working memory performance, compared to controls. Amongst the Parkinson's disease patients off dopamine replacement therapy, relatively better performance was associated with greater activation of right dorsolateral prefrontal cortex compared to controls, consistent with compensatory right hemisphere recruitment. Administration of levodopa remediated the working memory deficit in the Parkinson's disease group, and resulted in a different pattern of performance-correlated activity, with a shift to greater left ventrolateral prefrontal cortex activation in patients on, compared to off dopamine replacement therapy. Levodopa also significantly increased resting-state functional connectivity between caudate and right parietal cortex (within the right fronto-parietal attentional network). The strength of this connectivity contributed to better performance in patients and controls, suggesting a general compensatory mechanism. These findings argue that Parkinson's disease patients can recruit additional

Pain processing in atypical Parkinsonisms and Parkinson disease: A comparative neurophysiological study.

PubMed

Avenali, Micol; Tassorelli, Cristina; De Icco, Roberto; Perrotta, Armando; Serrao, Mariano; Fresia, Mauro; Pacchetti, Claudio; Sandrini, Giorgio

2017-10-01

Pain is a frequent non-motor feature in Parkinsonism but mechanistic data on the alteration of pain processing are insufficient to understand the possible causes and to define specifically-targeted treatments. we investigated spinal nociception through the neurophysiological measure of the threshold (TR) of nociceptive withdrawal reflex (NWR) and its temporal summation threshold (TST) comparatively in 12 Progressive Supranuclear Palsy (PSP) subjects, 11 Multiple System Atrophy (MSA) patients, 15 Parkinson's disease (PD) subjects and 24 healthy controls (HC). We also investigated the modulatory effect of L-Dopa in these three parkinsonian groups. We found a significant reduction in the TR of NWR and in the TST of NWR in PSP, MSA and PD patients compared with HC. L-Dopa induced an increase in the TR of NWR in the PSP group while TST of NWR increased in both PSP and PD. Our neurophysiological findings identify a facilitation of nociceptive processing in PSP that is broadly similar to that observed in MSA and PD. Specific peculiarities have emerged for PSP. Our data advance the knowledge of the neurophysiology of nociception in the advanced phases of parkinsonian syndromes and on the role of dopaminergic pathways in the control on pain processing. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Cognitive screening in Parkinson's disease: Comparison of the Parkinson Neuropsychometric Dementia Assessment (PANDA) with 3 other short scales.

PubMed

Gasser, A-I; Calabrese, P; Kalbe, E; Kessler, J; Rossier, P

2016-02-01

Cognitive screening is crucial in Parkinson's disease (PD). However, there is still a lack of short tools in French. In this study, we aimed to compare the Parkinson Neuropsychometric Dementia Assessment (PANDA) with the Mini Mental Parkinson (MMP), the Mini Mental State Examination (MMSE) and the Clock Test in French-speaking patients. We also aimed to propose cut-off scores for cognitive impairment and dementia for the French language version of the PANDA. Fifty-one patients with PD took the PANDA, the MMSE, the MMP, and the Clock Test. They also underwent extensive neuropsychological testing by a neuropsychologist who was blinded to the above-mentioned screening test results. Patients were classified as either having normal cognition (n=15), mild cognitive impairment (n=20) or dementia (n=16). When compared with the three other screening tools, the PANDA exhibited the highest area under the curve (AUC) for both cognitive disorders and dementia. Using the cut-off scores proposed for the German version, the PANDA had 94% specificity and 100% sensitivity for dementia and 100% and 72%, respectively for cognitive disorders. In our study, the PANDA exhibited a higher discriminative power than the three other tests in detecting cognitive disorders and dementia. In PD patients, the PANDA should thus be considered for the detection of cognitive impairment in routine clinical practice. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Reversible Pharmacological Induction of Motor Symptoms in MPTP-Treated Mice at the Presymptomatic Stage of Parkinsonism: Potential Use for Early Diagnosis of Parkinson's Disease.

PubMed

Khakimova, Gulnara R; Kozina, Elena A; Kucheryanu, Valerian G; Ugrumov, Michael V

2017-07-01

A crucial event in the pathogenesis of Parkinson's disease is the death of dopaminergic neurons of the nigrostriatal system, which are responsible for the regulation of motor function. Motor symptoms first appear in patients 20-30 years after the onset of the neurodegeneration, when there has been a loss of an essential number of neurons and depletion of compensatory reserves of the brain, which explains the low efficiency of treatment. Therefore, the development of a technology for the diagnosing of Parkinson's disease at the preclinical stage is of a high priority in neurology. In this study, we have developed at an experimental model a fundamentally novel for neurology approach for diagnosis of Parkinson's disease at the preclinical stage. This methodology, widely used for the diagnosis of chronic diseases in the internal medicine, is based on the application of a challenge test that temporarily increases the latent failure of a specific functional system, thereby inducing the short-term appearance of clinical symptoms. The provocation test was developed by a systemic administration of α-methyl-p-tyrosine (αMpT), a reversible inhibitor of tyrosine hydroxylase to MPTP-treated mice at the presymptomatic stage of parkinsonism. For this, we first selected a minimum dose of αMpT, which caused a decrease of the dopamine level in the striatum of normal mice below the threshold at which motor dysfunctions appear. Then, we found the maximum dose of αMpT at which a loss of dopamine in the striatum of normal mice did not reach the threshold level, and motor behavior was not impaired. We showed that αMpT at this dose induced a decrease of the dopamine concentration in the striatum of MPTP-treated mice at the presymptomatic stage of parkinsonism below a threshold level that results in the impairment of motor behavior. Finally, we proved that αMpT exerts a temporal and reversible influence on the nigrostriatal dopaminergic system of MPTP-treated mice with no long

Multidimensional exercise for people with Parkinson's disease: a case report.

PubMed

Kluding, Patricia; McGinnis, Patricia Quinn

2006-06-01

The primary impairments associated with Parkinson's disease occur in combination with the secondary, preventable effects of immobility. A community-based fitness program may help increase activity and maintain function in people in the early or middle stages of the disease. This article describes a unique program designed to reduce fall risk and promote independent exercise for people with Parkinson's disease. Two 66-year-old males, both community ambulators and in early or middle stages of Parkinson's disease, participated in 3 months of various physical activities. Group balance classes were held twice weekly during the first month, participants joined a fitness center and self-directed their exercise program during the second month, and group Tai Chi classes were held twice weekly during the third month. At conclusion of the program, participants were given suggestions for continued physical fitness activities. After the 3-month program, improvements were noted for both individuals in functional reach, Timed Up and Go, and Berg Balance scores. Both participants continued to exercise regularly for at least 8 months following the program. Two individuals with Parkinson's disease demonstrated improvement in their balance test performance over a 3-month period. Perhaps most importantly, these participants independently continued exercising after completing this program.

Elevated Cystatin C Levels Are Associated with Cognitive Impairment and Progression of Parkinson Disease.

PubMed

Hu, Wei-Dong; Chen, Jing; Mao, Cheng-Jie; Feng, Ping; Yang, Ya-Ping; Luo, Wei-Feng; Liu, Chun-Feng

2016-09-01

We investigated the relationship between serum cystatin C (CysC) levels and cognitive dysfunction and disease progression in patients with Parkinson disease. Previous studies have reported altered CysC levels in neurodegenerative disorders, but only a few studies have explored the role of CysC and its relationship to cognitive dysfunction in Parkinson disease. We measured serum levels of CysC, creatinine, urea, and uric acid in 142 patients with Parkinson disease and 146 healthy controls. We assessed disease progression using the Hoehn and Yahr scale, and cognitive function using the Montreal Cognitive Assessment (Beijing version). The patients with Parkinson disease had significantly higher CysC levels than the controls (P<0.001). CysC level correlated significantly with age (r=0.494, P<0.001), sex (r=0.150, P=0.011), and serum creatinine level (r=0.377, P<0.001), but not with levels of urea or uric acid (P>0.05). CysC level was a significant independent predictor of Parkinson disease (odds ratio=23.143, 95% confidence interval: 5.485-97.648, P<0.001) in multivariate logistic regression analysis. In the Parkinson disease group, a higher CysC level was associated with a more advanced Hoehn and Yahr stage (r=0.098, P<0.05) and a lower Montreal Cognitive Assessment score (r=-0.381, P=0.003). Serum CysC levels can predict disease severity and cognitive dysfunction in patients with Parkinson disease. The exact role of CysC remains to be determined.

Changes in kynurenine pathway metabolism in Parkinson patients with L-DOPA-induced dyskinesia.

PubMed

Havelund, Jesper F; Andersen, Andreas D; Binzer, Michael; Blaabjerg, Morten; Heegaard, Niels H H; Stenager, Egon; Faergeman, Nils J; Gramsbergen, Jan Bert

2017-09-01

L-3,4-Dihydroxyphenylalanine (L-DOPA) is the most effective drug in the symptomatic treatment of Parkinson's disease, but chronic use is associated with L-DOPA-induced dyskinesia in more than half the patients after 10 years of treatment. L-DOPA treatment may affect tryptophan metabolism via the kynurenine pathway. Altered levels of kynurenine metabolites can affect glutamatergic transmission and may play a role in the development of L-DOPA-induced dyskinesia. In this study, we assessed kynurenine metabolites in plasma and cerebrospinal fluid of Parkinson's disease patients and controls. Parkinson patients (n = 26) were clinically assessed for severity of motor symptoms (UPDRS) and L-DOPA-induced dyskinesia (UDysRS). Plasma and cerebrospinal fluid samples were collected after overnight fasting and 1-2 h after intake of L-DOPA or other anti-Parkinson medication. Metabolites were analyzed in plasma and cerebrospinal fluid of controls (n = 14), Parkinson patients receiving no L-DOPA (n = 8), patients treated with L-DOPA without dyskinesia (n = 8), and patients with L-DOPA-induced dyskinesia (n = 10) using liquid chromatography-mass spectrometry. We observed approximately fourfold increase in the 3-hydroxykynurenine/kynurenic acid ratio in plasma of Parkinson's patients with L-DOPA-induced dyskinesia. Anthranilic acid levels were decreased in plasma and cerebrospinal fluid of this patient group. 5-Hydroxytryptophan levels were twofold increased in all L-DOPA-treated Parkinson's patients. We conclude that a higher 3-hydroxykynurenine/kynurenic acid ratio in plasma may serve as a biomarker for L-DOPA-induced dyskinesia. Longitudinal studies including larger patients cohorts are needed to verify whether the changes observed here may serve as a prognostic marker for L-DOPA-induced dyskinesia. © 2017 International Society for Neurochemistry.

Mitochondrial dynamics in Parkinson's disease: a role for α-synuclein?

PubMed Central

Pozo Devoto, Victorio M.

2017-01-01

ABSTRACT The distinctive pathological hallmarks of Parkinson's disease are the progressive death of dopaminergic neurons and the intracellular accumulation of Lewy bodies enriched in α-synuclein protein. Several lines of evidence from the study of sporadic, familial and pharmacologically induced forms of human Parkinson's disease also suggest that mitochondrial dysfunction plays an important role in disease progression. Although many functions have been proposed for α-synuclein, emerging data from human and animal models of Parkinson's disease highlight a role for α-synuclein in the control of neuronal mitochondrial dynamics. Here, we review the α-synuclein structural, biophysical and biochemical properties that influence relevant mitochondrial dynamic processes such as fusion-fission, transport and clearance. Drawing on current evidence, we propose that α-synuclein contributes to the mitochondrial defects that are associated with the pathology of this common and progressive neurodegenerative disease. PMID:28883016

Botulinum toxin in parkinsonism: The when, how, and which for botulinum toxin injections.

PubMed

Cardoso, Francisco

2018-06-01

The aim of this article is to provide a review of the use of injections of botulinum toxin in the management of selected symptoms and signs of Parkinson's disease and other forms of parkinsonism. Sialorrhea is defined as inability to control oral secretions, resulting in excessive saliva in the oropharynx. There is a high level of evidence for the treatment of sialorrhea in parkinsonism with injections of different forms of botulinum toxin type A as well as botulinum toxin type B. Tremor can be improved by the use of botulinum toxin injections but improved tremor control often leads to concomitant motor weakness, limiting its use. Levodopa induced dyskinesias are difficult to treat with botulinum toxin injections because of their variable frequency and direction. Apraxia of eyelid opening, a sign more commonly seen in progressive supranuclear palsy and other tauopathies, often improves after botulinum toxin injections. Recent data suggest that regardless of the underlying mechanism, pain in parkinsonism can be alleviated by botulinum toxin injections. Finally, freezing of gait, camptocormia and Pisa syndrome in parkinsonism almost invariably fail to respond to botulinum toxin injections. Copyright © 2017 Elsevier Ltd. All rights reserved.

The neurobiology of glucocerebrosidase-associated parkinsonism: a positron emission tomography study of dopamine synthesis and regional cerebral blood flow.

PubMed

Goker-Alpan, Ozlem; Masdeu, Joseph C; Kohn, Philip D; Ianni, Angela; Lopez, Grisel; Groden, Catherine; Chapman, Molly C; Cropp, Brett; Eisenberg, Daniel P; Maniwang, Emerson D; Davis, Joie; Wiggs, Edythe; Sidransky, Ellen; Berman, Karen F

2012-08-01

Mutations in GBA, the gene encoding glucocerebrosidase, the enzyme deficient in Gaucher disease, are common risk factors for Parkinson disease, as patients with Parkinson disease are over five times more likely to carry GBA mutations than healthy controls. Patients with GBA mutations generally have an earlier onset of Parkinson disease and more cognitive impairment than those without GBA mutations. We investigated whether GBA mutations alter the neurobiology of Parkinson disease, studying brain dopamine synthesis and resting regional cerebral blood flow in 107 subjects (38 women, 69 men). We measured dopamine synthesis with (18)F-fluorodopa positron emission tomography, and resting regional cerebral blood flow with H(2)(15)O positron emission tomography in the wakeful, resting state in four study groups: (i) patients with Parkinson disease and Gaucher disease (n = 7, average age = 56.6 ± 9.2 years); (ii) patients with Parkinson disease without GBA mutations (n = 11, 62.1 ± 7.1 years); (iii) patients with Gaucher disease without parkinsonism, but with a family history of Parkinson disease (n = 14, 52.6 ± 12.4 years); and (iv) healthy GBA-mutation carriers with a family history of Parkinson disease (n = 7, 50.1 ± 18 years). We compared each study group with a matched control group. Data were analysed with region of interest and voxel-based methods. Disease duration and Parkinson disease functional and staging scores were similar in the two groups with parkinsonism, as was striatal dopamine synthesis: both had greatest loss in the caudal striatum (putamen Ki loss: 44 and 42%, respectively), with less reduction in the caudate (20 and 18% loss). However, the group with both Parkinson and Gaucher diseases showed decreased resting regional cerebral blood flow in the lateral parieto-occipital association cortex and precuneus bilaterally. Furthermore, two subjects with Gaucher disease without parkinsonian manifestations showed diminished striatal dopamine. In conclusion

The neurobiology of glucocerebrosidase-associated parkinsonism: a positron emission tomography study of dopamine synthesis and regional cerebral blood flow

PubMed Central

Goker-Alpan, Ozlem; Masdeu, Joseph C.; Kohn, Philip D.; Ianni, Angela; Lopez, Grisel; Groden, Catherine; Chapman, Molly C.; Cropp, Brett; Eisenberg, Daniel P.; Maniwang, Emerson D.; Davis, Joie; Wiggs, Edythe; Berman, Karen F.

2012-01-01

Mutations in GBA, the gene encoding glucocerebrosidase, the enzyme deficient in Gaucher disease, are common risk factors for Parkinson disease, as patients with Parkinson disease are over five times more likely to carry GBA mutations than healthy controls. Patients with GBA mutations generally have an earlier onset of Parkinson disease and more cognitive impairment than those without GBA mutations. We investigated whether GBA mutations alter the neurobiology of Parkinson disease, studying brain dopamine synthesis and resting regional cerebral blood flow in 107 subjects (38 women, 69 men). We measured dopamine synthesis with 18F-fluorodopa positron emission tomography, and resting regional cerebral blood flow with H215O positron emission tomography in the wakeful, resting state in four study groups: (i) patients with Parkinson disease and Gaucher disease (n = 7, average age = 56.6 ± 9.2 years); (ii) patients with Parkinson disease without GBA mutations (n = 11, 62.1 ± 7.1 years); (iii) patients with Gaucher disease without parkinsonism, but with a family history of Parkinson disease (n = 14, 52.6 ± 12.4 years); and (iv) healthy GBA-mutation carriers with a family history of Parkinson disease (n = 7, 50.1 ± 18 years). We compared each study group with a matched control group. Data were analysed with region of interest and voxel-based methods. Disease duration and Parkinson disease functional and staging scores were similar in the two groups with parkinsonism, as was striatal dopamine synthesis: both had greatest loss in the caudal striatum (putamen Ki loss: 44 and 42%, respectively), with less reduction in the caudate (20 and 18% loss). However, the group with both Parkinson and Gaucher diseases showed decreased resting regional cerebral blood flow in the lateral parieto-occipital association cortex and precuneus bilaterally. Furthermore, two subjects with Gaucher disease without parkinsonian manifestations showed diminished striatal dopamine. In conclusion, the

Quality of life in people with Parkinson's disease: the relevance of social relationships and communication.

PubMed

Takahashi, Kayoko; Kamide, Naoto; Suzuki, Makoto; Fukuda, Michinari

2016-01-01

[Purpose] Maintaining high quality of life is crucial for the rehabilitation of patients with Parkinson's disease. The quality of life scales currently in use do not assess all quality of life domains or their importance for each individual. Therefore, a new quality of life measure, the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting, was used to investigate quality of life in people with Parkinson's disease. [Subjects and Methods] Fifteen people with idiopathic Parkinson's disaese (average age = 80.0 years, standard deviation = 10.3 years, Hoehn & Yahr stages 1-4) were interviewed using the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting. Its quality of life constructs were tested by comparing them against disease-specific quality of life (39-items Parkinson's Disease Questionnaire), motor functioning (Unified Parkinson's Disease Rating Scale Part III), and activities of daily living (Barthel Index). [Results] Social connections such as "family" and "friends" were revealed as important constructs of life satisfaction. The Schedule for the Evaluation of Individual Quality of Life-Direct Weighting was not significantly correlated with the 39-items Parkinson's Disease Questionnaire, Unified Parkinson's Disease Rating Scale Part III, or Barthel Index but was significantly correlated with the "communication" dimension of the 39-items Parkinson's Disease Questionnaire. [Conclusion] The Schedule for the Evaluation of Individual Quality of Life-Direct Weighting detected various domains of quality of life, especially social relationships with family and friends. "Being heard" was also revealed as an essential component of life satisfaction, as it provides patients with a feeling of acceptance and assurance, possibly resulting in better quality of life.

ParkinsonNet: A Low-Cost Health Care Innovation With A Systems Approach From The Netherlands.

PubMed

Bloem, Bas R; Rompen, Lonneke; Vries, Nienke M de; Klink, Ab; Munneke, Marten; Jeurissen, Patrick

2017-11-01

ParkinsonNet, a low-cost innovation to optimize care for patients with Parkinson disease, was developed in 2004 as a network of physical therapists in several regions in the Netherlands. Since that time, the network has achieved full national reach, with 70 regional networks and around 3,000 specifically trained professionals from 12 disciplines. Key elements include the empowerment of professionals who are highly trained and specialized in Parkinson disease, the empowerment of patients by education and consultation, and the empowerment of integrated multidisciplinary teams to better address and manage the disease. Studies have found that the ParkinsonNet approach leads to outcomes that are at least as good as, if not better than, outcomes from usual care. One study found a 50 percent reduction in hip fractures and fewer inpatient admissions. Other studies suggest that ParkinsonNet leads to modest but important cost savings (at least US$439 per patient annually). These cost savings outweigh the costs of building and maintaining the network. Because of ParkinsonNet's success, the program has now spread to several other countries and serves as a model of a successful and scalable frugal innovation.

Freezing of gait in Parkinson's disease: from pathophysiology to emerging therapies.

PubMed

Cucca, Alberto; Biagioni, Milton C; Fleisher, Jori E; Agarwal, Shashank; Son, Andre; Kumar, Pawan; Brys, Miroslaw; Di Rocco, Alessandro

2016-10-01

Freezing of gait (FOG) is 'an episodic inability to generate effective stepping in the absence of any known cause other than parkinsonism or high level gait disorders'. FOG is one of the most disabling symptoms in Parkinson's disease, especially in its more advanced stages. Early recognition is important as FOG is related to higher fall risk and poorer prognosis. Although specific treatments are still elusive, there have been recent advances in the development of new therapeutic approaches. The aim of this review is to present the latest knowledge regarding the phenomenology, pathogenesis, diagnostic assessment and conventional treatment of FOG in Parkinson's disease. A review of the evidence supporting noninvasive brain stimulation will follow to highlight the potential of these strategies.

Exercise hemodynamics in Parkinson's disease and autonomic dysfunction.

PubMed

Low, David A; Vichayanrat, Ekawat; Iodice, Valeria; Mathias, Christopher J

2014-05-01

To clarify the characteristics of hemodynamic responses to exercise and orthostasis in Parkinson's disease patients, especially those with autonomic failure. Clinical audit of supine cycling exercise test data (with active standing tests pre- and post-exercise) of Parkinson's patients with autonomic dysfunction. 23 patients (71 ± 7 yr, 7 females) with a confirmed diagnosis of Parkinson's were identified. Group mean systolic blood pressure (SBP) fell during pre-exercise standing (-39 ± 29 mmHg, P < 0.001, 17 patients had orthostatic hypotension (OH)), while heart rate (HR) increased (+13 ± 7 beats min(-1), P < 0.001). SBP (P < 0.001) increased during exercise with a wide variation in responses. SBP increased in 13 patients (INC; +30 ± 14 mmHg) and either did not change or decreased in 10 patients (DEC -12 ± 11 mmHg, P < 0.001 vs INC). The increase in HR was not different between sub-groups (30 ± 12 vs 25 ± 10 beats min(-1), INC vs. DEC, P = 0.29). The size of the pre-exercise stand SBP reduction was greater in DEC vs INC (-64 ± 23 (10 out of 10 had OH) vs -19 ± 16 mmHg (7 out of 13 had OH), respectively, P < 0.001). The HR elevation was not different between sub-groups (13 ± 8 vs 13 ± 4 beats min(-1), DEC vs INC, P = 0.94). Post-exercise SBP/DBP were lower for both sub-groups compared to pre-exercise and the standing SBP reduction post-exercise was not greater relative to pre-exercise in either sub-group. Exercise-induced hypotension can occur in Parkinson's disease patients with autonomic failure with the magnitude of the exercise response being related to the severity of autonomic dysfunction. Exercise does not appear to worsen OH in this sample of Parkinson's patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Improving response inhibition in Parkinson's disease with atomoxetine.

PubMed

Ye, Zheng; Altena, Ellemarije; Nombela, Cristina; Housden, Charlotte R; Maxwell, Helen; Rittman, Timothy; Huddleston, Chelan; Rae, Charlotte L; Regenthal, Ralf; Sahakian, Barbara J; Barker, Roger A; Robbins, Trevor W; Rowe, James B

2015-04-15

Dopaminergic drugs remain the mainstay of Parkinson's disease therapy but often fail to improve cognitive problems such as impulsivity. This may be due to the loss of other neurotransmitters, including noradrenaline, which is linked to impulsivity and response inhibition. We therefore examined the effect of the selective noradrenaline reuptake inhibitor atomoxetine on response inhibition in a stop-signal paradigm. This pharmacological functional magnetic resonance imaging study used a double-blinded randomized crossover design with low-frequency inhibition trials distributed among frequent Go trials. Twenty-one patients received 40 mg atomoxetine or placebo. Control subjects were tested on no-drug. The effects of disease and drug on behavioral performance, regional brain activity, and functional connectivity were analyzed using general linear models. Anatomical connectivity was examined using diffusion-weighted imaging. Patients with Parkinson's disease had longer stop-signal reaction times, less stop-related activation in the right inferior frontal gyrus (RIFG), and weaker functional connectivity between the RIFG and striatum compared with control subjects. Atomoxetine enhanced stop-related RIFG activation in proportion to disease severity. Although there was no overall behavioral benefit from atomoxetine, analyses of individual differences revealed that enhanced response inhibition by atomoxetine was associated with increased RIFG activation and functional frontostriatal connectivity. Improved performance was more likely in patients with higher structural frontostriatal connectivity. This study suggests that enhanced prefrontal cortical activation and frontostriatal connectivity by atomoxetine may improve response inhibition in Parkinson's disease. These results point the way to new stratified clinical trials of atomoxetine to treat impulsivity in selected patients with Parkinson's disease. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

S4. ASYMMETRIC DRUG-INDUCED PARKINSONISM IS RELATED TO PSYCHOPATHOLOGY

PubMed Central

Pieters, Lydia; Bakker, P Roberto; Van Harten, Peter N

2018-01-01

Abstract Background Drug-Induced Parkinsonism (DIP) is the most common movement disorder induced by antipsychotics. The prevalence of DIP in chronic psychiatric populations ranges between 17 and 72% (1–3). Although, DIP is mostly symmetric, asymmetric DIP is reported in 18 to 54% of the patients. (4). There are no studies to the clinical relevance of asymmetric DIP. We investigated the prevalence of motor asymmetry in DIP and its relationship to the severity of psychopathology in a prospective study. Methods In a cohort study of 207 long-stay psychiatric inpatients the prevalence of DIP was assessed at least two times (mean follow-up 1.1 year) in each patient (5). DIP was assessed with the Unified Parkinson Disease Rating Scale (UPDRS) and the prevalence of persistent DIP was 56.2%. Patients with at least one time parkinsonism in the upper/lower limb(s) were included for analyses. Asymmetry of parkinsonism was calculated with the symmetry index (Figure 1). A cut-off value of ≥ 0,20 was used for the definition of asymmetric DIP. Multilevel mixed models were built to explore the relationship between asymmetry in DIP and the severity of psychopathology, measured on the Clinical Global Impression-Schizophrenia scale severity index (CGI-SCH SI). Results In a cohort study of 207 long-stay psychiatric inpatients the prevalence of DIP was assessed at least two times (mean follow-up 1.1 year) in each patient (5). DIP was assessed with the Unified Parkinson Disease Rating Scale (UPDRS) and the prevalence of persistent DIP was 56.2%. Patients with at least one time parkinsonism in the upper/lower limb(s) were included for analyses. Asymmetry of parkinsonism was calculated with the symmetry index (Figure 1). A cut-off value of ≥ 0,20 was used for the definition of asymmetric DIP. Multilevel mixed models were built to explore the relationship between asymmetry in DIP and the severity of psychopathology, measured on the Clinical Global Impression-Schizophrenia scale

Rumination and behavioural factors in Parkinson's disease depression.

PubMed

Julien, Camille L; Rimes, Katharine A; Brown, Richard G

2016-03-01

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. 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. 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. 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. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Rasagiline: a review of its use in the treatment of idiopathic Parkinson's disease.

PubMed

Hoy, Sheridan M; Keating, Gillian M

2012-03-26

Rasagiline (Azilect®), a selective, irreversible, monoamine oxidase-B inhibitor, is available in the EU, the US and in several other countries worldwide, including Canada and Israel. It is indicated for the treatment of idiopathic Parkinson's disease as monotherapy or as adjunctive therapy to levodopa in patients [corrected]with end-of-dose fluctuations in the EU and for the treatment of adult patients with the signs and symptoms of idiopathic Parkinson's disease in the US. This article reviews the pharmacological properties, therapeutic efficacy and tolerability of rasagiline as monotherapy or as adjunctive therapy to levodopa in patients with Parkinson's disease. Oral rasagiline as monotherapy or as adjunctive therapy to levodopa was effective in the symptomatic treatment of adult patients with Parkinson's disease participating in double-blind, placebo-controlled, multinational studies. In patients with early Parkinson's disease, monotherapy with rasagiline 1 mg/day (recommended dosage) significantly slowed the rate of worsening (i.e. an increase in the Unified Parkinson's Disease Rating Scale [UPDRS] score) in the ADAGIO and TEMPO studies, with the results from the ADAGIO study for rasagiline 1 mg/day suggesting a slowing of clinical progression. However, at the higher dosage of 2 mg/day, rasagiline met the primary endpoint in the TEMPO study and the first, but not the second, of three hierarchical primary endpoints in the ADAGIO study. Compared with delayed-start rasagiline monotherapy, early initiation was associated with a slower long-term progression of the clinical signs and symptoms of Parkinson's disease in the TEMPO study. As adjunctive therapy to levodopa in the LARGO and PRESTO studies, rasagiline 0.5 and/or 1 mg/day significantly reduced the total daily 'off' time (primary efficacy endpoint) and significantly improved the Clinical Global Impression score, the UPDRS activities of daily living subscale score during 'off' time and the UPDRS

Inducible nitric oxide synthase gene methylation and parkinsonism in manganese-exposed welders

PubMed Central

Nielsen, Susan Searles; Checkoway, Harvey; Criswell, Susan R.; Farin, Federico M.; Stapleton, Patricia L.; Sheppard, Lianne; Racette, Brad A.

2015-01-01

Introduction Neurologist-assessed parkinsonism signs are prevalent among workers exposed to manganese (Mn)-containing welding fume. Neuroinflammation may possibly play a role. Inducible nitric oxide synthase, coded by NOS2, is involved in inflammation, and particulate exposure increases the gene’s expression through methylation of CpG sites in the 5′ region. Methods We assessed DNA methylation at three CpG sites in the NOS2 exon 1 from blood from 201 welders. All were non-Hispanic Caucasian men 25–65 years old who were examined by a neurologist specializing in movement disorders. We categorized the workers according to their Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3) scores as parkinsonism cases (UPDRS3 ≥ 15; n = 49), controls (UPDRS3 < 6; n = 103), or intermediate (UPDRS3 ≥6 to <15; n = 49). Results While accounting for age, examiner and experimental plate, parkinsonism cases had lower mean NOS2 methylation than controls (p-value for trend = 0.04), specifically at CpG site 8329 located in an exonic splicing enhancer of NOS2 (p-value for trend = 0.07). These associations were not observed for the intermediate UPDRS3 group (both p-value for trend ≥ 0.59). Conclusions Inflammation mediated by inducible nitric oxide synthase may possibly contribute to the association between welding fume and parkinsonism, but requires verification in a longitudinal study. PMID:25634431

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).…

Planning and task management in Parkinson's disease: differential emphasis in dual-task performance.

PubMed

Bialystok, Ellen; Craik, Fergus I M; Stefurak, Taresa

2008-03-01

Seventeen patients diagnosed with Parkinson's disease completed a complex computer-based task that involved planning and management while also performing an attention-demanding secondary task. The tasks were performed concurrently, but it was necessary to switch from one to the other. Performance was compared to a group of healthy age-matched control participants and a group of young participants. Parkinson's patients performed better than the age-matched controls on almost all measures and as well as the young controls in many cases. However, the Parkinson's patients achieved this by paying relatively less attention to the secondary task and focusing attention more on the primary task. Thus, Parkinson's patients can apparently improve their performance on some aspects of a multidimensional task by simplifying task demands. This benefit may occur as a consequence of their inflexible exaggerated attention to some aspects of a complex task to the relative neglect of other aspects.

Mitochondrial dynamics in Parkinson's disease: a role for α-synuclein?

PubMed

Pozo Devoto, Victorio M; Falzone, Tomas L

2017-09-01

The distinctive pathological hallmarks of Parkinson's disease are the progressive death of dopaminergic neurons and the intracellular accumulation of Lewy bodies enriched in α-synuclein protein. Several lines of evidence from the study of sporadic, familial and pharmacologically induced forms of human Parkinson's disease also suggest that mitochondrial dysfunction plays an important role in disease progression. Although many functions have been proposed for α-synuclein, emerging data from human and animal models of Parkinson's disease highlight a role for α-synuclein in the control of neuronal mitochondrial dynamics. Here, we review the α-synuclein structural, biophysical and biochemical properties that influence relevant mitochondrial dynamic processes such as fusion-fission, transport and clearance. Drawing on current evidence, we propose that α-synuclein contributes to the mitochondrial defects that are associated with the pathology of this common and progressive neurodegenerative disease. © 2017. Published by The Company of Biologists Ltd.

Syndromic parkinsonism and dementia associated with OPA 1 missense mutations

PubMed Central

Musumeci, Olimpia; Caporali, Leonardo; Zanna, Claudia; La Morgia, Chiara; Del Dotto, Valentina; Porcelli, Anna Maria; Rugolo, Michela; Valentino, Maria Lucia; Iommarini, Luisa; Maresca, Alessandra; Barboni, Piero; Carbonelli, Michele; Trombetta, Costantino; Valente, Enza Maria; Patergnani, Simone; Giorgi, Carlotta; Pinton, Paolo; Rizzo, Giovanni; Tonon, Caterina; Lodi, Raffaele; Avoni, Patrizia; Liguori, Rocco; Baruzzi, Agostino; Toscano, Antonio; Zeviani, Massimo

2015-01-01

Objective Mounting evidence links neurodegenerative disorders such as Parkinson disease and Alzheimer disease with mitochondrial dysfunction, and recent emphasis has focused on mitochondrial dynamics and quality control. Mitochondrial dynamics and mtDNA maintenance is another link recently emerged, implicating mutations in the mitochondrial fusion genes OPA1 and MFN2 in the pathogenesis of multisystem syndromes characterized by neurodegeneration and accumulation of mtDNA multiple deletions in postmitotic tissues. Here, we report 2 Italian families affected by dominant chronic progressive external ophthalmoplegia (CPEO) complicated by parkinsonism and dementia. Methods Patients were extensively studied by optical coherence tomography (OCT) to assess retinal nerve fibers, and underwent muscle and brain magnetic resonance spectroscopy (MRS), and muscle biopsy and fibroblasts were analyzed. Candidate genes were sequenced, and mtDNA was analyzed for rearrangements. Results Affected individuals displayed a slowly progressive syndrome characterized by CPEO, mitochondrial myopathy, sensorineural deafness, peripheral neuropathy, parkinsonism, and/or cognitive impairment, in most cases without visual complains, but with subclinical loss of retinal nerve fibers at OCT. Muscle biopsies showed cytochrome c oxidase‐negative fibers and mtDNA multiple deletions, and MRS displayed defective oxidative metabolism in muscle and brain. We found 2 heterozygous OPA1 missense mutations affecting highly conserved amino acid positions (p.G488R, p.A495V) in the guanosine triphosphatase domain, each segregating with affected individuals. Fibroblast studies showed a reduced amount of OPA1 protein with normal mRNA expression, fragmented mitochondria, impaired bioenergetics, increased autophagy and mitophagy. Interpretation The association of CPEO and parkinsonism/dementia with subclinical optic neuropathy widens the phenotypic spectrum of OPA1 mutations, highlighting the association of

Cellular replacement therapy for Parkinson's disease--where we are today?

PubMed

Redmond, D Eugene

2002-10-01

The concept of replacing lost dopamine neurons in Parkinson's disease using mesencephalic brain cells from fetal cadavers has been supported by over 20 years of research in animals and over a decade of clinical studies. The ambitious goal of these studies was no less than a molecular and cellular "cure" for Parkinson's disease, other neurodegenerative diseases, and spinal cord injury. Much research has been done in rodents, and a few studies have been done in nonhuman primate models. Early uncontrolled clinical reports were enthusiastic, but the outcome of the first randomized, double blind, controlled study challenged the idea that dopamine replacement cells can cure Parkinson's disease, although there were some significant positive findings. Were the earlier animal studies and clinical reports wrong? Should we give up on the goal? Some aspects of the trial design and implantation methods may have led to lack of effects and to some side effects such as dyskinesias. But a detailed review of clinical neural transplants published to date still suggests that neural transplantation variably reverses some aspects of Parkinson's disease, although differing methods make exact comparisons difficult. While the randomized clinical studies have been in progress, new methods have shown promise for increasing transplant survival and distribution, reconstructing the circuits to provide dopamine to the appropriate targets and with normal regulation. Selected promising new strategies are reviewed that block apoptosis induced by tissue dissection, promote vascularization of grafts, reduce oxidant stress, provide key growth factors, and counteract adverse effects of increased age. New sources of replacement cells and stem cells may provide additional advantages for the future. Full recovery from parkinsonism appears not only to be possible, but a reliable cell replacement treatment may finally be near.

Parkinson's disease: current and future challenges.

PubMed

Langston, J William

2002-10-01

In 15 years, we will mark the 200th anniversary of the James Parkinson's original description of the disease that now bears his name (An Essay on the Shaking Palsy, Sherwood, Neely and Jones London, 1817). Perhaps, one of the most exciting but daunting questions we face at this moment is whether or not we can unravel the etiology of the disease by that time. If we are to accomplish such an ambitious goal, we must determine the resources that will be required to make it happen, and identify the areas of scientific focus that should receive the greatest attention. One issue that will have great bearing on the allocation of research resources relates to the relative roles of genes versus environment in disease causation. For reasons that will become clear in this article, this has a remained surprisingly controversial area. Ironically, this controversy has even spilled over to the very definition of Parkinson's disease, and even whether or not it should be considered a disease entity. In this article, the enduring "genes versus environment" debate is reviewed, with a goal of putting it into a broader perspective. Issues surrounding disease definition and terminology are also addressed in detail, because of the need to have clarity of thought and vision if research on the cause is to proceed in an orderly (and hopefully expeditious) manner. Finally, issues relating future research directions are summarized, with the goal of identifying the pieces of the Parkinson's puzzle that are going to have to be put together if we are to solve this mysterious disease.

Parkinson's disease patients undershoot target size in handwriting and similar tasks

PubMed Central

Van Gemmert, A W A; Adler, C; Stelmach, G

2003-01-01

Objectives:Previous research suggested that people with Parkinson's disease are able to increase handwriting stroke size up to 1.5 cm without an increase of stroke duration; whereas age matched individuals in normal health are able to modulate stroke size without changes in stroke duration for sizes up to 2 cm. This study was designed to test this finding by examining whether sizes larger than 1.5 cm show different relationships with stroke duration for patients with Parkinson's disease as compared with age matched controls. Methods:The study included 13 subjects with Parkinson's disease and 13 age matched controls. Participants were required to write a cursive "llllllll" pattern, or a cursive "lililili" pattern without the dots, at a comfortable speed and also as fast as possible, in five different sizes (1.0, 1.5, 2.0, 3.0, and 5.0 cm). The participants wrote with a ballpoint pen on a digitiser tablet. The target pattern was displayed at its required size on a screen, but disappeared as soon as the pen touched the surface of the digitiser tablet. Online visual monitoring of the hand was prevented by a cover over the digitiser. After each trial, the recorded movement of the tip of the pen was displayed with two lines to indicate whether the size requirement had been met. The writing conditions were presented in random order and consisted of 12 trials for each participant. Results:The results demonstrated that stroke size and duration produced by the participants with Parkinson's disease were independently modulated up to 1.5 cm; sizes over 1.5 cm resulted in progressive undershooting by patients with Parkinson's disease (PD). It was also shown that these participants modulated acceleration measures inefficiently as compared with controls. Conclusions:The findings suggest that individuals with Parkinson's disease writing at speed produce inadequate stroke sizes when these should equal or exceed 1.5 cm. PMID:14617705

Factors supporting self-management in Parkinson's disease: implications for nursing practice.

PubMed

Chenoweth, Lynn; Gallagher, Robyn; Sheriff, June N; Donoghue, Judith; Stein-Parbury, Jane

2008-09-01

Aim.  To identify the factors associated with better self-management in people with moderate to high levels of Parkinson's disease following an acute illness event. Design and methods.  A prospective, descriptive study conducted with 75 persons with Parkinson's disease over the age of 55, collected twice: within a week of an acute event and 1 month later, after resuming usual life at home. Participants completed a questionnaire on self-rated health status, self-efficacy, sense of coherence, symptom monitoring and medication and general self-management. Background.  Parkinson's disease is a chronic neurological condition that affects many dimensions of life, including threats to self-identity and confidence in self-management. Self-management has the potential to reduce costs through decreased hospital admissions, disease progression and avoidance of complications. While evidence for the relationships between self-management and self-efficacy and sense of coherence has been demonstrated in some chronic illness groups, this has not previously been demonstrated in Parkinson's disease. Results.  The independent predictors of better self-management were not being hospitalized in the last 6 months, more frequent symptom checking and better self-efficacy for self-management. The influence of other factors on self-management, such as sense of coherence, was mediated through self-efficacy. Support of family and others was associated with better self-efficacy both directly and through an improved sense of coherence. Conclusions and relevance to nursing practice.  The presence of informal support plays an important role in sustaining self-efficacy and sense of coherence and hence self-management in persons with Parkinson's disease. Since these attributes are amenable to change, nurses are in a good position to encourage participation in Parkinson's support groups, teach self-management skills through regular symptom monitoring and to assess and promote self

Temporal prolongation of decreased skin blood flow causes cold limbs in Parkinson's disease.

PubMed

Shindo, Kazumasa; Kobayashi, Fumikazu; Miwa, Michiaki; Nagasaka, Takamura; Takiyama, Yoshihisa; Shiozawa, Zenji

2013-03-01

To unravel the pathogenesis of cold limbs in Parkinson's disease, we evaluated cutaneous vasomotor neural function in 25 Parkinson's disease patients with or without cold limbs and 20 healthy controls. We measured resting skin sympathetic nerve activity, as well as reflex changes of skin blood flow and skin sympathetic nerve activity after electrical stimulation, with the parameters including skin sympathetic nerve activity frequency at rest, the amplitude of reflex bursts, the absolute decrease and percent reduction of blood flow, and the recovery time which was calculated as the interval from the start of blood flow reduction until the return to baseline cutaneous blood flow. The resting frequency of skin sympathetic nerve activity was significantly lower in patients with Parkinson's disease than in controls (p < 0.01). There were no significant differences between the patients and controls with respect to the amplitude of skin sympathetic nerve activity and the absolute decrease or percent reduction of blood flow volume. In the controls, the recovery time (9.4 ± 1.2), which was similar to Parkinson's disease patients without cold limbs (9.0 ± 0.7), while the recovery time ranged (15.7 ± 3.2) in Parkinson's disease patients with cold limbs. Recovery was significantly slower in these patients compared with the other groups (p < 0.05). It is possible that cold limbs might arise due to impaired circulation based on prolonged vasoconstriction by peripheral autonomic impairments, in addition to central autonomic dysfunction in Parkinson's disease.

Locus Coeruleus Neuron Density and Parkinsonism in Older Adults without Parkinson’s Disease

PubMed Central

Buchman, Aron S.; Nag, Sukriti; Shulman, Joshua M.; Lim, Andrew S.P.; VanderHorst, Veronique G.J.M.; Leurgans, Sue E.; Schneider, Julie A.; Bennett, David A.

2013-01-01

Objective Prior work has showed that nigral neuron density is related to the severity of parkinsonism proximate to death in older persons without a clinical diagnosis of Parkinson’s disease (PD). We tested the hypothesis that neuron density in other brainstem aminergic nuclei is also related to the severity of parkinsonism. Design We studied brain autopsies from 125 deceased older adults without PD enrolled in the Memory and Aging Project, a clinical-pathologic investigation. Parkinsonism was assessed with a modified version of the Unified Parkinson’s Disease Rating Scale (UPDRS). We measured neuron density in the substantia nigra, ventral tegmental area, locus coeruleus and dorsal raphe; and postmortem indices of Lewy body Alzheimer’s disease and cerebrovascular pathologies. Results Mean age at death was 88.0 and global parkinsonism was 14.8 (SD=9.50). In a series of regression models which controlled for demographics and neuron density in the substantia nigra, neuron density in the locus coeruleus (Estimate, −0.261, S.E., 0.117, p=0.028) but not in the ventral tegmental area or dorsal raphe was associated with the severity of global parkinsonism proximate to death. These findings were unchanged in models which controlled for post-mortem interval, whole brain weight and other common neuropathologies including Alzheimer’s disease and Lewy body pathology and cerebrovascular vascular pathologies. Conclusion In older adults without a clinical diagnosis of PD, neuron density in locus coeruleus nuclei is associated with the severity of parkinsonism and may contribute to late-life motor impairments. PMID:23038629

Freezing of gait is associated with cognitive impairment in patients with Parkinson disease.

PubMed

Yao, Zhiwen; Shao, Yuan; Han, Xiang

2017-08-24

To explore whether the cognitive impairment is correlated with freezing of gait (FOG) in patients with Parkinson disease (PD). A total of 186 patients with Parkinson disease (104 patients with FOG and 82 patients with no clinical history of freezing behavior) and 125 healthy individuals were selected for this study. Neuropsychological assessments, including the scales for outcomes in Parkinson disease cognition, unified Parkinson's disease rating scale, and Hamilton depression/anxiety rating scale etc., were applied to evaluate the patients'cognitive functioning. We found that the scores of Unified Parkinson's Disease Rating Scale (UPDRS) were significantly higher among PD patients with FOG, compared with non-FOG group. We also showed that Mini-Mental State Examination score (MMSE) was lower among subjects with FOG than in patients without FOG. Patients with FOG displayed lower Scales for OUTCOMES: in Parkinson's Disease Cognition (SCOPA-COG) score than non-FOG patients. In addition, significant higher Hamilton Anxiety Rating Scale (HAMD) scores were found in patients with FOG than patients without FOG. Moreover, disease duration, stage of the disease, the severity of motor symptom, increased depressive and anxiety complaints measured by FOG questionnaire were significantly associated with severity of FOG. Meanwhile, we also found that the score of Freezing of Gait Questionnaire (FOGQ) score was negatively correlated with MMSE. Our results demonstrated that FOG is related to impaired cognitive functions in PD patients with FOG. The understanding of impaired cognitive functions in PD patients with FOG can provide evidences for possible therapeutic interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

Cardiovascular aspects of Parkinson disease.

PubMed

Goldstein, D S

2006-01-01

This chapter provides an update about cardiovascular aspects of Parkinson disease (PD), with the following topics: (1) Orthostatic hypotension (OH) as an early finding in PD; (2) neurocirculatory abnormalities in PD + OH independent of levodopa treatment; (3) cardiac and extracardiac noradrenergic denervation in PD + OH; (4) progressive loss of cardiac sympathetic innervation in PD without OH.

Psychosis in Parkinson's Disease.

PubMed

Ffytche, Dominic H; Aarsland, Dag

2017-01-01

Although illusions, hallucinations and delusions did not play a prominent role in James Parkinson's original clinical descriptions, the longitudinal view of disease progression he advocated has important lessons for the study of such symptoms today. A focus on longitudinal progression rather than individual symptoms led to the concept of PD psychosis-a spectrum of positive symptoms in Parkinson's disease. The publication of criteria for PD psychosis in 2007 helped unify the disparate set of symptoms, raising their profile and resulting in a rapid expansion of literature focussing on clinical aspects, mechanisms, and treatment. Here we review this literature and the evolving view of PD psychosis. Adding to previous evidence of a prospective risk for dementia and the move to supervised care, key recent developments include: recognition of prevalence increase with disease duration; a broadening of symptoms included in PD psychosis; better characterization of higher visual and cognitive dysfunction risk factors; structural, functional, and neurotransmitter imaging biomarker evidence; and approval of pimavanserin in the United States for the treatment of PD psychosis. The accumulating evidence raises novel questions and directions for future research that promise a better understanding of the clinical management of PD psychosis and its role as a biomarker for PD stage and progression. © 2017 Elsevier Inc. All rights reserved.

Exercise for falls prevention in Parkinson disease

PubMed Central

Sherrington, Catherine; Lord, Stephen R.; Close, Jacqueline C.T.; Heritier, Stephane; Heller, Gillian Z.; Howard, Kirsten; Allen, Natalie E.; Latt, Mark D.; Murray, Susan M.; O'Rourke, Sandra D.; Paul, Serene S.; Song, Jooeun; Fung, Victor S.C.

2015-01-01

Objective: To determine whether falls can be prevented with minimally supervised exercise targeting potentially remediable fall risk factors, i.e., poor balance, reduced leg muscle strength, and freezing of gait, in people with Parkinson disease. Methods: Two hundred thirty-one people with Parkinson disease were randomized into exercise or usual-care control groups. Exercises were practiced for 40 to 60 minutes, 3 times weekly for 6 months. Primary outcomes were fall rates and proportion of fallers during the intervention period. Secondary outcomes were physical (balance, mobility, freezing of gait, habitual physical activity), psychological (fear of falling, affect), and quality-of-life measures. Results: There was no significant difference between groups in the rate of falls (incidence rate ratio [IRR] = 0.73, 95% confidence interval [CI] 0.45–1.17, p = 0.18) or proportion of fallers (p = 0.45). Preplanned subgroup analysis revealed a significant interaction for disease severity (p < 0.001). In the lower disease severity subgroup, there were fewer falls in the exercise group compared with controls (IRR = 0.31, 95% CI 0.15–0.62, p < 0.001), while in the higher disease severity subgroup, there was a trend toward more falls in the exercise group (IRR = 1.61, 95% CI 0.86–3.03, p = 0.13). Postintervention, the exercise group scored significantly (p < 0.05) better than controls on the Short Physical Performance Battery, sit-to-stand, fear of falling, affect, and quality of life, after adjusting for baseline performance. Conclusions: An exercise program targeting balance, leg strength, and freezing of gait did not reduce falls but improved physical and psychological health. Falls were reduced in people with milder disease but not in those with more severe Parkinson disease. Classification of evidence: This study provides Class III evidence that for patients with Parkinson disease, a minimally supervised exercise program does not reduce fall risk. This study lacked

[SCA6 presenting parkinsonism without ataxia--A case report].

PubMed

Takeshima, Shinichi; Takeda, Ikuko; Kobatake, Keitaro; Yamashita, Toru; Abe, Koji; Kuriyama, Masaru

2015-01-01

A 57-year-old man was admitted to our hospital because of bradykinesia. He was diagnosed with Parkinson disease (Hoehn and Yahr grade 2) and administered levodopa at the maximum dose of 800 mg. However, his condition did not improve. While his symptoms were responsive to levodopa therapy, the sensitivity to the drug was poor. Brain MRI revealed atrophy of the upper vermis and cerebral hemispheres, and brain SPECT revealed low perfusion in both parietal lobes. I(123)-metaiodobenzylguanidine scintigraphy showed a decrease in the heart/mediastinum ratio. Striatal dopamine transporter (DAT) density was evaluated using I(123)-FP-CIT. The patient showed moderately reduced DAT density, which suggested nigrostriatal dopaminergic damage. His mother was found to have pure cerebellar ataxia without parkinsonism, and her two siblings also had celebellar type of multiple system atrophy (MSA-C) and progressive supranuclear palsy, respectively. Genetic testing revealed that the patient, his mother and the uncle with MSA-C had spinocerebellar ataxia type 6 (SCA6). SCA6 presenting parkinsonism without ataxia is very rare and important for the pathomechanism of disease.

Wolff-Parkinson-White Syndrome in a Term Infant Presenting With Cardiopulmonary Arrest.

PubMed

Hoeffler, Christina D; Krenek, Michele E; Brand, M Colleen

2016-02-01

Wolff-Parkinson-White syndrome is a congenital abnormality of the cardiac conduction system caused by the presence of an abnormal accessory electrical pathway between the atria and the ventricles. This can result in intermittent tachyarrhythmias such as supraventricular tachycardia. In rare occasions, sudden death may occur from atrial fibrillation with rapid ventricular conduction. Supraventricular tachycardia typically has a sudden onset and offset, classified as a paroxysmal arrhythmia. Because of the variable occurrence, Wolff-Parkinson-White syndrome may go undiagnosed in the immediate newborn period. To highlight arrhythmia as a possible cause of sudden decompensation in infants. The clinical presentation of this infant is complex and a number of potential diagnoses were considered. Preexcitation on electrocardiogram resulted in the diagnosis of Wolff-Parkinson-White syndrome. Nurses caring for infants should be alert to tachycardia and irregularities of the heart rate, including those in the prenatal history, and should report them for evaluation. While all parents should be taught to watch for signs of illness, parents of infants with Wolff-Parkinson-White have additional learning needs, including recognizing early signs and symptoms of heart failure.

Agricultural work and the risk of Parkinson's disease in Denmark, 1981-1993.

PubMed

Tüchsen, F; Jensen, A A

2000-08-01

This study examined the possible association between agricultural and horticultural work and the subsequent morbidity of Parkinson's disease. Fixed cohorts of 2,273,872 men and women aged 20-59 years on 1 January 1981 and identified in the Central Population Register of Denmark were followed, and all first-time hospitalizations with Parkinson's disease as the principal diagnosis during the 13 years until 31 December 1993 were recorded. Standardized hospitalization ratios (SHR) were calculated using all gainfully employed persons as the standard and by multiplying the ratio by 100. Ninety-five percent confidence intervals (95% CI) were calculated on the assumption of a Poisson distribution. A high risk of Parkinson's disease was found for the men and women in agriculture and horticulture (134 cases, SHR 132, 95% CI 111-156). Statistically significantly high risks were found for farmers (79 cases, SHR 130, 95% CI 103-163) and for all men in agriculture and horticulture (109 cases, SHR 134, 95% CI 109-162). A consistent pattern of high Parkinson's disease morbidity was found among occupational groups employed in agriculture and horticulture.

Meta-analysis: Association of Helicobacter pylori infection with Parkinson's diseases.

PubMed

Shen, Xiaoli; Yang, Huazhen; Wu, Yili; Zhang, Dongfeng; Jiang, Hong

2017-10-01

The results from observational studies on the relationship between helicobacter pylori (H. pylori) infection and Parkinson's disease remain controversial. A meta-analysis was conducted to evaluate the association between helicobacter pylori infection and Parkinson's disease. A comprehensive literature search was performed on relevant studies published from January 1983 to January 2017 in PubMed, Web of Science and EMBASE databases. The fixed or random effects model was used to pool the odds ratio with 95% confidence interval from individual studies. Publication bias was estimated by Egger's test and the funnel plot. Eight eligible studies involving 33 125 participants were included in this meta-analysis. Compared with the no helicobacter pylori infected person, the pooled odds ratio of Parkinson's disease in helicobacter pylori infected person was 1.59 (95% confidence interval: 1.37-1.85). In subgroup analyzes, the combined odds ratios were 1.96 (1.23-3.12) in Asia, 1.55 (1.32-1.82) in Europe, 1.59 (1.35-1.88) in case-control studies, 1.56 (1.01-2.39) in cross-sectional studies, 1.56 (1.32-1.85) in studies with confounders adjusted, and 1.71 (1.21-2.43) in studies with no confounder adjusted, respectively. This meta-analysis indicated that H. pylori infection might be associated with the risk of Parkinson's disease. © 2017 John Wiley & Sons Ltd.

Treadmill exercise alleviates short-term memory impairment in 6-hydroxydopamine-induced Parkinson's rats.

PubMed

Cho, Han-Sam; Shin, Mal-Soon; Song, Wook; Jun, Tae-Won; Lim, Baek-Vin; Kim, Young-Pyo; Kim, Chang-Ju

2013-01-01

Progressive loss of dopaminergic neurons in substantia nigra is a key pathogenesis of Parkinson's disease. In the present study, we investigated the effects of treadmill exercise on short-term memory, apoptotic dopaminergic neuronal cell death and fiber loss in the nigrostriatum, and cell proliferation in the hippocampal dentate gyrus of Parkinson's rats. Parkinson's rats were made by injection of 6-hydroxydopamine (6-OHDA) into the striatum using stereotaxic instrument. Four weeks after 6-OHDA injection, the rats in the 6-OHDA-injection group exhibited significant rotational asymmetry following apomorphine challenge. The rats in the exercise groups were put on the treadmill to run for 30 min once a day for 14 consecutive days starting 4 weeks after 6-OHDA injection. In the present results, extensive degeneration of the dopaminergic neurons in the substantia nigra with loss of dopaminergic fibers in the striatum were produced in the rats without treadmill running, which resulted in short-term memory impairment. However, the rats performing treadmill running for 2 weeks alleviated nigrostriatal dopaminergic cell loss and alleviated short-term memory impairment with increasing cell proliferation in the hippocampal dentate gyrus of Parkinson's rats. The present results show that treadmill exercise may provide therapeutic value for the Parkinson's disease.

Uncovering the role of the insula in non-motor symptoms of Parkinson's disease.

PubMed

Christopher, Leigh; Koshimori, Yuko; Lang, Anthony E; Criaud, Marion; Strafella, Antonio P

2014-08-01

Patients with Parkinson's disease experience a range of non-motor symptoms, including cognitive impairment, behavioural changes, somatosensory and autonomic disturbances. The insula, which was once thought to be primarily a limbic cortical structure, is now known to be highly involved in integrating somatosensory, autonomic and cognitive-affective information to guide behaviour. Thus, it acts as a central hub for processing relevant information related to the state of the body as well as cognitive and mood states. Despite these crucial functions, the insula has been largely overlooked as a potential key region in contributing to non-motor symptoms of Parkinson's disease. The insula is affected in Parkinson's disease by alpha-synuclein deposition, disruptions in normal neurotransmitter function, alterations in connectivity as well as metabolic and structural changes. Although research focusing on the role of the insula in Parkinson's disease is scarce, there is evidence from neuroimaging studies linking the insula to cognitive decline, behavioural abnormalities and somatosensory disturbances. Here, we review imaging studies that provide insight into the potential role of the insula in Parkinson's disease non-motor symptoms. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Herbal Prescriptions and Medicinal Herbs for Parkinson-Related Rigidity in Korean Medicine: Identification of Candidates Using Text Mining.

PubMed

Park, So Hyun; Hwang, Min Seob; Park, Hye Jin; Shin, Hwa Kyoung; Baek, Jin Ung; Choi, Byung Tae

2018-03-27

Dongeuibogam (DongYiBaoGian), one of the most important books in Korean medicine, comprises a comprehensive summary of all traditional medicines of North-East Asia before the 17th century. This medicinal literature was mined to establish a list of candidate herbs to treat Parkinson-related rigidity. A systematic search for terms describing Parkinson-related rigidity and candidate prescriptions for the treatment of Parkinson-related rigidity in the Dongeuibogam was performed. A high-frequency medicinal herb combination group and candidates for the treatment of Parkinson-related rigidity were also selected through an analysis of medicinal herb combination frequencies. The existing literature pertaining to the potential effects of candidate herbs for Parkinson-related rigidity was reviewed. Ten medicinal herb candidates for the treatment of Parkinson-related rigidity were selected, and their respective precedent studies were analyzed.

Phosphorus and proton magnetic resonance spectroscopy demonstrates mitochondrial dysfunction in early and advanced Parkinson's disease.

PubMed

Hattingen, Elke; Magerkurth, Jörg; Pilatus, Ulrich; Mozer, Anne; Seifried, Carola; Steinmetz, Helmuth; Zanella, Friedhelm; Hilker, Rüdiger

2009-12-01

Mitochondrial dysfunction hypothetically contributes to neuronal degeneration in patients with Parkinson's disease. While several in vitro data exist, the measurement of cerebral mitochondrial dysfunction in living patients with Parkinson's disease is challenging. Anatomical magnetic resonance imaging combined with phosphorus and proton magnetic resonance spectroscopic imaging provides information about the functional integrity of mitochondria in specific brain areas. We measured partial volume corrected concentrations of low-energy metabolites and high-energy phosphates with sufficient resolution to focus on pathology related target areas in Parkinson's disease. Combined phosphorus and proton magnetic resonance spectroscopic imaging in the mesostriatal region was performed in 16 early and 13 advanced patients with Parkinson's disease and compared to 19 age-matched controls at 3 Tesla. In the putamen and midbrain of both Parkinson's disease groups, we found a bilateral reduction of high-energy phosphates such as adenosine triphophosphate and phosphocreatine as final acceptors of energy from mitochondrial oxidative phosphorylation. In contrast, low-energy metabolites such as adenosine diphophosphate and inorganic phosphate were within normal ranges. These results provide strong in vivo evidence that mitochondrial dysfunction of mesostriatal neurons is a central and persistent phenomenon in the pathogenesis cascade of Parkinson's disease which occurs early in the course of the disease.

Role of dysphagia in evaluating Parkinson patients for subthalamic nucleus stimulation: a case report.

PubMed

Allert, Niels; Kelm, Daniela; Spottke, Annika; Coenen, Volker A

2011-09-01

In the selection of Parkinson patients for deep brain stimulation (DBS) of the subthalamic nucleus (STN) a risk-benefit-analysis is performed regarding symptoms that commonly improve and symptoms that may deteriorate. Speech is among the symptoms that may deteriorate. In contrast, the differential effects of STN-DBS on swallowing are less clear. Here, we present a Parkinson patient with dysphagia from concomitant oculo-pharyngeal muscle dystrophy successfully treated by STN-DBS. The role of dysphagia in evaluating Parkinson patients for STN-DBS is discussed.

Protein degradation pathways in Parkinson's disease: curse or blessing.

PubMed

Ebrahimi-Fakhari, Darius; Wahlster, Lara; McLean, Pamela J

2012-08-01

Protein misfolding, aggregation and deposition are common disease mechanisms in many neurodegenerative diseases including Parkinson's disease (PD). Accumulation of damaged or abnormally modified proteins may lead to perturbed cellular function and eventually to cell death. Thus, neurons rely on elaborated pathways of protein quality control and removal to maintain intracellular protein homeostasis. Molecular chaperones, the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP) are critical pathways that mediate the refolding or removal of abnormal proteins. The successive failure of these protein degradation pathways, as a cause or consequence of early pathological alterations in vulnerable neurons at risk, may present a key step in the pathological cascade that leads to spreading neurodegeneration. A growing number of studies in disease models and patients have implicated dysfunction of the UPS and ALP in the pathogenesis of Parkinson's disease and related disorders. Deciphering the exact mechanism by which the different proteolytic systems contribute to the elimination of pathogenic proteins, like α-synuclein, is therefore of paramount importance. We herein review the role of protein degradation pathways in Parkinson's disease and elaborate on the different contributions of the UPS and the ALP to the clearance of altered proteins. We examine the interplay between different degradation pathways and provide a model for the role of the UPS and ALP in the evolution and progression of α-synuclein pathology. With regards to exciting recent studies we also discuss the putative potential of using protein degradation pathways as novel therapeutic targets in Parkinson's disease.

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

Evolution of diagnostic criteria and assessments for Parkinson's disease mild cognitive impairment.

PubMed

Goldman, Jennifer G; Holden, Samantha K; Litvan, Irene; McKeith, Ian; Stebbins, Glenn T; Taylor, John-Paul

2018-04-01

Mild cognitive impairment has gained recognition as a construct and a potential prodromal stage to dementia in both Alzheimer's disease and Parkinson's disease (PD). Although mild cognitive impairment has been recognized in the Alzheimer's disease field, it is a relatively more recent topic of interest in PD. Recent advances include the development of diagnostic criteria for PD mild cognitive impairment to provide more uniform definitions for clinical and research use. Studies reveal that mild cognitive impairment in PD is frequent, but also heterogeneous, with variable clinical presentations, differences in its progression to dementia, and likely differences in underlying pathophysiology. Application of the International Parkinson and Movement Disorder Society PD Mild Cognitive Impairment Task Force diagnostic criteria has provided insights regarding cognitive measures, functional assessments, and other key topics that may require additional refinement. Furthermore, it is important to consider definitions of PD mild cognitive impairment in the landscape of other related Lewy body disorders, such as dementia with Lewy bodies, and in the context of prodromal and early-stage PD. This article examines the evolution of mild cognitive impairment in concept and definition, particularly in PD, but also in related disorders such as Alzheimer's disease and dementia with Lewy bodies; the development and application of International Parkinson and Movement Disorder Society PD Mild Cognitive Impairment diagnostic criteria; and insights and future directions for the field of PD mild cognitive impairment. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

A process-model based approach to prospective memory impairment in Parkinson's disease.

PubMed

Kliegel, Matthias; Altgassen, Mareike; Hering, Alexandra; Rose, Nathan S

2011-07-01

The present review discusses the current state of research on the clinical neuropsychology of prospective memory in Parkinson's disease. To do so the paper is divided in two sections. In the first section, we briefly outline key features of the (partly implicit) rationale underlying the available literature on the clinical neuropsychology of prospective memory. Here, we present a conceptual model that guides our approach to the clinical neuropsychology of prospective memory in general and to the effects of Parkinson's disease on prospective memory in particular. In the second section, we use this model to guide our review of the available literature and suggest some open issues and future directions motivated by previous findings and the proposed conceptual model. The review suggests that certain phases of the prospective memory process (intention formation und initiation) are particularly impaired by Parkinson's disease. In addition, it is argued that prospective memory may be preserved when tasks involve specific features (e.g., focal cues) that reduce the need for strategic monitoring processes. In terms of suggestions for future directions, it is noted that intervention studies are needed which target the specific phases of the prospective memory process that are impaired in Parkinson's disease, such as planning interventions. Moreover, it is proposed that prospective memory deficits in Parkinson's disease should be explored in the context of a general impairment in the ability to form an intention and plan or coordinate an appropriate series of actions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Parkinson's disease-related fatigue: A case definition and recommendations for clinical research.

PubMed

Kluger, Benzi M; Herlofson, Karen; Chou, Kelvin L; Lou, Jau-Shin; Goetz, Christopher G; Lang, Anthony E; Weintraub, Daniel; Friedman, Joseph

2016-05-01

Fatigue is one of the most common and disabling symptoms in Parkinson's disease (PD). Since fatigue was first described as a common feature of PD 20 years ago, little progress has been made in understanding its causes or treatment. Importantly, PD patients attending the 2013 World Parkinson Congress voted fatigue as the leading symptom in need of further research. In response, the Parkinson Disease Foundation and ProjectSpark assembled an international team of experts to create recommendations for clinical research to advance this field. The working group identified several areas in which shared standards would improve research quality and foster progress including terminology, diagnostic criteria, and measurement. Terminology needs to (1) clearly distinguish fatigue from related phenomena (eg, sleepiness, apathy, depression); (2) differentiate subjective fatigue complaints from objective performance fatigability; and (3) specify domains affected by fatigue and causal factors. We propose diagnostic criteria for PD-related fatigue to guide participant selection for clinical trials and add rigor to mechanistic studies. Recommendations are made for measurement of subjective fatigue complaints, performance fatigability, and neurophysiologic changes. We also suggest areas in which future research is needed to address methodological issues and validate or optimize current practices. Many limitations in current PD-related fatigue research may be addressed by improving methodological standards, many of which are already being successfully applied in clinical fatigue research in other medical conditions (eg, cancer, multiple sclerosis). © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Prevalence and risk factors of Parkinson's disease in retired Thai traditional boxers.

PubMed

Lolekha, Praween; Phanthumchinda, Kammant; Bhidayasiri, Roongroj

2010-09-15

Boxing is often believed to be a frequent cause for parkinsonism caused by chronic repetitive head injury, with Muhammad Ali frequently cited as an example. The purpose of this study is to determine the prevalence of Parkinson's disease (PD) in retired Thai traditional boxers. Two standardized screening questionnaires were sent to all registered Thai traditional boxers. Subjects who screened positive for parkinsonism were invited for clinical examinations by two independent neurologists. Among 704 boxers (70%) who completed the questionnaires, 8 boxers (1.14%) had parkinsonism: 5 with PD, 1 with progressive supranuclear palsy and 2 with vascular parkinsonism. Boxers with PD were found to have an older mean age than those without PD (P = 0.003). The analysis of probable risk factors disclosed an association between the number of professional bouts (>100 times) and PD (P = 0.01). The crude prevalence of PD in Thai boxers was 0.71% (95% CI: 0.09-1.33), with a significant increase with age. The prevalence rate of PD in those aged 50 and above was 0.17% (95% CI: 0.15-0.20), age-adjusted to the USA 1970 census, which is comparable to that of the general populations. The analysis determined that the number of professional bouts is a risk factor among these boxers, supporting the notion that repetitive head trauma may pose an additional risk to certain individuals who are already susceptible to PD. © 2010 Movement Disorder Society.

[Digestive disorders in Parkinson's disease: dysphagia and sialorrhea].

PubMed

González-Fernández, J; Prieto-Albin, R; Velasco-Palacios, L; Jorge-Roldán, S; Cubo-Delgado, E

2010-02-08

The non-motor symptoms of Parkinson's disease are a frequent and often under-diagnosed disorder. Two of the most significant non-motor symptoms are perhaps dysphagia and sialorrhea (which are relatively common in advanced stages of the disease) owing to their important functional repercussions and to the associated comorbidity. In recent years, different evaluation scales have been developed for clinical use and in screening the aforementioned symptoms. Of the different therapeutic options available, botulinum toxin represents the preferred treatment for sialorrhea. In contrast, speech therapy and an optimisation of the antiparkinsonian therapy are generally useful measures to treat dysphagia, percutaneous endoscopic gastrostomy being reserved for patients suffering from Parkinson who have severe dysphagia.

Aging and Parkinson's disease: Different sides of the same coin?

PubMed

Collier, Timothy J; Kanaan, Nicholas M; Kordower, Jeffrey H

2017-07-01

Despite abundant epidemiological evidence in support of aging as the primary risk factor for PD, biological correlates of a connection have been elusive. In this article, we address the following question: does aging represent biology accurately characterized as pre-PD? We present evidence from our work on midbrain dopamine neurons of aging nonhuman primates that demonstrates that markers of known correlates of dopamine neuron degeneration in PD, including impaired proteasome/lysosome function, oxidative/nitrative damage, and inflammation, all increase with advancing age and are exaggerated in the ventral tier substantia nigra dopamine neurons most vulnerable to degeneration in PD. Our findings support the view that aging-related changes in the dopamine system approach the biological threshold for parkinsonism, actively producing a vulnerable pre-parkinsonian state. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Targeted therapies for Parkinson's disease: From genetics to the clinic.

PubMed

Sardi, S Pablo; Cedarbaum, Jesse M; Brundin, Patrik

2018-04-27

The greatest unmet medical need in Parkinson's disease (PD) is treatments that slow the relentless progression of symptoms. The discovery of genetic variants causing and/or increasing the risk for PD has provided the field with a new arsenal of potential therapies ready to be tested in clinical trials. We highlight 3 of the genetic discoveries (α-synuclein, glucocerebrosidase, and leucine-rich repeat kinase) that have prompted new therapeutic approaches now entering the clinical stages. We are at an exciting juncture in the journey to developing disease-modifying treatments based on knowledge of PD genetics and pathology. This review focuses on therapeutic paradigms that are under clinical development and highlights a wide range of key outstanding questions in PD. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Motor phenotype and magnetic resonance measures of basal ganglia iron levels in Parkinson's disease☆

PubMed Central

Bunzeck, Nico; Singh-Curry, Victoria; Eckart, Cindy; Weiskopf, Nikolaus; Perry, Richard J.; Bain, Peter G.; Düzel, Emrah; Husain, Masud

2013-01-01

Background In Parkinson's disease the degree of motor impairment can be classified with respect to tremor dominant and akinetic rigid features. While tremor dominance and akinetic rigidity might represent two ends of a continuum rather than discrete entities, it would be important to have non-invasive markers of any biological differences between them in vivo, to assess disease trajectories and response to treatment, as well as providing insights into the underlying mechanisms contributing to heterogeneity within the Parkinson's disease population. Methods Here, we used magnetic resonance imaging to examine whether Parkinson's disease patients exhibit structural changes within the basal ganglia that might relate to motor phenotype. Specifically, we examined volumes of basal ganglia regions, as well as transverse relaxation rate (a putative marker of iron load) and magnetization transfer saturation (considered to index structural integrity) within these regions in 40 individuals. Results We found decreased volume and reduced magnetization transfer within the substantia nigra in Parkinson's disease patients compared to healthy controls. Importantly, there was a positive correlation between tremulous motor phenotype and transverse relaxation rate (reflecting iron load) within the putamen, caudate and thalamus. Conclusions Our findings suggest that akinetic rigid and tremor dominant symptoms of Parkinson's disease might be differentiated on the basis of the transverse relaxation rate within specific basal ganglia structures. Moreover, they suggest that iron load within the basal ganglia makes an important contribution to motor phenotype, a key prognostic indicator of disease progression in Parkinson's disease. PMID:24025315

Impulsive Behavior and Associated Clinical Variables in Parkinson's Disease

PubMed Central

Abosch, Aviva; Gupte, Akshay; Eberly, Lynn E.; Tuite, Paul J.; Nance, Martha; Grant, Jon E.

2011-01-01

Parkinson's disease (PD) is a degenerative brain disorder accompanied by the loss of dopaminergic neurons and the presence of motor and non-motor symptoms. We performed a cross-sectional, questionnaire-based analysis of impulsive behavior in our PD clinic population to assess prevalence and associated characteristics. We found a higher prevalence of impulsive behavior (29.7%) than previously reported, and found multiple, concurrent impulsive behaviors in 26% of subjects reporting impulsive behavior. Our findings contribute to the growing awareness of impulsive behavior in PD, and support the need for longitudinal studies to assess changes in impulsive behaviors in Parkinson's patients. PMID:21300194

Young onset Parkinson's disease. Practical management of medical issues.

PubMed

Calne, Susan M; Kumar, Ajit

2008-01-01

Young Onset Parkinson's disease (YOPD) is defined as Parkinson's disease diagnosed between the ages of 21 and 40 years. Problems faced by this group are different from those faced by older subjects because they face decades with the illness. This article reviews current literature and offers suggestions for intervention when appropriate and practical suggestions in the areas of drug treatment, rehabilitation, nutrition, sexuality, pregnancy, menstruation and menopause. The suggestions are not exclusively restricted to the management of YOPD, but emphasis is placed on items where people with YOPD have either had particular difficulties or where they can proactively self-manage their illness.

Habitual versus goal-directed action control in Parkinson disease.

PubMed

de Wit, Sanne; Barker, Roger A; Dickinson, Anthony D; Cools, Roshan

2011-05-01

This study presents the first direct investigation of the hypothesis that dopamine depletion of the dorsal striatum in mild Parkinson disease leads to impaired stimulus-response habit formation, thereby rendering behavior slow and effortful. However, using an instrumental conflict task, we show that patients are able to rely on direct stimulus-response associations when a goal-directed strategy causes response conflict, suggesting that habit formation is not impaired. If anything our results suggest a disease severity-dependent deficit in goal-directed behavior. These results are discussed in the context of Parkinson disease and the neurobiology of habitual and goal-directed behavior.

Evaluation of Parkinson disease and Alzheimer disease with the use of neuromelanin MR imaging and (123)I-metaiodobenzylguanidine scintigraphy.

PubMed

Miyoshi, F; Ogawa, T; Kitao, S-i; Kitayama, M; Shinohara, Y; Takasugi, M; Fujii, S; Kaminou, T

2013-01-01

Progressive changes in the substantia nigra pars compacta and locus ceruleus of patients with Parkinson disease and Alzheimer disease visualized by neuromelanin MRI and cardiac postganglionic sympathetic nerve function on (123)I-metaiodobenzylguanidine scintigraphy have not been fully evaluated. We compared the diagnostic value of these modalities among patients with early Parkinson disease, late Parkinson disease, and Alzheimer disease. We compared contrast ratios of signal intensity in medial and lateral regions of the substantia nigra pars compacta and locus ceruleus with those of the tegmentum of the midbrain and the pons, respectively, by use of neuromelanin MRI in patients with early Parkinson disease (n = 13), late Parkinson disease (n = 31), Alzheimer disease (n = 6), and age-matched healthy control subjects (n = 20). We calculated heart-to-mediastinum ratios on (123)I-metaiodobenzylguanidine scintigrams after setting regions of interest on the left cardiac ventricle and upper mediastinum. The signal intensity of the lateral substantia nigra pars compacta on neuromelanin MRI was significantly reduced in early and late Parkinson disease, and that of the medial substantia nigra pars compacta was gradually and stage-dependently reduced in Parkinson disease. The signal intensity of the locus ceruleus was obviously reduced in late Parkinson disease. Signal reduction was not significant in the substantia nigra pars compacta and locus ceruleus of patients with Alzheimer disease. The heart-to-mediastinum ratio on (123)I-metaiodobenzylguanidine scintigrams was stage-dependently reduced in Parkinson disease and normal in Alzheimer disease. The signal intensity ratios in substantia nigra pars compacta and locus ceruleus on neuromelanin MRI positively correlated with the heart-to-mediastinum ratio on (123)I-metaiodobenzylguanidine scintigrams. Both neuromelanin MRI and (123)I-metaiodobenzylguanidine scintigraphy can help to evaluate disease progression in Parkinson

Acceptance of technology-based tools in a sample of Parkinson's patients.

PubMed

Duroseau, Nathalie; Abramson, Tobi; Pergament, Kathleen; Chan, Vivian; Govindavari, John Paul; Ciraco, Christina; Tegay, David; Krishnamachari, Bhuma

2017-03-01

Objectives Parkinson's disease is the second most common neurodegenerative movement disorder in the United States. Patients' opinions of technology-based tools for education and communication as related to Parkinson's disease are unclear with little documented research addressing the issue. The goal of this research was to investigate patient opinions about technology-based tools with a focus on differences between patients of different age groups. Methods A cross-sectional survey was used to assess views on using multiple different electronic methods for receiving instructions and communicating with healthcare providers in 109 Parkinson's disease patients. Results Approximately 28% (n = 28) of the subjects reported having unmet needs related to Parkinson's disease. Those 65 and over were less likely to believe that using technology to communicate with the healthcare center would result in themselves having a better understanding of their care (odds ratio = 0.36, 95% confidence interval: 0.14, 0.95). Those over 75 had a lower odds of being willing to use electronic methods (odds ratio = 0.33, 95% confidence interval: 0.14, 0.79), a lower odds of believing that technology would result in better self-understanding of medical needs (odds ratio = 0.27, 95% confidence interval: 0.12, 0.63) and a lower odds of believing that technology would result in their healthcare providers better understanding their needs (odds ratio = 0.32, 95% confidence interval: 0.14, 0.73). Discussion The results of this study indicate that older Parkinson's disease patients report a less favorable view regarding the role of technology in communicating with healthcare providers and for understanding their care.

Usefulness of quantitative susceptibility mapping for the diagnosis of Parkinson disease.

PubMed

Murakami, Y; Kakeda, S; Watanabe, K; Ueda, I; Ogasawara, A; Moriya, J; Ide, S; Futatsuya, K; Sato, T; Okada, K; Uozumi, T; Tsuji, S; Liu, T; Wang, Y; Korogi, Y

2015-06-01

Quantitative susceptibility mapping allows overcoming several nonlocal restrictions of susceptibility-weighted and phase imaging and enables quantification of magnetic susceptibility. We compared the diagnostic accuracy of quantitative susceptibility mapping and R2* (1/T2*) mapping to discriminate between patients with Parkinson disease and controls. For 21 patients with Parkinson disease and 21 age- and sex-matched controls, 2 radiologists measured the quantitative susceptibility mapping values and R2* values in 6 brain structures (the thalamus, putamen, caudate nucleus, pallidum, substantia nigra, and red nucleus). The quantitative susceptibility mapping values and R2* values of the substantia nigra were significantly higher in patients with Parkinson disease (P < .01); measurements in other brain regions did not differ significantly between patients and controls. For the discrimination of patients with Parkinson disease from controls, receiver operating characteristic analysis suggested that the optimal cutoff values for the substantia nigra, based on the Youden Index, were >0.210 for quantitative susceptibility mapping and >28.8 for R2*. The sensitivity, specificity, and accuracy of quantitative susceptibility mapping were 90% (19 of 21), 86% (18 of 21), and 88% (37 of 42), respectively; for R2* mapping, they were 81% (17 of 21), 52% (11 of 21), and 67% (28 of 42). Pair-wise comparisons showed that the areas under the receiver operating characteristic curves were significantly larger for quantitative susceptibility mapping than for R2* mapping (0.91 versus 0.69, P < .05). Quantitative susceptibility mapping showed higher diagnostic performance than R2* mapping for the discrimination between patients with Parkinson disease and controls. © 2015 by American Journal of Neuroradiology.

Lewy Body Dementias: Dementia With Lewy Bodies and Parkinson Disease Dementia

PubMed Central

Gomperts, Stephen N.

2016-01-01

ABSTRACT Purpose of Review: This article provides an overview of the clinical features, neuropathologic findings, diagnostic criteria, and management of dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD), together known as the Lewy body dementias. Recent Findings: DLB and PDD are common, clinically similar syndromes that share characteristic neuropathologic changes, including deposition of α-synuclein in Lewy bodies and neurites and loss of tegmental dopamine cell populations and basal forebrain cholinergic populations, often with a variable degree of coexisting Alzheimer pathology. The clinical constellations of DLB and PDD include progressive cognitive impairment associated with parkinsonism, visual hallucinations, and fluctuations of attention and wakefulness. Current clinical diagnostic criteria emphasize these features and also weigh evidence for dopamine cell loss measured with single-photon emission computed tomography (SPECT) imaging and for rapid eye movement (REM) sleep behavior disorder, a risk factor for the synucleinopathies. The timing of dementia relative to parkinsonism is the major clinical distinction between DLB and PDD, with dementia arising in the setting of well-established idiopathic Parkinson disease (after at least 1 year of motor symptoms) denoting PDD, while earlier cognitive impairment relative to parkinsonism denotes DLB. The distinction between these syndromes continues to be an active research question. Treatment for these illnesses remains symptomatic and relies on both pharmacologic and nonpharmacologic strategies. Summary: DLB and PDD are important and common dementia syndromes that overlap in their clinical features, neuropathology, and management. They are believed to exist on a spectrum of Lewy body disease, and some controversy persists in their differentiation. Given the need to optimize cognition, extrapyramidal function, and psychiatric health, management can be complex and should be systematic. PMID

Pharmacotherapy of Cardiovascular Autonomic Dysfunction in Parkinson Disease.

PubMed

Shibao, Cyndya A; Kaufmann, Horacio

2017-11-01

Cardiovascular autonomic dysfunctions, including neurogenic orthostatic hypotension, supine hypertension and post-prandial hypotension, are relatively common in patients with Parkinson disease. Recent evidence suggests that early autonomic impairment such as cardiac autonomic denervation and even neurogenic orthostatic hypotension occur prior to the appearance of the typical motor deficits associated with the disease. When neurogenic orthostatic hypotension develops, patients with Parkinson disease have an increased risk of mortality, falls, and trauma-related to falls. Neurogenic orthostatic hypotension reduces quality of life and contributes to cognitive decline and physical deconditioning. The co-existence of supine hypertension complicates the treatment of neurogenic orthostatic hypotension because it involves the use of drugs with opposing effects. Furthermore, treatment of neurogenic orthostatic hypotension is challenging because of few therapeutic options; in the past 20 years, the US Food and Drug Administration approved only two drugs for the treatment of this condition. Small, open-label or randomized studies using acute doses of different pharmacologic probes suggest benefit of other drugs as well, which could be used in individual patients under close monitoring. This review describes the pathophysiology of neurogenic orthostatic hypotension and supine hypertension in Parkinson disease. We discuss the mode of action and therapeutic efficacy of different pharmacologic agents used in the treatment of patients with cardiovascular autonomic failure.

Gastrointestinal dysfunction in idiopathic Parkinsonism: A narrative review

PubMed Central

Salari, Mehri; Fayyazi, Emad; Mirmosayyeb, Omid

2016-01-01

Currently, gastrointestinal (GI) dysfunctions in Parkinson's disease (PD) are well-recognized problems and are known to be the initial symptoms in the pathological process that eventually results in PD. Many types of PD-associated GI dysfunctions have been identified, including weight loss, nausea, hypersalivation, dysphagia, dyspepsia, abdominal pain, intestinal pseudo-obstruction, constipation, defecatory dysfunction, and small intestinal bacterial overgrowth. These symptoms can influence on other PD symptoms and are the second most significant predictor of the quality of life of these patients. Recognition of GI symptoms requires vigilance on the part of clinicians. Health-care providers should routinely ask direct questions about GI symptoms during office visits so that efforts can be directed at appropriate management of these distressing manifestations. Multiple system atrophy (MSA) and progressive supranuclear palsy are two forms of neurodegenerative Parkinsonism. Symptoms of autonomic dysfunctions such as GI dysfunction are common in patients with parkinsonian disorders. Despite recent progress in the recognition of GI dysfunctions, there are a few reviews on the management of GI dysfunction and GI symptoms in idiopathic Parkinsonism. In this review, the clinical presentation, pathophysiology, and treatment of each GI symptom in PD, MSA, and prostate-specific antigen will be discussed. PMID:28331512

Computational approaches to screen candidate ligands with anti- Parkinson's activity using R programming.

PubMed

Jayadeepa, R M; Niveditha, M S

2012-01-01

It is estimated that by 2050 over 100 million people will be affected by the Parkinson's disease (PD). We propose various computational approaches to screen suitable candidate ligand with anti-Parkinson's activity from phytochemicals. Five different types of dopamine receptors have been identified in the brain, D1-D5. Dopamine receptor D3 was selected as the target receptor. The D3 receptor exists in areas of the brain outside the basal ganglia, such as the limbic system, and thus may play a role in the cognitive and emotional changes noted in Parkinson's disease. A ligand library of 100 molecules with anti-Parkinson's activity was collected from literature survey. Nature is the best combinatorial chemist and possibly has answers to all diseases of mankind. Failure of some synthetic drugs and its side effects have prompted many researches to go back to ancient healing methods which use herbal medicines to give relief. Hence, the candidate ligands with anti-Parkinson's were selected from herbal sources through literature survey. Lipinski rules were applied to screen the suitable molecules for the study, the resulting 88 molecules were energy minimized, and subjected to docking using Autodock Vina. The top eleven molecules were screened according to the docking score generated by Autodock Vina Commercial drug Ropinirole was computed similarly and was compared with the 11 phytochemicals score, the screened molecules were subjected to toxicity analysis and to verify toxic property of phytochemicals. R Programming was applied to remove the bias from the top eleven molecules. Using cluster analysis and Confusion Matrix two phytochemicals were computationally selected namely Rosmarinic acid and Gingkolide A for further studies on the disease Parkinson's.

Traditional chinese medicine improves activities of daily living in Parkinson's disease.

PubMed

Pan, Weidong; Kwak, Shin; Liu, Yun; Sun, Yan; Fang, Zhenglong; Qin, Baofeng; Yamamoto, Yoshiharu

2011-01-01

We evaluated the effects of a traditional Chinese medicine (TCM), named Zeng-xiao An-shen Zhi-chan 2 (ZAZ2), on patients with Parkinson's disease (PD). Among 115 patients with idiopathic PD enrolled (mean age, 64.7 ± 10.2 years old), 110 patients (M = 65, F = 45; mean age, 64.9 ± 10.7 years old) completed the study. Patients took either ZAZ2 (n = 59) or placebo granule (n = 56) in a blind manner for 13 weeks while maintaining other anti-Parkinson medications unchanged. All participants wore a motion logger, and we analyzed the power-law temporal autocorrelation of the motion logger records taken on 3 occasions (before, one week, and 13 weeks after the drug administration). Drug efficacy was evaluated with the conventional Unified Parkinson Disease Rating Scale (UPDRS), as well as the power-law exponent α, which corresponds to the level of physical activity of the patients. ZAZ2 but not placebo granule improved the awake-sleep rhythm, the UPDRS Part II, Part II + III, and Part IV scores, and the α values. The results indicate that ZAZ2 improved activities of daily living (ADL) of parkinsonism and, thus, is a potentially suitable drug for long-term use.

Synthesis of walking sounds for alleviating gait disturbances in Parkinson's disease.

PubMed

Rodger, Matthew W M; Young, William R; Craig, Cathy M

2014-05-01

Managing gait disturbances in people with Parkinson's disease is a pressing challenge, as symptoms can contribute to injury and morbidity through an increased risk of falls. While drug-based interventions have limited efficacy in alleviating gait impairments, certain nonpharmacological methods, such as cueing, can also induce transient improvements to gait. The approach adopted here is to use computationally-generated sounds to help guide and improve walking actions. The first method described uses recordings of force data taken from the steps of a healthy adult which in turn were used to synthesize realistic gravel-footstep sounds that represented different spatio-temporal parameters of gait, such as step duration and step length. The second method described involves a novel method of sonifying, in real time, the swing phase of gait using real-time motion-capture data to control a sound synthesis engine. Both approaches explore how simple but rich auditory representations of action based events can be used by people with Parkinson's to guide and improve the quality of their walking, reducing the risk of falls and injury. Studies with Parkinson's disease patients are reported which show positive results for both techniques in reducing step length variability. Potential future directions for how these sound approaches can be used to manage gait disturbances in Parkinson's are also discussed.

Traditional Chinese Medicine Improves Activities of Daily Living in Parkinson's Disease

PubMed Central

Pan, Weidong; Kwak, Shin; Liu, Yun; Sun, Yan; Fang, Zhenglong; Qin, Baofeng; Yamamoto, Yoshiharu

2011-01-01

We evaluated the effects of a traditional Chinese medicine (TCM), named Zeng-xiao An-shen Zhi-chan 2 (ZAZ2), on patients with Parkinson's disease (PD). Among 115 patients with idiopathic PD enrolled (mean age, 64.7 ± 10.2 years old), 110 patients (M = 65, F = 45; mean age, 64.9 ± 10.7 years old) completed the study. Patients took either ZAZ2 (n = 59) or placebo granule (n = 56) in a blind manner for 13 weeks while maintaining other anti-Parkinson medications unchanged. All participants wore a motion logger, and we analyzed the power-law temporal autocorrelation of the motion logger records taken on 3 occasions (before, one week, and 13 weeks after the drug administration). Drug efficacy was evaluated with the conventional Unified Parkinson Disease Rating Scale (UPDRS), as well as the power-law exponent α, which corresponds to the level of physical activity of the patients. ZAZ2 but not placebo granule improved the awake-sleep rhythm, the UPDRS Part II, Part II + III, and Part IV scores, and the α values. The results indicate that ZAZ2 improved activities of daily living (ADL) of parkinsonism and, thus, is a potentially suitable drug for long-term use. PMID:21687764

Management of sleep disorders in Parkinson's disease and multiple system atrophy.

PubMed

Videnovic, Aleksandar

2017-05-01

Parkinson's disease (PD) and multiple system atrophy (MSA) are disorders associated with α synuclein-related neurodegeneration. Nonmotor symptoms are common hallmarks of these disorders, and disturbances of the sleep-wake cycle are among the most common nonmotor symptoms. It is only recently that sleep disturbances have received the attention of the medical and research community. Significant progress has been made in understanding the pathophysiology of sleep and wake disruption in alphasynucleinopathies during the past few decades. Despite these advancements, treatment options are limited and frequently associated with problematic side effects. Further studies that center on the development of novel treatment approaches are very much needed. In this article, the author discusses the current state of the management of disturbed sleep and alertness in PD and MSA. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Impaired anticipatory control of grasp during obstacle crossing in Parkinson's disease.

PubMed

McIsaac, Tara L; Diermayr, Gudrun; Albert, Frederic

2012-05-16

During self-paced walking, people with Parkinson's disease maintain anticipatory control during object grasping. However, common functional tasks often include carrying an object while changing step patterns mid-path and maneuvering over obstacles, increasing task complexity and attentional demands. Thus, the present study investigated the effect of Parkinson's disease on the modulation of grasping force changes as a function of gait-related inertial forces. Subjects with Parkinson's disease maintained the ability to scale and to couple over time their grip and inertial forces while walking at irregular step lengths, but were unable to maintain the temporal coupling of grasping forces compared to controls during obstacle crossing. We suggest that this deterioration in anticipatory control is associated with the increased demands of task complexity and attention during obstacle crossing. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Wireless Monitoring for Patients with Cardiovascular Diseases and Parkinson's Disease.

PubMed

Kefaliakos, Antonios; Pliakos, Ioannis; Charalampidou, Martha; Diomidous, Marianna

2016-01-01

The use of applications for mobile devices and wireless sensors is common for the sector of telemedicine. Recently various studies and systems were developed in order to help patients suffering from severe diseases such as cardiovascular diseases and Parkinson's disease. They present a challenge for the sector because such systems demand the flow of accurate data in real time and the use of specialized sensors. In this review will be presented some very interesting applications developed for patients with cardiovascular diseases and Parkinson's disease.

Repetitive Transcranial Magnetic Stimulation (rTMS) Therapy in Parkinson Disease: A Meta-Analysis.

PubMed

Wagle Shukla, Aparna; Shuster, Jonathan J; Chung, Jae Woo; Vaillancourt, David E; Patten, Carolynn; Ostrem, Jill; Okun, Michael S

2016-04-01

Several studies have reported repetitive transcranial magnetic stimulation (rTMS) therapy as an effective treatment for the control of motor symptoms in Parkinson disease. The objective of the study is to quantify the overall efficacy of this treatment. Systematic review and meta-analysis. We reviewed the literature on clinical rTMS trials in Parkinson disease since the technique was introduced in 1980. We used the following databases: MEDLINE, Web of Science, Cochrane, and CINAHL. Patients with Parkinson disease who were participating in prospective clinical trials that included an active arm and a control arm and change in motor scores on Unified Parkinson's Disease Rating Scale as the primary outcome. We pooled data from 21 studies that met these criteria. We then analyzed separately the effects of low- and high-frequency rTMS on clinical motor improvements. The overall pooled mean difference between treatment and control groups in the Unified Parkinson's Disease Rating Scale motor score was significant (4.0 points, 95% confidence interval, 1.5, 6.7; P = .005). rTMS therapy was effective when low-frequency stimulation (≤ 1 Hz) was used with a pooled mean difference of 3.3 points (95% confidence interval 1.6, 5.0; P = .005). There was a trend for significance when high-frequency stimulation (≥ 5 Hz) studies were evaluated with a pooled mean difference of 3.9 points (95% confidence interval, -0.7, 8.5; P = .08). rTMS therapy demonstrated benefits at short-term follow-up (immediately after a treatment protocol) with a pooled mean difference of 3.4 points (95% confidence interval, 0.3, 6.6; P = .03) as well as at long-term follow-up (average follow-up 6 weeks) with mean difference of 4.1 points (95% confidence interval, -0.15, 8.4; P = .05). There were insufficient data to statistically analyze the effects of rTMS when we specifically examined bradykinesia, gait, and levodopa-induced dyskinesia using quantitative methods. rTMS therapy in patients with Parkinson

Calcium Channel Antagonists as Disease-Modifying Therapy for Parkinson's Disease: Therapeutic Rationale and Current Status.

PubMed

Swart, Tara; Hurley, Michael J

2016-12-01

Parkinson's disease is a disabling hypokinetic neurological movement disorder in which the aetiology is unknown in the majority of cases. Current pharmacological treatments, though effective at restoring movement, are only symptomatic and do nothing to slow disease progression. Electrophysiological, epidemiological and neuropathological studies have implicated Ca V 1.3 subtype calcium channels in the pathogenesis of the disorder, and drugs with some selectivity for this ion channel (brain-penetrant dihydropyridine calcium channel blockers) are neuroprotective in animal models of the disease. Dihydropyridines have been safely used for decades to treat hypertension and other cardiovascular disorders. A phase II clinical trial found that isradipine was safely tolerated by patients with Parkinson's disease, and a phase III trial is currently underway to determine whether treatment with isradipine is neuroprotective and therefore able to slow the progression of Parkinson's disease. This manuscript reviews the current information about the use of dihydropyridines as therapy for Parkinson's disease and discusses the possible mechanism of action of these drugs, highlighting Ca V 1.3 calcium channels as a potential therapeutic target for neuroprotection in Parkinson's disease.

Cheaper, simpler, and better: tips for treating seniors with Parkinson disease.

PubMed

Ahlskog, J Eric

2011-12-01

Treatment of seniors with Parkinson disease is within the domain of primary care physicians and internists. A good working knowledge of carbidopa/levodopa principles should allow excellent care of most patients, at least during the early years of the disease. Even later, when levodopa responses become more complicated (eg, dyskinesias, motor fluctuations, insomnia, anxiety), levodopa adjustments may be all that is necessary. A dozen tips for optimizing treatment of Parkinson disease are discussed herein.

2006 World Parkinson Congress

DTIC Science & Technology

2006-03-01

treatments- 30 min. • Yoshikuni Mizuno ( Japan ) -- Pathology, environmental, epidemiology and genetics-30 min. 10:00 – 21:00 Art Exhibit...Young (USA) Chair) Venue 1:30 PM (25 min) Ted Dawson (USA) “The Syns of Parkinson’s Disease” 201 1:55 PM (25 min) Nobutaka Hattori ( Japan ...4:15 PM [Science] Genetic counseling in PD Tatiana Foroud (USA) Room 203B (60) (4)3:15-4:15 PM [Science] Is biologic surrogacy a reality

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. © 2015 International Parkinson and Movement Disorder Society.

Visual System Involvement in Patients with Newly Diagnosed Parkinson Disease.

PubMed

Arrigo, Alessandro; Calamuneri, Alessandro; Milardi, Demetrio; Mormina, Enricomaria; Rania, Laura; Postorino, Elisa; Marino, Silvia; Di Lorenzo, Giuseppe; Anastasi, Giuseppe Pio; Ghilardi, Maria Felice; Aragona, Pasquale; Quartarone, Angelo; Gaeta, Michele

2017-12-01

Purpose To assess intracranial visual system changes of newly diagnosed Parkinson disease in drug-naïve patients. Materials and Methods Twenty patients with newly diagnosed Parkinson disease and 20 age-matched control subjects were recruited. Magnetic resonance (MR) imaging (T1-weighted and diffusion-weighted imaging) was performed with a 3-T MR imager. White matter changes were assessed by exploring a white matter diffusion profile by means of diffusion-tensor imaging-based parameters and constrained spherical deconvolution-based connectivity analysis and by means of white matter voxel-based morphometry (VBM). Alterations in occipital gray matter were investigated by means of gray matter VBM. Morphologic analysis of the optic chiasm was based on manual measurement of regions of interest. Statistical testing included analysis of variance, t tests, and permutation tests. Results In the patients with Parkinson disease, significant alterations were found in optic radiation connectivity distribution, with decreased lateral geniculate nucleus V2 density (F, -8.28; P < .05), a significant increase in optic radiation mean diffusivity (F, 7.5; P = .014), and a significant reduction in white matter concentration. VBM analysis also showed a significant reduction in visual cortical volumes (P < .05). Moreover, the chiasmatic area and volume were significantly reduced (P < .05). Conclusion The findings show that visual system alterations can be detected in early stages of Parkinson disease and that the entire intracranial visual system can be involved. © RSNA, 2017 Online supplemental material is available for this article.

California’s Parkinson’s Disease Registry Pilot Project - Coordination Center and Northern California Ascertainment

DTIC Science & Technology

2014-03-01

www.capdregistry.org) and email box were created and launched in March, 2008. Requests for information about the registry from patients, colleagues and...d. Review and determination of study diagnosis. For cases with multiple parkinsonism codes (i.e. diagnosed with more than one of 332.0, 333.0...individuals (10.7%) had ICD-9 codes for other forms of neurodegenerative parkinsonism . The remaining 2.1% were primarily drug- induced parkinsonism

Emerging therapies for Parkinson's disease.

PubMed

Poewe, Werner; Mahlknecht, Philipp; Jankovic, Joseph

2012-08-01

The experimental therapeutics of Parkinson's disease are reviewed, highlighting the current pipeline of emerging therapeutic approaches. This review includes novel approaches to dopaminergic drug delivery such as intraintestinal infusions or new extended-release formulations of levodopa and also intrapulmonary delivery of apomorphine as well as novel dopaminergic agents like the monoamine oxidase-B inhibitor safinamide or novel catechol-O-methyl transferase inhibitors. An even greater number of ongoing clinical trials assess the efficacy and safety of nondopaminergic approaches to enhance motor control or reduce motor complications like fluctuations and dyskinesias. These include adenosine A2A antagonists, α-adrenergic and serotonergic agonists as well as drugs acting on the glutamatergic system. Gene-based or cell-based intrastriatal delivery of therapeutic principles that enhance striatal dopaminergic transmission directly or via the stimulation of trophic activity has also reached phase II clinical development with encouraging results in some studies. Finally, a wide spectrum of agents with a potential for slowing disease progression is currently tested. A variety of medical and nonmedical interventions in different phases of clinical development provide an interesting and promising portfolio of emerging therapies for Parkinson's disease.

A matter of motion or an emotional matter? Management of depression in Parkinson's disease.

PubMed

Lagopoulos, Jim; Malhi, Gin S; Ivanovski, Belinda; Cahill, Catherine M; Morris, John G L

2005-11-01

Depression is one of the most frequent comorbidities occurring in Parkinson's disease, affecting up to 50% of patients. Depression is associated with severe negative symptoms and has been shown to contribute to an increased rate of decline of both cognitive and motor function, profoundly impacting on the patient's quality of life. The symptoms of depression overlap with the motor features of Parkinson's disease, making detection difficult. Moreover, the lack of specialized screening tools means that depression remains undiagnosed and untreated in a high percentage of patients. However, depression in Parkinson's disease, when identified early, can be effectively treated with a variety of antidepressant medications, improving quality of life and preserving daily function. The focus of this review is to provide an overview of current knowledge regarding depression in Parkinson's disease, followed by a practical discussion addressing the issues of the detection, diagnosis and treatment.

Personality, depression, and premorbid lifestyle in twin pairs discordant for Parkinson's disease

PubMed Central

Heberlein, I.; Ludin, H.; Scholz, J.; Vieregge, P.

1998-01-01

Present personality traits (Freiburg personality inventory, FPI-R), depression (von Zerssen's depression scale), and self assessed state of health were evaluated in 15 twin pairs (six monozygotic and nine dizygotic; mean age 62.5 years) discordant for idiopathic Parkinson's disease and in 17 unrelated healthy control subjects. The twins had additional questionnaire based interviews on premorbid lifestyle.
For disability, twins with Parkinson's disease scored lower on FPI-R than controls in "achievement orientation" and "extraversion", higher in "inhibitedness", "somatic complaints", and "emotionality". They scored higher for depression and for state of health than unaffected twins and controls. For zygosity, monozygotic twins scored lower than dizygotic twins in "achievement orientation", "aggressiveness", and "strain". Monozygotic twins had less "achievement orientation" and "extraversion" and more "somatic complaints" than controls. Monozygotic twins had a lower within pair difference than dizygotic twins in "social orientation". During premorbid times the affected twin with later Parkinson's disease was estimated to have been "less often the leader" in the twin pair.
Although small in sample size, this twin study indicates a genetic impact for some personality features beyond the Parkinson's disease motor syndrome.

 PMID:9489545

Comparison of 3T and 7T susceptibility-weighted angiography of the substantia nigra in diagnosing Parkinson disease.

PubMed

Cosottini, M; Frosini, D; Pesaresi, I; Donatelli, G; Cecchi, P; Costagli, M; Biagi, L; Ceravolo, R; Bonuccelli, U; Tosetti, M

2015-03-01

Standard neuroimaging fails in defining the anatomy of the substantia nigra and has a marginal role in the diagnosis of Parkinson disease. Recently 7T MR target imaging of the substantia nigra has been useful in diagnosing Parkinson disease. We performed a comparative study to evaluate whether susceptibility-weighted angiography can diagnose Parkinson disease with a 3T scanner. Fourteen patients with Parkinson disease and 13 healthy subjects underwent MR imaging examination at 3T and 7T by using susceptibility-weighted angiography. Two expert blinded observers and 1 neuroradiology fellow evaluated the 3T and 7T images of the sample to identify substantia nigra abnormalities indicative of Parkinson disease. Diagnostic accuracy and intra- and interobserver agreement were calculated separately for 3T and 7T acquisitions. Susceptibility-weighted angiography 7T MR imaging can diagnose Parkinson disease with a mean sensitivity of 93%, specificity of 100%, and diagnostic accuracy of 96%. 3T MR imaging diagnosed Parkinson disease with a mean sensitivity of 79%, specificity of 94%, and diagnostic accuracy of 86%. Intraobserver and interobserver agreement was excellent at 7T. At 3T, intraobserver agreement was excellent for experts, and interobserver agreement ranged between good and excellent. The less expert reader obtained a diagnostic accuracy of 89% at 3T. Susceptibility-weighted angiography images obtained at 3T and 7T differentiate controls from patients with Parkinson disease with a higher diagnostic accuracy at 7T. The capability of 3T in diagnosing Parkinson disease might encourage its use in clinical practice. The use of the more accurate 7T should be supported by a dedicated cost-effectiveness study. © 2015 by American Journal of Neuroradiology.

Dorsal-to-Ventral Shift in Midbrain Dopaminergic Projections and Increased Thalamic/Raphe Serotonergic Function in Early Parkinson Disease.

PubMed

Joutsa, Juho; Johansson, Jarkko; Seppänen, Marko; Noponen, Tommi; Kaasinen, Valtteri

2015-07-01

Loss of nigrostriatal neurons leading to dopamine depletion in the dorsal striatum is the pathologic hallmark of Parkinson disease contributing to the primary motor symptoms of the disease. However, Parkinson pathology is more widespread in the brain, affecting also other dopaminergic pathways and neurotransmitter systems, but these changes are less well characterized. This study aimed to investigate the mesencephalic striatal and extrastriatal dopaminergic projections together with extrastriatal serotonin transporter binding in Parkinson disease. Two hundred sixteen patients with Parkinson disease and 204 control patients (patients without neurodegenerative parkinsonism syndromes and normal SPECT imaging) were investigated with SPECT using the dopamine/serotonin transporter ligand (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ((123)I-FP-CIT) in the clinical setting. The group differences and midbrain correlations were analyzed voxel by voxel over the entire brain. We found that Parkinson patients had lower (123)I-FP-CIT uptake in the striatum and ventral midbrain but higher uptake in the thalamus and raphe nuclei than control patients. In patients with Parkinson disease, the correlation of the midbrain tracer uptake was shifted from the putamen to widespread corticolimbic areas. All findings were highly significant at the voxel level familywise error-corrected P value of less than 0.05. Our findings show that Parkinson disease is associated not only with the degeneration of the nigrostriatal dopamine neurotransmission, but also with a parallel shift toward mesolimbic and mesocortical function. Furthermore, Parkinson disease patients seem to have upregulation of brain serotonin transporter function at the early phase of the disease. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Current Experimental Studies of Gene Therapy in Parkinson's Disease

PubMed Central

Lin, Jing-ya; Xie, Cheng-long; Zhang, Su-fang; Yuan, Weien; Liu, Zhen-Guo

2017-01-01

Parkinson's disease (PD) was characterized by late-onset, progressive dopamine neuron loss and movement disorders. The progresses of PD affected the neural function and integrity. To date, most researches had largely addressed the dopamine replacement therapies, but the appearance of L-dopa-induced dyskinesia hampered the use of the drug. And the mechanism of PD is so complicated that it's hard to solve the problem by just add drugs. Researchers began to focus on the genetic underpinnings of Parkinson's disease, searching for new method that may affect the neurodegeneration processes in it. In this paper, we reviewed current delivery methods used in gene therapies for PD, we also summarized the primary target of the gene therapy in the treatment of PD, such like neurotrophic factor (for regeneration), the synthesis of neurotransmitter (for prolong the duration of L-dopa), and the potential proteins that might be a target to modulate via gene therapy. Finally, we discussed RNA interference therapies used in Parkinson's disease, it might act as a new class of drug. We mainly focus on the efficiency and tooling features of different gene therapies in the treatment of PD. PMID:28515689

Loudness perception and speech intensity control in Parkinson's disease.

PubMed

Clark, Jenna P; Adams, Scott G; Dykstra, Allyson D; Moodie, Shane; Jog, Mandar

2014-01-01

The aim of this study was to examine loudness perception in individuals with hypophonia and Parkinson's disease. The participants included 17 individuals with hypophonia related to Parkinson's disease (PD) and 25 age-equivalent controls. The three loudness perception tasks included a magnitude estimation procedure involving a sentence spoken at 60, 65, 70, 75 and 80 dB SPL, an imitation task involving a sentence spoken at 60, 65, 70, 75 and 80 dB SPL, and a magnitude production procedure involving the production of a sentence at five different loudness levels (habitual, two and four times louder and two and four times quieter). The participants with PD produced a significantly different pattern and used a more restricted range than the controls in their perception of speech loudness, imitation of speech intensity, and self-generated estimates of speech loudness. The results support a speech loudness perception deficit in PD involving an abnormal perception of externally generated and self-generated speech intensity. Readers will recognize that individuals with hypophonia related to Parkinson's disease may demonstrate a speech loudness perception deficit involving the abnormal perception of externally generated and self-generated speech intensity. Copyright © 2014 Elsevier Inc. All rights reserved.

Environmental risk factors and Parkinson's disease: An umbrella review of meta-analyses.

PubMed

Bellou, Vanesa; Belbasis, Lazaros; Tzoulaki, Ioanna; Evangelou, Evangelos; Ioannidis, John P A

2016-02-01

Parkinson's disease is a neurological disorder with complex pathogenesis implicating both environmental and genetic factors. We aimed to summarise the environmental risk factors that have been studied for potential association with Parkinson's disease, assess the presence of diverse biases, and identify the risk factors with the strongest support. We searched PubMed from inception to September 18, 2015, to identify systematic reviews and meta-analyses of observational studies that examined associations between environmental factors and Parkinson's disease. For each meta-analysis we estimated the summary effect size by random-effects and fixed-effects models, the 95% confidence interval and the 95% prediction interval. We estimated the between-study heterogeneity expressed by I(2), evidence of small-study effects and evidence of excess significance bias. Overall, 75 unique meta-analyses on different risk factors for Parkinson's disease were examined, covering diverse biomarkers, dietary factors, drugs, medical history or comorbid diseases, exposure to toxic environmental agents and habits. 21 of 75 meta-analyses had results that were significant at p < 0.001 by random-effects. Evidence for an association was convincing (more than 1000 cases, p < 10(-6) by random-effects, not large heterogeneity, 95% prediction interval excluding the null value and absence of hints for small-study effects and excess significance bias) for constipation, and physical activity. Many environmental factors have substantial evidence of association with Parkinson's disease, but several, perhaps most, of them may reflect reverse causation, residual confounding, information bias, sponsor conflicts or other caveats. Copyright © 2016. Published by Elsevier Ltd.

The effect of surface electrical stimulation on swallowing in dysphagic Parkinson patients.

PubMed

Baijens, Laura W J; Speyer, Renée; Passos, Valeria Lima; Pilz, Walmari; Roodenburg, Nel; Clavé, Père

2012-12-01

Surface electrical stimulation has been applied on a large scale to treat oropharyngeal dysphagia. Patients suffering from oropharyngeal dysphagia in the presence of Parkinson's disease have been treated with surface electrical stimulation. Because of controversial reports on this treatment, a pilot study was set up. This study describes the effects of a single session of surface electrical stimulation using different electrode positions in ten patients with idiopathic Parkinson's disease (median Hoehn and Yahr score: II) and oropharyngeal dysphagia compared to ten age- and gender-matched healthy control subjects during videofluoroscopy of swallowing. Three different electrode positions were applied in random order per subject. For each electrode position, the electrical current was respectively turned "on" and "off" in random order. Temporal, spatial, and visuoperceptual variables were scored by experienced raters who were blinded to the group, electrode position, and status (on/off) of the electrical current. Interrater and interrater reliabilities were calculated. Only a few significant effects of a single session of surface electrical stimulation using different electrode positions in dysphagic Parkinson patients could be observed in this study. Furthermore, significant results for temporal and spatial variables were found regardless of the status of the electrical current in both groups suggesting placebo effects. Following adjustment for electrical current status as well as electrode positions (both not significant, P > 0.05) in the statistical model, significant group differences between Parkinson patients and healthy control subjects emerged. Further studies are necessary to evaluate the potential therapeutic effect and mechanism of electrical stimulation in dysphagic patients with Parkinson's disease.

Dopamine agonists in the treatment of Parkinson's disease.

PubMed

Bonuccelli, Ubaldo; Pavese, Nicola

2006-01-01

Dopamine agonists are highly effective as adjunctive therapy to levodopa in advanced Parkinson's disease and have rapidly gained popularity as a monotherapy in the early stages of Parkinson's disease for patients less than 65-70 years old. In the latter case, dopamine agonists are about as effective as levodopa but patients demonstrate a lower tendency to develop motor complications. However, dopamine agonists lose efficacy over time and the number of patients remaining on agonist monotherapy decreases to less than 50% after 3 years of treatment. Thus, after a few years of treatment the majority of patients who started on dopamine agonists will be administered levodopa, in a combined dopaminergic therapy, in order to achieve a better control of motor symptoms.

Cheaper, Simpler, and Better: Tips for Treating Seniors With Parkinson Disease

PubMed Central

Ahlskog, J. Eric

2011-01-01

Treatment of seniors with Parkinson disease is within the domain of primary care physicians and internists. A good working knowledge of carbidopa/levodopa principles should allow excellent care of most patients, at least during the early years of the disease. Even later, when levodopa responses become more complicated (eg, dyskinesias, motor fluctuations, insomnia, anxiety), levodopa adjustments may be all that is necessary. A dozen tips for optimizing treatment of Parkinson disease are discussed herein. PMID:22134940

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

PubMed

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

2014-07-01

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). 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. 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. 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.

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of In Silico Anti-parkinson potential of β-asarone.

PubMed

Gupta, Meenakshi; Kant, Kamal; Sharma, Ruchika; Kumar, Anoop

2018-04-16

Parkinson's disease is affecting millions of people worldwide. The prevalence of Parkinson's disease is 0.3% globally, rising to 1% in more than 60 years of age and 4% in more than 80 years of age and the figures are thought to be doubled by 2030. Thus, there is a great need to identify novel therapeutic strategies or candidate drug molecule which can rescue neuronal degeneration. β-asarone has potential to act as a neuroprotective agent but regarding its role in Parkinson disease, very few reports are available. Thus, this study was undertaken to unlock the potential of β-asarone against Parkinson's disease. The Absorption, Distribution, Metabolism, and Excretion (ADME) analysis has been done by using Swiss ADME Predictor. The interactions of β-asarone towards dopaminergic receptors were investigated by Glide Program 5.0. The crystal structures of dopamine receptors were retrieved from Research Collaboratory for Structural Bioinformatics- Protein Data Bank (RCSB-PDB). The structure of β-asarone was drawn in Chem Draw Ultra 7.0.1. Finally, the toxicity of β-asarone has been predicted by using online web-servers like Lazar and Protox. The ADME data of current investigation has shown good oral bioavailability of β-asarone. It also showed a good binding affinity towards dopaminergic receptors. Further, it was found to be interacting through hydrogen bond with different amino acid residues of D2 and D3 receptors. However, β-asarone was predicted to be toxic in various species of rodents, as per the results of toxicity online web servers. Based on the current finding from ADME and docking studies, these preliminary results may act as effective precursor tool for development of β-asarone as a promising anti-Parkinson agent. However, furthermore experimental validation using in-vitro & in-vivo studies is needed to explore their therapeutic & toxic effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Improved nutritional status is related to improved quality of life in Parkinson's disease.

PubMed

Sheard, Jamie M; Ash, Susan; Mellick, George D; Silburn, Peter A; Kerr, Graham K

2014-11-18

Quality of life is poorer in Parkinson's disease than in other conditions and in the general population without Parkinson's disease. Malnutrition also results in poorer quality of life. This study aimed at determining the relationship between quality of life and nutritional status. Community-dwelling people with Parkinson's disease >18 years old were recruited. The Patient-Generated Subjective Global Assessment (PG-SGA) assessed nutritional status. The Parkinson's Disease Questionnaire 39 (PDQ-39) measured quality of life. Phase I was cross-sectional. The malnourished in Phase I were eligible for a nutrition intervention phase, randomised into 2 groups: standard care (SC) with provision of nutrition education materials only and intervention (INT) with individualised dietetic advice and regular weekly follow-up. Data were collected at baseline, 6 weeks, and 12 weeks. Phase I consisted of 120 people who completed the PDQ-39. Phase II consisted of 9 in the SC group and 10 in the INT group. In Phase I, quality of life was poorer in the malnourished, particularly for mobility and activities of daily living domains. There was a significant correlation between PG-SGA and PDQ-39 scores (Phase I, rs = 0.445, p = .000; Phase II, rs = .426, p = .002). In Phase II, no significant difference in the PDQ-39 total or sub-scores was observed between the INT and SC groups; however, there was significant improvement in the emotional well-being domain for the entire group, X2(2) = 8.84, p = .012. Malnourished people with Parkinson's disease had poorer quality of life than the well-nourished, and improvements in nutritional status resulted in quality of life improvements. Attention to nutritional status is an important component of quality of life and therefore the total care of people with Parkinson's disease. ACTRN12610000819022.

Glaucoma correlates with increased risk of Parkinson's disease in the elderly: a national-based cohort study in Taiwan.

PubMed

Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu

2017-08-01

Very little is known about the association between glaucoma and Parkinson's disease in the elderly. The objective of this study was to determine whether glaucoma is associated with Parkinson's disease in older people in Taiwan. A retrospective cohort study was conducted to analyze the Taiwan National Health Insurance Program database from 2000 to 2010. We included 4330 subjects aged 65 years or older with newly diagnosed glaucoma as the glaucoma group, and 17,000 randomly selected subjects without a glaucoma diagnosis as the non-glaucoma group. Both groups were matched for sex, age, other comorbidities, and index year of glaucoma diagnosis. The incidence of Parkinson's disease at the end of 2011 was measured. A multivariable Cox proportional hazard regression model was used to measure the hazard ratio and 95% confidence intervals for Parkinson's disease associated with glaucoma. The overall incidence of Parkinson's disease was 1.28-fold higher in the glaucoma group than that in the non-glaucoma group (7.73 vs. 6.02 per 1000 person-years; 95% confidence interval 1.18, 1.40). After controlling for potential confounding factors, the adjusted hazard ratio of Parkinson's disease was 1.23 for the glaucoma group (95% confidence interval 1.05, 1.46), compared with the non-glaucoma group. Older people with glaucoma correlate with a small but statistically significant increase in the risk for Parkinson's disease. Whether glaucoma may be a non-motor feature of Parkinson's disease in older people requires further research to confirm.

Improving community healthcare for patients with Parkinson's disease: the dutch model.

PubMed

Keus, S H J; Oude Nijhuis, L B; Nijkrake, M J; Bloem, B R; Munneke, M

2012-01-01

Because of the complex nature of Parkinson's disease, a wide variety of health professionals are involved in care. Stepwise, we have addressed the challenges in the provision of multidisciplinary care for this patient group. As a starting point, we have gained detailed insight into the current delivery of allied healthcare, as well as the barriers and facilitators for optimal care. To overcome the identified barriers, a tertiary referral centre was founded; evidence-based guidelines were developed and cost-effectively implemented within regional community networks of specifically trained allied health professionals (the ParkinsonNet concept). We increasingly use ICT to bind these professional networks together and also to empower and engage patients in making decisions about their health. This comprehensive approach is likely to be feasible for other countries as well, so we currently collaborate in a European collaboration to improve community care for persons with Parkinson's disease.

Vocal symptoms in Parkinson disease treated with levodopa. A case report.

PubMed

Schley, W S; Fenton, E; Niimi, S

1982-01-01

This is a report of a patient with unusually severe hoarseness in the absence of vocal fold pathology demonstrating Parkinson disease as one of the neurological diseases in which vocal symptoms occur. Although it is classifiably a severe, progressive, degenerative disorder, the popularity of pharmacotherapy for Parkinson disease during the past decade has resulted in improved functionality for an undetermined course of time in most patients. The classically described deterioration of speech ad voice may develop in a variant manner difficult to distinguish as disease-related, as this case report illustrates. An explanation of the hoarseness based on dyssynchronous vocal fold motion related to the disease is suggested by the acoustic methods (spectrography, waveform analysis) used in this study, and supported by strobe light laryngoscopy. This conclusion is important because of the extremely high incidences of varying degrees of hoarseness reported in recent studies of Parkinson disease.

Expressive Behavior in Parkinson's Disease as a Function of Interview Context

PubMed Central

Takahashi, Kayoko; Tickle-Degnen, Linda; Coster, Wendy J.; Latham, Nancy K.

2010-01-01

OBJECTIVE Parkinson's disease affects the ability to express motivation through face, body, and voice; contextual factors may facilitate or inhibit expressive behavior. The purpose of this study was to determine whether qualities of the interview context are associated with client motivational behavior in Parkinson's disease. METHOD Men and women with Parkinson's disease (N = 106) discussed 2 topics (enjoyable activity vs. frustrating activity) during an assessment with a female or male interviewer. From videotaped clips, displays of 4 categories of motivation and 12 verbal and 18 nonverbal behavioral patterns were rated. RESULTS During the discussion of enjoyable activities, participants used more positive words, smiled more, and were more facially expressive. Participants were less talkative about their negative feelings and appeared to be more apathetic with the same-gender interviewer. CONCLUSION Occupational therapy practitioners should vary the emotional tone of their questions to improve the validity of motivation assessments. PMID:20608279

Three-dimensional evaluation of postural stability in Parkinson's disease with mobile technology.

PubMed

Ozinga, Sarah J; Koop, Mandy Miller; Linder, Susan M; Machado, Andre G; Dey, Tanujit; Alberts, Jay L

2017-01-01

Postural instability is a hallmark of Parkinson's disease. Objective metrics to characterize postural stability are necessary for the development of treatment algorithms to aid in the clinical setting. The aim of this project was to validate a mobile device platform and resultant three-dimensional balance metric that characterizes postural stability. A mobile Application was developed, in which biomechanical data from inertial sensors within a mobile device were processed to characterize movement of center of mass in the medial-lateral, anterior-posterior and trunk rotation directions. Twenty-seven individuals with Parkinson's disease and 27 age-matched controls completed various balance tasks. A postural stability metric quantifying the amplitude (peak-to-peak) of sway acceleration in each movement direction was compared between groups. The peak-to-peak value in each direction for each individual with Parkinson's disease across all trials was expressed as a normalized value of the control data to identify individuals with severe postural instability, termed Cleveland Clinic-Postural Stability Index. In all conditions, the balance metric for peak-to-peak was significantly greater in Parkinson's disease compared to controls (p < 0.01 for all tests). The balance metric, in conjunction with mobile device sensors, provides a rapid and systematic metric for quantifying postural stability in Parkinson's disease.

Identification of candidate cerebrospinal fluid biomarkers in parkinsonism using quantitative proteomics.

PubMed

Magdalinou, N K; Noyce, A J; Pinto, R; Lindstrom, E; Holmén-Larsson, J; Holtta, M; Blennow, K; Morris, H R; Skillbäck, T; Warner, T T; Lees, A J; Pike, I; Ward, M; Zetterberg, H; Gobom, J

2017-04-01

Neurodegenerative parkinsonian syndromes have significant clinical and pathological overlap, making early diagnosis difficult. Cerebrospinal fluid (CSF) biomarkers may aid the differentiation of these disorders, but other than α-synuclein and neurofilament light chain protein, which have limited diagnostic power, specific protein biomarkers remain elusive. To study disease mechanisms and identify possible CSF diagnostic biomarkers through discovery proteomics, which discriminate parkinsonian syndromes from healthy controls. CSF was collected consecutively from 134 participants; Parkinson's disease (n = 26), atypical parkinsonian syndromes (n = 78, including progressive supranuclear palsy (n = 36), multiple system atrophy (n = 28), corticobasal syndrome (n = 14)), and elderly healthy controls (n = 30). Participants were divided into a discovery and a validation set for analysis. The samples were subjected to tryptic digestion, followed by liquid chromatography-mass spectrometry analysis for identification and relative quantification by isobaric labelling. Candidate protein biomarkers were identified based on the relative abundances of the identified tryptic peptides. Their predictive performance was evaluated by analysis of the validation set. 79 tryptic peptides, derived from 26 proteins were found to differ significantly between atypical parkinsonism patients and controls. They included acute phase/inflammatory markers and neuronal/synaptic markers, which were respectively increased or decreased in atypical parkinsonism, while their levels in PD subjects were intermediate between controls and atypical parkinsonism. Using an unbiased proteomic approach, proteins were identified that were able to differentiate atypical parkinsonian syndrome patients from healthy controls. Our study indicates that markers that may reflect neuronal function and/or plasticity, such as the amyloid precursor protein, and inflammatory markers may hold future promise as

A Parkinson's disease measurement system using laser lines and a CMOS image sensor.

PubMed

Chang, Rong-Seng; Chiu, Jen-Hwey; Chen, Fang-Pey; Chen, Jyh-Cheng; Yang, Jen-Lin

2011-01-01

This paper presents a non-invasive, non-contact system for the measurement of the arterial dorsum manus vibration waveforms of Parkinson disease patients. The laser line method is applied to detect the dorsum manus vibration in rest and postural situations. The proposed measurement system mainly consists of a laser diode and a low cost complementary metal-oxide semiconductor (CMOS) image sensor. Laser line and centroid methods are combined with the Fast Fourier Transform (FFT) in this study. The shape and frequency and relative frequency of the dorsum manus vibration waveforms can be detected rapidly using our Parkinson's disease measurement system. A laser line near the wrist joint is used as the testing line. The experimental results show an obvious increase in the amplitude and frequency of dorsum manus variation in the measured region in patients suffering from Parkinson's disease, indicating the obvious effects of the disease. Both in postural and rest state measurements, as the patient disease age increases the vibration frequency increases. The measurement system is well suited for evaluating and pre-diagnosing early stage Parkinson's disease.

Drug-induced parkinsonism following chronic methamphetamine use by a patient on haloperidol decanoate.

PubMed

Matthew, Binoj J; Gedzior, Joanna S

2015-01-01

This report attempts to highlight that use of an antipsychotic and concurrent chronic use of methamphetamine can cause drug-induced parkinsonism. Methamphetamine is usually not encountered in the list of agents that induce drug-induced parkinsonism and so its consideration particularly during chronic use by a patient who is also on an antipsychotic is worthwhile because of its popularity as an illegal narcotic. This case report describes just such a case of drug-induced parkinsonism which is a subacute syndrome that mimics Parkinson's disease. Although less alarming than dystonia, it is more common, more difficult to treat and can be the cause of significant disability during maintenance treatment especially in the elderly. In most cases, symptoms are reversible in days or weeks, but occasionally, especially in the elderly, or if long-acting injectable antipsychotics are used-as in this case-symptoms may last for weeks or months. The report also illustrates the neuronal workings due to chronic methamphetamine-use and the additive effects of dopamine blockade by antipsychotics such as haloperidol. © The Author(s) 2015.

Validity of Montreal Cognitive Assessment in non-english speaking patients with Parkinson's disease.

PubMed

Krishnan, Syam; Justus, Sunitha; Meluveettil, Radhamani; Menon, Ramshekhar N; Sarma, Sankara P; Kishore, Asha

2015-01-01

The Montreal Cognitive Assessment is a brief and easy screening tool for accurately testing cognitive dysfunction in Parkinson's disease. We tested its validity for use in non-English (Malayalam) speaking patients with Parkinson's disease. We developed a Malayalam (a south-Indian language) version of Montreal Cognitive Assessment and applied to 70 patients with Parkinson's disease and 60 age- and education-matched healthy controls. Metric properties were assessed, and the scores were compared with the performance in validated Malayalam versions of Mini Mental Status Examination and Addenbrooke's Cognitive Examination. The Montreal Cognitive Assessment-Malayalam showed good internal consistency and test-retest reliability and its scores correlated with Mini Mental Status Examination (patients: R = 0.70; P < 0.001; healthy controls: R = 0.26; P = 0.04) and Addenbrooke's Cognitive Examination (patients: R = 0.8; P < 0.001; healthy controls: R = 0.52; P < 0.001) scores. This study establishes the reliability of cross-cultural adaptation of Montreal Cognitive Assessment for assessing cognition in Malayalam-speaking Parkinson's disease patients for early screening and potential future interventions for cognitive dysfunction.

Hearing loss may be a non-motor feature of Parkinson's disease in older people in Taiwan.

PubMed

Lai, S-W; Liao, K-F; Lin, C-L; Lin, C-C; Sung, F-C

2014-05-01

The aim of this study was to explore whether hearing loss is associated with the risk of Parkinson's disease in the elderly in Taiwan. Using claims data of the Taiwan National Health Insurance Program, 4976 patients (aged 65 years or older) with newly diagnosed hearing loss from 2000 to 2010 were identified and 19 904 subjects without hearing loss were randomly selected as comparisons, frequency matched by sex, age and index year of diagnosing hearing loss. The incidence of Parkinson's disease by the end of 2010 and the associated risk factors were investigated. The incidence of Parkinson's disease in the hearing loss group was 1.77-fold higher than that in the non-hearing-loss group (3.11 vs. 1.76 per 1000 person-years). After controlling for confounding factors, the adjusted hazard ratio (HR) of Parkinson's disease was 1.53 (95% CI 1.17, 1.99) for the hearing loss group compared with the non-hearing-loss group. Male sex (HR = 1.33, 95% CI 1.02, 1.74), age (for each year, HR = 1.06, 95% CI 1.04, 1.09), hypertension (HR = 1.70, 95% CI 1.26, 2.30) and cerebrovascular disease (HR = 1.78, 95% CI 1.37, 2.32) were also significantly associated with the risk of Parkinson's disease. Hearing loss correlates with an increased risk of Parkinson's disease in the elderly. Further studies are needed to confirm whether hearing loss could be a non-motor feature of Parkinson's disease. © 2014 The Author(s) European Journal of Neurology © 2014 EFNS.

A Systematic Review and Meta-Analysis of Strength Training in Individuals With Multiple Sclerosis Or Parkinson Disease

PubMed Central

Cruickshank, Travis M.; Reyes, Alvaro R.; Ziman, Melanie R.

2015-01-01

Abstract Strength training has, in recent years, been shown to be beneficial for people with Parkinson disease and multiple sclerosis. Consensus regarding its utility for these disorders nevertheless remains contentious among healthcare professionals. Greater clarity is required, especially in regards to the type and magnitude of effects as well as the response differences to strength training between individuals with Parkinson disease or multiple sclerosis. This study examines the effects, magnitude of those effects, and response differences to strength training between patients with Parkinson disease or multiple sclerosis. A comprehensive search of electronic databases including Physiotherapy Evidence Database scale, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL was conducted from inception to July 2014. English articles investigating the effect of strength training for individuals with neurodegenerative disorders were selected. Strength training trials that met the inclusion criteria were found for individuals with Parkinson disease or multiple sclerosis. Individuals with Parkinson disease or multiple sclerosis were included in the study. Strength training interventions included traditional (free weights/machine exercises) and nontraditional programs (eccentric cycling). Included articles were critically appraised using the Physiotherapy Evidence Database scale. Of the 507 articles retrieved, only 20 articles met the inclusion criteria. Of these, 14 were randomized and 6 were nonrandomized controlled articles in Parkinson disease or multiple sclerosis. Six randomized and 2 nonrandomized controlled articles originated from 3 trials and were subsequently pooled for systematic analysis. Strength training was found to significantly improve muscle strength in people with Parkinson disease (15%–83.2%) and multiple sclerosis (4.5%–36%). Significant improvements in mobility (11.4%) and disease progression were also reported in people

A systematic review and meta-analysis of strength training in individuals with multiple sclerosis or Parkinson disease.

PubMed

Cruickshank, Travis M; Reyes, Alvaro R; Ziman, Melanie R

2015-01-01

Strength training has, in recent years, been shown to be beneficial for people with Parkinson disease and multiple sclerosis. Consensus regarding its utility for these disorders nevertheless remains contentious among healthcare professionals. Greater clarity is required, especially in regards to the type and magnitude of effects as well as the response differences to strength training between individuals with Parkinson disease or multiple sclerosis. This study examines the effects, magnitude of those effects, and response differences to strength training between patients with Parkinson disease or multiple sclerosis. A comprehensive search of electronic databases including Physiotherapy Evidence Database scale, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL was conducted from inception to July 2014. English articles investigating the effect of strength training for individuals with neurodegenerative disorders were selected. Strength training trials that met the inclusion criteria were found for individuals with Parkinson disease or multiple sclerosis. Individuals with Parkinson disease or multiple sclerosis were included in the study. Strength training interventions included traditional (free weights/machine exercises) and nontraditional programs (eccentric cycling). Included articles were critically appraised using the Physiotherapy Evidence Database scale. Of the 507 articles retrieved, only 20 articles met the inclusion criteria. Of these, 14 were randomized and 6 were nonrandomized controlled articles in Parkinson disease or multiple sclerosis. Six randomized and 2 nonrandomized controlled articles originated from 3 trials and were subsequently pooled for systematic analysis. Strength training was found to significantly improve muscle strength in people with Parkinson disease (15%-83.2%) and multiple sclerosis (4.5%-36%). Significant improvements in mobility (11.4%) and disease progression were also reported in people with Parkinson

The Experience of Parkinson's Disease: A Systematic Review and Meta-Ethnography

PubMed Central

Soundy, Andrew

2014-01-01

There has been little attempt to summarise and synthesise qualitative studies concerning the experience and perception of living with Parkinson's disease. Bringing this information together would provide a background to understand the importance of an individual's social identity on their well-being and hope. Three primary aims were identified (a) understanding the importance of social identity and meaningful activities on individuals' well-being, (b) identifying factors and strategies that influence well-being and hope, and (c) establishing a model that relates to an individual's hope and well-being. Three stages were undertaken including a traditional electronic search, a critical appraisal of articles, and a synthesis of studies. Qualitative articles were included that considered the experience of living with Parkinson's disease. Thirty seven articles were located and included in the review. Five themes were identified and the themes were used to inform development of a new model of hope enablement. The current review furthered understanding of how physical symptoms and the experience of Parkinson's disease affect the individual's well-being and hope. Social identity was established as a key factor that influenced an individual's well-being. Being able to maintain, retain, or develop social identities was essential for the well-being and hope of individuals with Parkinson's disease. Understanding the factors which prevent or can facilitate this is essential. PMID:25525623

Relative Mortality in U.S. Medicare Beneficiaries with Parkinson Disease and Hip and Pelvic Fractures

PubMed Central

Harris-Hayes, Marcie; Willis, Allison W.; Klein, Sandra E.; Czuppon, Sylvia; Crowner, Beth; Racette, Brad A.

2014-01-01

Background: Parkinson disease is a neurodegenerative disease that affects gait and postural stability, resulting in an increased risk of falling. The purpose of this study was to estimate mortality associated with demographic factors after hip or pelvic (hip/pelvic) fracture in people with Parkinson disease. A secondary goal was to compare the mortality associated with Parkinson disease to that associated with other common medical conditions in patients with hip/pelvic fracture. Methods: This was a retrospective observational cohort study of 1,980,401 elderly Medicare beneficiaries diagnosed with hip/pelvic fracture from 2000 to 2005 who were identified with use of the Beneficiary Annual Summary File. The race/ethnicity distribution of the sample was white (93.2%), black (3.8%), Hispanic (1.2%), and Asian (0.6%). Individuals with Parkinson disease (131,215) were identified with use of outpatient and carrier claims. Cox proportional hazards models were used to estimate the risk of death associated with demographic and clinical variables and to compare mortality after hip/pelvic fracture between patients with Parkinson disease and those with other medical conditions associated with high mortality after hip/pelvic fracture, after adjustment for race/ethnicity, sex, age, and modified Charlson comorbidity score. Results: Among those with Parkinson disease, women had lower mortality after hip/pelvic fracture than men (adjusted hazard ratio [HR] = 0.63, 95% confidence interval [CI]) = 0.62 to 0.64), after adjustment for covariates. Compared with whites, blacks had a higher (HR = 1.12, 95% CI = 1.09 to 1.16) and Hispanics had a lower (HR = 0.87, 95% CI = 0.81 to 0.95) mortality, after adjustment for covariates. Overall, the adjusted mortality rate after hip/pelvic fracture in individuals with Parkinson disease (HR = 2.41, 95% CI = 2.37 to 2.46) was substantially elevated compared with those without the disease, a finding similar to the increased mortality associated with a

Identification of Balance Deficits in People with Parkinson Disease; is the Sensory Organization Test Enough?

PubMed

Gera, G; Freeman, D L; Blackinton, M T; Horak, F B; King, L

2016-02-01

Balance deficits in people with Parkinson's disease can affect any of the multiple systems encompassing balance control. Thus, identification of the specific deficit is crucial in customizing balance rehabilitation. The sensory organization test, a test of sensory integration for balance control, is sometimes used in isolation to identify balance deficits in people with Parkinson's disease. More recently, the Mini-Balance Evaluations Systems Test, a clinical scale that tests multiple domains of balance control, has begun to be used to assess balance in patients with Parkinson's disease. The purpose of our study was to compare the use of Sensory Organization Test and Mini-Balance Evaluations Systems Test in identifying balance deficits in people with Parkinson's disease. 45 participants (27M, 18F; 65.2 ± 8.2 years) with idiopathic Parkinson's disease participated in the cross-sectional study. Balance assessment was performed using the Sensory Organization Test and the Mini-Balance Evaluations Systems Test. People were classified into normal and abnormal balance based on the established cutoff scores (normal balance: Sensory Organization Test >69; Mini-Balance Evaluations Systems Test >73). More subjects were classified as having abnormal balance with the Mini-Balance Evaluations Systems Test (71% abnormal) than with the Sensory Organization Test (24% abnormal) in our cohort of people with Parkinson's disease. There were no subjects with a normal Mini-Balance Evaluations Systems Test score but abnormal Sensory Organization Test score. In contrast, there were 21 subjects who had an abnormal Mini-Balance Evaluations Systems Test score but normal Sensory Organization Test scores. Findings from this study suggest that investigation of sensory integration deficits, alone, may not be able to identify all types of balance deficits found in patients with Parkinson's disease. Thus, a comprehensive approach should be used to test of multiple balance systems to provide

Preferences and concerns for care needs in advanced Parkinson's disease: a qualitative study of couples.

PubMed

Habermann, Barbara; Shin, Ju Young

2017-06-01

To explore how couples with Parkinson's disease discuss their needs, concerns and preferences at the advanced stages of illness. The majority of care for people with Parkinson's disease is provided at home by family members. Parkinson's disease is characterised by a slow progressive decline with care needs often exceeding a decade. A descriptive qualitative study with 14 couples. Data were collected on two occasions over a one-month period using semi-structured interviews, with both individual and couple interviews. Data were analysed thematically by the research team. All participants discussed the strong desire to remain in their homes for as long as possible. For the people with Parkinson's disease, placement to long-term facilities was not an option to be considered. For spouses, there was an acknowledgement there may come a time when they could no longer continue to provide care. Concerns regarding falls, choking, voice production, financial strain and need for prognostic information from providers were influences on what they believed the future would hold and the decisions they would need to make. The need for improved communication between providers and Parkinson's disease couples is evident. Interventions to support the couple in their discussions and decision-making regarding remaining in the home or not, and options to support advanced care needs are required. Nurses can help support decision-making by providing tangible information regarding the advanced stages of Parkinson's disease including adequate prognostic information. © 2016 John Wiley & Sons Ltd.

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

A molecular analysis of the GBA gene in Caucasian South Africans with Parkinson's disease.

PubMed

Barkhuizen, Melinda; Anderson, David G; van der Westhuizen, Francois H; Grobler, Anne F

2017-03-01

The molecular basis of Parkinson's disease in South African population groups remains elusive. To date, substitutions in the GBA gene are the most common large-effect genetic risk factor for Parkinson's disease. The primary objective of this study was to determine the prevalence of GBA substitutions in South Africans with idiopathic Parkinson's disease. Participants were recruited from tertiary hospitals in the Gauteng Province in South Africa. All participants were screened for substitutions in GBA exon 8-11 and the full coding region was analysed in 20 participants. Peripheral β -glucocerebrosidase enzymatic activity of GBA -carriers was measured in mixed leukocytes. Of 105 Caucasian Parkinson's disease participants (82.7% Afrikaner) with an average age of disease onset of 61.9 ± 12.2 years and 40 controls (age 73.4 ± 12.4 years) were included. Heterozygous GBA substitutions were identified in 12.38% of affected participants (p.G35A, p.E326K, p.I368T, p.T369M, p.N370S, p.P387L and p.K441N) and 5.00% of controls (p.E326K and p.T369M). The substitutions ranged from predicted benign to moderately damaging; with p.E326K and p.T369M most prevalent, followed by the Afrikaner Gaucher disease substitution p.P387L. Severe Gaucher disease mutations, like p.L444P, were absent in this cohort. Enzyme activity analysis revealed a nonsignificant reduction in the GBA -Parkinson's disease individuals (14.49 ± 2.30 nmol/h/mg protein vs. 15.98 ± 3.06 nmol/h/mg in control samples). GBA substitutions occur in both young-onset and late-onset Parkinson's cases in the cohort. Mild GBA substitutions that may not cause Gaucher disease were a common risk factor for Parkinson's disease in the participant group.

A Multicenter Comparative Study of Impulse Control Disorder in Latin American Patients With Parkinson Disease.

PubMed

Ramírez Gómez, Carolina Candelaria; Serrano Dueñas, Marcos; Bernal, Oscar; Araoz, Natalia; Sáenz Farret, Michel; Aldinio, Victoria; Montilla, Verónica; Micheli, Federico

Impulse control disorder (ICD) is a common adverse effect in patients with Parkinson disease who receive dopamine agonists; however, other factors are involved in its manifestations. To study the frequency and factors involved in the development of this adverse effect in a Latin American population, we conducted a cross-sectional multicenter study. Two hundred fifty-five patients in 3 Latin American centers were evaluated by examination and application of scales (Unified Parkinson's Disease Rating Scale, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale, Hoehn and Yahr, Clinical Impression of Severity Index for Parkinson's Disease). Of the patients, 27.4% had ICD, most of whom were on dopamine agonists. Other associated risk factors included a younger age at onset of Parkinson disease, moderate symptoms, a shorter evolution of the clinical manifestations, rapid eye movement (REM) sleep disorder behavior, and the consumption of tea, mate, and alcohol. The frequency of ICD is higher in Latin America than in Anglo-Saxon populations. Consuming tea and mate, in addition to the use of dopamine agonists, is a factor that may demonstrate a genetic link that predisposes patients to the establishment of an ICD.

Involvement of Gaucher Disease Mutations in Parkinson Disease.

PubMed

Vilageliu, Lluisa; Grinberg, Daniel

2017-01-01

Gaucher disease is an autosomal recessive lysosomal storage disorder, caused by mutations in the GBA gene. The frequency of Gaucher disease patients and heterozygote carriers that developed Parkinson disease has been found to be above that of the control population. This fact suggests that mutations in the GBA gene can be involved in Parkison's etiology. Analysis of large cohorts of patients with Parkinson disease has shown that there are significantly more cases bearing GBA mutations than those found among healthy individuals. Functional studies have proven an interaction between α-synuclein and GBA, the levels of which presented an inverse correlation. Mutant GBA proteins cause increases in α-synuclein levels, while an inhibition of GBA by α-synuclein has been also demonstrated. Saposin C, a coactivator of GBA, has been shown to protect GBA from this inhibition. Among the GBA variants associated with Parkinson disease, E326K seems to be one of the most prevalent. Interestingly, it is involved in Gaucher disease only when it forms part of a double-mutant allele, usually with the L444P mutation. Structural analyses have revealed that both residues (E326 and L444) interact with Saposin C and, probably, also with α-synuclein. This could explain the antagonistic role of these two proteins in relation to GBA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Chronic pain and pain processing in Parkinson's disease.

PubMed

Blanchet, Pierre J; Brefel-Courbon, Christine

2017-10-12

Pain is experienced by the vast majority of patients living with Parkinson's disease. It is most often of nociceptive origin, but may also be ascribed to neuropathic (radicular or central) or miscellaneous sources. The recently validated King's Parkinson's Disease Pain Scale is based on 7 domains including musculoskeletal pain, chronic body pain (central or visceral), fluctuation-related pain, nocturnal pain, oro-facial pain, pain with discolouration/oedema/swelling, and radicular pain. The basal ganglia integrate incoming nociceptive information and contribute to coordinated motor responses in pain avoidance and nocifensive behaviors. In Parkinson's disease, nigral and extra-nigral pathology, involving cortical areas, brainstem nuclei, and spinal cord, may contribute to abnormal central nociceptive processing in patients experiencing pain or not. The dopamine deficit lowers multimodal pain thresholds that are amenable to correction following levodopa dosing. Functional brain imaging with positron emission tomography following administration of H 2 15 O revealed abnormalities in the sensory discriminative processing of pain (insula/SII), as well as in the affective motivational processing of pain (anterior cingulate cortex, prefrontal cortex). Pain management is dependent on efforts invested in diagnostic accuracy to distinguish nociceptive from neuropathic pain. Treatment requires an integrated approach including strategies to lessen levodopa-related response fluctuations, in addition to other pharmacological and non-pharmacological options such as deep brain stimulation and rehabilitation. Copyright © 2017. Published by Elsevier Inc.

White matter lesions in Parkinson disease

PubMed Central

Bohnen, Nicolaas I.; Albin, Roger L.

2013-01-01

Pure vascular parkinsonism without evidence of nigral Lewy body pathology may occur as a distinct clinicopathological entity, but a much more frequent occurrence is the comorbid presence of age-associated white matter lesions (WMLs) in idiopathic Parkinson disease (PD). WMLs are associated with motor and cognitive symptoms in otherwise normal elderly individuals. Comorbid WMLs are, therefore, expected to contribute to clinical symptoms in PD. Studies of WMLs in PD differ with regard to methods of assessment of WML burden and the patient populations selected for analysis, but converging evidence suggests that postural stability and gait motor functions are predominantly affected. WMLs are described to contribute to dementia in Alzheimer disease, and emerging but inconclusive evidence indicates similar effects in PD. In this article, we review the literature addressing the occurrence and impact of WMLs in PD, and suggest that WMLs may exacerbate or contribute to some motor and cognitive deficits associated with PD. We review existing and emerging methods for studying white matter pathology in vivo, and propose future research directions. PMID:21343896

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

Monamine oxidase inhibitors: current and emerging agents for Parkinson disease.

PubMed

Fernandez, Hubert H; Chen, Jack J

2007-01-01

Monoamine oxidase type B (MAO-B) is the predominant isoform responsible for the metabolic breakdown of dopamine in the brain. Selective inhibition of brain MAO-B results in elevation of synaptosomal dopamine concentrations. Data have been reported regarding the selective MAO-B inhibitors, rasagiline and selegiline, for the symptomatic treatment of Parkinson disease (PD). Selegiline has demonstrated efficacy as monotherapy in patients with early PD (Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism study), but evidence of selegiline efficacy as adjunctive treatment in levodopa-treated PD patients with motor fluctuations is equivocal. A new formulation of selegiline (Zydis selegiline) has been evaluated in 2 small, placebo-controlled studies as adjunctive therapy to levodopa. The Zydis formulation allows pregastric absorption of selegiline, minimizing first-pass metabolism, and thereby increasing selegiline bioavailability and reducing the concentration of amphetamine metabolites. Rasagiline is a selective, second-generation, irreversible MAO-B inhibitor, with at least 5 times the potency of selegiline in vitro and in animal models. Rasagiline has demonstrated efficacy in 1 large, randomized, double-blind, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson's Disease Outpatients) as initial monotherapy in patients with early PD, and in 2 large, controlled trials (Parkinson's Rasagiline: Efficacy and Safety in the Treatment of "Off," Lasting Effect in Adjunct Therapy With Rasagiline Given Once Daily) as adjunctive treatment in levodopa-treated PD patients with motor fluctuations. Unlike selegiline, rasagiline is an aminoindan derivative with no amphetamine metabolites. A randomized clinical trial is underway to confirm preclinical and preliminary clinical data suggesting rasagiline has disease-modifying effects.

Downward finger displacement distinguishes Parkinson disease dementia from Alzheimer disease.