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Symptoms in Parkinson's disease

Sanna Rauhamäki, Pekka A Postila, Sanna Niinivehmas, Sami Kortet, Emmi Schildt, Mira Pasanen, Elangovan Manivannan, Mira Ahinko, Pasi Koskimies, Niina Nyberg, Pasi Huuskonen, Elina Multamäki, Markku Pasanen, Risto O Juvonen, Hannu Raunio, Juhani Huuskonen, Olli T Pentikäinen
Monoamine oxidase B (MAO-B) catalyzes deamination of monoamines such as neurotransmitters dopamine and norepinephrine. Accordingly, small-molecule MAO-B inhibitors potentially alleviate the symptoms of dopamine-linked neuropathologies such as depression or Parkinson's disease. Coumarin with a functionalized 3-phenyl ring system is a promising scaffold for building potent MAO-B inhibitors. Here, a vast set of 3-phenylcoumarin derivatives was designed using virtual combinatorial chemistry or rationally de novo and synthesized using microwave chemistry...
2018: Frontiers in Chemistry
Yong Wang, Ge-Juan Zhang, Yi-Na Sun, Lu Yao, Hui-Sheng Wang, Cheng-Xue Du, Li Zhang, Jian Liu
L-DOPA-induced dyskinesia (LID) is a frequent complication of chronic L-DOPA therapy in the clinical treatment of Parkinson's disease (PD). The pathogenesis of LID involves complex molecular mechanisms in the striatum. Metabolomics can shed light on striatal metabolic alterations in LID. In the present study, we compared metabolomics profiles of striatum tissue from Parkinsonian rats with or without dyskinetic symptoms after chronic L-DOPA administration. A liquid chromatography-mass spectrometry based global metabolomics method combined with multivariate statistical analyses were used to detect candidate metabolites associated with LID...
March 15, 2018: Behavioural Brain Research
Omid Abbasi, Jan Hirschmann, Lena Storzer, Tolga Esat Özkurt, Saskia Elben, Jan Vesper, Lars Wojtecki, Georg Schmitz, Alfons Schnitzler, Markus Butz
Deep brain stimulation (DBS) is an established therapy to treat motor symptoms in movement disorders such as Parkinson's disease (PD). The mechanisms leading to the high therapeutic effectiveness of DBS are poorly understood so far, but modulation of oscillatory activity is likely to play an important role. Thus, investigating the effect of DBS on cortical oscillatory activity can help clarifying the neurophysiological mechanisms of DBS. Here, we aimed at scrutinizing changes of cortical oscillatory activity by DBS at different frequencies using magnetoencephalography (MEG)...
March 15, 2018: NeuroImage
Ernest Dallé, Musa V Mabandla
This review aims to shed light on the relationship that involves exposure to early life stress, depression and Parkinson's disease (PD). A systematic literature search was conducted in Pubmed, MEDLINE, EBSCOHost and Google Scholar and relevant data were submitted to a meta-analysis . Early life stress may contribute to the development of depression and patients with depression are at risk of developing PD later in life. Depression is a common non-motor symptom preceding motor symptoms in PD. Stimulation of regions contiguous to the substantia nigra as well as dopamine (DA) agonists have been shown to be able to attenuate depression...
March 19, 2018: Molecular Brain
Susanna Nuvoli, Barbara Palumbo, Simona Malaspina, Giuseppe Madeddu, Angela Spanu
Nuclear medicine procedures are widely used as "in vivo" biomarkers in a large number of brain diseases, especially in the diagnosis of Parkinson's disease (PD) and of parkinsonian disorders (pD). Furthermore, nuclear medicine is used in the differential diagnosis of dementias especially Alzheimer's disease (AD) and dementia with Lewy's bodies (LBD) which share many clinical symptoms and often LBD is misdiagnosed as AD. The differential diagnosis between these clinical entities is crucial for treatment since LBD also shares some clinical symptoms with parkinsonian disorders...
March 20, 2018: Hellenic Journal of Nuclear Medicine
Moran Gilat, Ana Lígia Silva de Lima, Bastiaan R Bloem, James M Shine, Jorik Nonnekes, Simon J G Lewis
Freezing of gait is a devastating symptom of Parkinson's disease and other forms of parkinsonism. It poses a major burden on both patients and their families, as freezing often leads to falls, fall-related injuries and a loss of independence. Treating freezing of gait is difficult for a variety of reasons: it has a paroxysmal and unpredictable nature; a multifaceted pathophysiology, with an interplay between motor elements (disturbed stepping mechanisms) and non-motor elements (cognitive decline, anxiety); and a complex (and likely heterogeneous) underlying neural substrate, involving multiple failing neural networks...
March 12, 2018: Parkinsonism & related Disorders
Benjamin D Wissel, Alok K Dwivedi, Aristide Merola, Danielle Chin, Cara Jacob, Andrew P Duker, Jennifer E Vaughan, Lilia Lovera, Kathrin LaFaver, Ariel Levy, Anthony E Lang, Francesca Morgante, Melissa Jill Nirenberg, Christopher Stephen, Nutan Sharma, Alberto Romagnolo, Leonardo Lopiano, Bettina Balint, Xin X Yu, Kailash P Bhatia, Alberto J Espay
OBJECTIVE: To ascertain demographic and clinical features of Parkinson disease (PD) associated with functional neurological features. METHODS: A standardised form was used to extract data from electronic records of 53 PD patients with associated functional neurological disorders (PD-FND) across eight movement disorders centres in the USA, Canada and Europe. These subjects were matched for age, gender and disease duration to PD patients without functional features (PD-only)...
March 16, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
Rubens Gisbert Cury, Margarete de Jesus Carvalho, Fernando Jeyson Lopez Lasteros, Alice Estevo Dias, Maria Gabriela Dos Santos Ghilardi, Anderson Rodrigues Brandão Paiva, Artur Martins Coutinho, Carlos Alberto Buchpiguel, Manoel J Teixeira, Egberto Reis Barbosa, Erich Talamoni Fonoff
BACKGROUND: Olfactory dysfunction is a non-motor symptom of Parkinson's disease (PD) associated with reduction in quality of life. There is no evidence on whether improvements in olfaction after subthalamic deep brain stimulation (STN-DBS) may be directly attributable to motor improvement or whether this reflect a direct effect of DBS on olfactory brain areas. The aim of this study was to evaluate the effect of DBS on olfactory function (OF) in PD as well as to explore the correlation between these changes and changes in motor symptoms and brain metabolism...
March 13, 2018: World Neurosurgery
Manon Auffret, Sophie Drapier, Marc Vérin
Apomorphine is now recognized as the oldest antiparkinsonian drug on the market. Though still underused, it is increasingly prescribed in Europe for patients with advanced Parkinson's disease (PD) with motor fluctuations. However, its history is far from being limited to movement disorders. This paper traces the history of apomorphine, from its earliest empirical use, to its synthesis, pharmacological development, and numerous indications in human and veterinary medicine, in light of its most recent uses and newest challenges...
March 15, 2018: Drugs in R&D
Altair B Dos Santos, Kristi A Kohlmeier, Marcelo E Rocha, George E Barreto, Jeferson A Barreto, Ana Carla A de Souza, Marcos A Bezerra
Imbalances in metals have emerged as playing a role in the pathophysiology of Parkinson's Disease (PD). Monitoring of metal levels could serve as a biomarker of presence, or future development, of this disease. To this end, we evaluated the ability of flame atomic absorption spectrometry (FAAS) to assess the concentrations of Ca, Fe and Zn in hair of PD patients and to investigate if there was an association with age and disease duration. Hair samples were collected from 26 clinically-diagnosed PD patients, and 33 healthy individuals...
May 2018: Journal of Trace Elements in Medicine and Biology
Jing Gan, Ying Wan, Junjie Shi, Mingzhu Zhou, Zhiyin Lou, Zhenguo Liu
BACKGROUND: Constipation is one of the most frequent non-motor symptoms (NMS) in Parkinson's disease (PD) and the prevalence of constipation in PD patients varies among different studies. We designed this study to survey the prevalence and clinical characteristics of subjective constipation and the appearance chronology between the emergence of constipation and onset of motor symptoms in PD patients from Shanghai, China. METHODS: 268 PD patients were continuously recruited into this study...
March 15, 2018: BMC Neurology
Farzaneh Ghazi Sherbaf, Mahtab Mojtahed Zadeh, Maryam Haghshomar, Mohammad Hadi Aarabi
Psychiatric symptoms and motor impairment are major contributions to the poor quality of life in patients with Parkinson's disease (PD). Here, we applied a novel diffusion-weighted imaging approach, diffusion MRI connectometry, to investigate the correlation of quality of life, evaluated by Parkinson's Disease Questionnaire (PDQ39) with the white matter structural connectivity in 27 non-demented PD patients (disease duration of 5.3 ± 2.9 years, H and Y stage = 1.5 ± 0.6, UPDRS-III = 13.7 ± 6.5, indicating unilateral and mild motor involvement)...
March 14, 2018: Acta Neurologica Belgica
Carlo Cattaneo, Jaime Kulisevsky, Viviana Tubazio, Paola Castellani
INTRODUCTION: Chronic pain is an important yet overlooked non-motor symptom of Parkinson's disease (PD), caused by an imbalance of the dopaminergic and glutamatergic systems. Safinamide has a multimodal mechanism of action, dopaminergic (reversible MAO-B inhibition) and non-dopaminergic (modulation of the abnormal glutamate release), that might be beneficial for both motor and non-motor symptoms. OBJECTIVES: To investigate the long-term (2-year) efficacy of safinamide on PD chronic pain and to confirm the positive effects observed after 6 months of treatment...
March 14, 2018: Advances in Therapy
Adam J Stark, Christopher T Smith, Kalen J Petersen, Paula Trujillo, Nelleke C van Wouwe, Manus J Donahue, Robert M Kessler, Ariel Y Deutch, David H Zald, Daniel O Claassen
Parkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D2/3 receptors can improve motor and non-motor symptoms. However, data regarding the combined pattern of D2/3 receptor binding in both striatal and extrastriatal regions in PD are limited...
2018: NeuroImage: Clinical
Ruwei Ou, Qianqian Wei, Bei Cao, Wei Song, Yanbing Hou, Hui Liu, Xiaoqin Yuan, Bi Zhao, Ying Wu, Huifang Shang
Objective: To explore the clinical predictors of freezing of gait (FOG) in Chinese patients with Parkinson's disease (PD). Methods: This study included 225 patients with PD who completed a three-year follow-up visit. The end-point was the presence of FOG (freezers), which was assessed during the follow-up visit. Group comparisons were conducted, followed by a further forward binary logistic regression analysis. Results: Eighty-five patients with PD (38%) had developed FOG at the end of study...
March 2018: Brain and Behavior
Sara Ekmark-Lewén, Veronica Lindström, Astrid Gumucio, Elisabeth Ihse, Anish Behere, Philipp J Kahle, Eva Nordström, Maria Eriksson, Anna Erlandsson, Joakim Bergström, Martin Ingelsson
Introduction: Intraneuronal inclusions of alpha-synuclein are commonly found in the brain of patients with Parkinson's disease and other α-synucleinopathies. The correlation between alpha-synuclein pathology and symptoms has been studied in various animal models. In (Thy-1)-h[A30P] alpha-synuclein transgenic mice, behavioral and motor abnormalities were reported from 12 and 15 months, respectively. The aim of this study was to investigate whether these mice also display symptoms at earlier time points...
March 2018: Brain and Behavior
Aleksander H Erga, Ingvild Dalen, Anastasia Ushakova, Janete Chung, Charalampos Tzoulis, Ole Bjørn Tysnes, Guido Alves, Kenn Freddy Pedersen, Jodi Maple-Grødem
Introduction: Impulse control disorders (ICDs) are frequent non-motor symptoms in Parkinson's disease (PD), with potential negative effects on the quality of life and social functioning. ICDs are closely associated with dopaminergic therapy, and genetic polymorphisms in several neurotransmitter pathways may increase the risk of addictive behaviors in PD. However, clinical differentiation between patients at risk and patients without risk of ICDs is still troublesome. The aim of this study was to investigate if genetic polymorphisms across several neurotransmitter pathways were associated with ICD status in patients with PD...
2018: Frontiers in Neurology
Anand Rughani, Jason M Schwalb, Christos Sidiropoulos, Julie Pilitsis, Adolfo Ramirez-Zamora, Jennifer A Sweet, Sandeep Mittal, Alberto J Espay, Jorge Gonzalez Martinez, Aviva Abosch, Emad Eskandar, Robert Gross, Ron Alterman, Clement Hamani
QUESTION 1: Is bilateral subthalamic nucleus deep brain stimulation (STN DBS) more, less, or as effective as bilateral globus pallidus internus deep brain stimulation (GPi DBS) in treating motor symptoms of Parkinson's disease, as measured by improvements in Unified Parkinson's Disease Rating Scale, part III (UPDRS-III) scores? RECOMMENDATION: Given that bilateral STN DBS is at least as effective as bilateral GPi DBS in treating motor symptoms of Parkinson's disease (as measured by improvements in UPDRS-III scores), consideration can be given to the selection of either target in patients undergoing surgery to treat motor symptoms...
March 12, 2018: Neurosurgery
Hiroshige Fujishiro, Masato Okuda, Kunihiro Iwamoto, Seiko Miyata, Youta Torii, Shuji Iritani, Norio Ozaki
AIMS: REM sleep behavior disorder (RBD) and psychiatric symptoms often antedate the clinical diagnosis of Parkinson's disease / dementia with Lewy bodies. The purpose of this study is to investigate RBD and its relevance to Lewy body disease (LBD) in patients with late-onset psychiatric disorders. METHODS: Study subjects included 19 patients with late-onset psychiatric disorders who exhibited REM sleep without atonia (RWA), which is a hallmark of RBD on polysomnography, at our psychiatric ward...
March 14, 2018: Psychiatry and Clinical Neurosciences
Ivan Martinez-Valbuena, Irene Amat-Villegas, Rafael Valenti-Azcarate, Maria Del Mar Carmona-Abellan, Irene Marcilla, Maria-Teresa Tuñon, Maria-Rosario Luquin
Parkinson's disease patients experience a wide range of non-motor symptoms that may be provoked by deposits of phosphorylated α-synuclein in the peripheral nervous system. Pre-existing diabetes mellitus might be a risk factor for developing Parkinson's disease, and indeed, nearly 60% of Parkinson's disease patients are insulin resistant. Thus, we have investigated whether phosphorylated α-synuclein is deposited in pancreatic tissue of subjects with synucleinopathies. We studied pancreatic tissue from 39 subjects diagnosed with Parkinson's disease, Lewy body Dementia or incidental Lewy bodies disease, as well as that from 34 subjects with diabetes mellitus and a normal neuropathological examination, and 52 subjects with a normal neuropathological examination...
March 13, 2018: Acta Neuropathologica
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