Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Parkinson Disease: HELP
Articles from UCLA
Based on 208 articles published since 2010

These are the 208 published articles about Parkinson Disease that originated from UCLA during 2010-2020.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9
1 Editorial Pesticides and Parkinson's disease: is it in your genes? 2014

Barnhill, Lisa M / Bronstein, Jeff M. ·Department of Neurology & Molecular Toxicology Program, David Geffen School of Medicine, Los Angeles, CA 90095, USA. ·Neurodegener Dis Manag · Pubmed #25095814.

ABSTRACT: -- No abstract --

2 Review The Search for Environmental Causes of Parkinson's Disease: Moving Forward. 2018

Chen, Honglei / Ritz, Beate. ·Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing, MI, USA. · Department of Epidemiology and Environmental Health Sciences, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA. ·J Parkinsons Dis · Pubmed #30584168.

ABSTRACT: It is widely believed that environmental exposures contribute to the vast majority of late-onset sporadic Parkinson's disease (PD), alone or via interactions with genetic factors. The search for environmental causes of PD has however been hampered by lack of understanding the prodromal phase of PD development and the difficulties in exposure assessment during this prolonged period. On the other hand, the existence of this prodromal period, along with an increasingly better understanding of PD prodromal symptoms, provides an exciting opportunity to identify environmental factors that initiate PD pathogenesis and/or modify its progression. For prevention efforts, this prodromal stage is of a major interest. Targeting factors that enter the body via the nose or gut has become even more important since the discovery of α-synuclein aggregates in the enteric and olfactory nervous systems. In this paper, we speculate about novel research hypotheses and approaches that may help us better define the role of environment in PD etiology, especially during its extended and complex prodromal phase.

3 Review NMDA antagonists for treating the non-motor symptoms in Parkinson's disease. 2018

Vanle, Brigitte / Olcott, William / Jimenez, Jaime / Bashmi, Luma / Danovitch, Itai / IsHak, Waguih William. ·Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA. brigitte.vanle@yahoo.com. · Medical College of Wisconsin, Wausau, WI, USA. brigitte.vanle@yahoo.com. · Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA. · David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. ·Transl Psychiatry · Pubmed #29907742.

ABSTRACT: Among patients with Parkinson's disease (PD), depression is prevalent and disabling, impacting both health outcomes and quality of life. There is a critical need for alternative pharmacological methods to treat PD depression, as mainstream antidepressant drugs are largely ineffective in this population. Currently, there are no recommendations for the optimal treatment of PD neuropsychiatric symptoms. Given the dual antidepressant and anti-dyskinetic effects of ketamine and other N-methyl-D-aspartate (NMDA) antagonists for PD, this review aims to examine the current evidence of NMDA antagonists for treating neuropsychiatric symptoms, including memantine, amantadine, ketamine, dizoclopine, and d-cycloserine. A comprehensive literature search was conducted using the PubMed database. We also searched the following databases up to March 1, 2018: Ovid MEDLINE, PsycINFO, CINAHL, Google Scholar, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. The following keywords were used: NMDA antagonist and Parkinson's disease. Two authors independently reviewed the articles identified from the search using specific selection criteria, focusing on studies of mood, psychiatric condition, depression, cognition, and quality of life, and the consensus was reached on the 20 studies included. There is a preliminary evidence that NMDA antagonists may modulate psychiatric symptoms in PD. However, current evidence of psychiatric symptom-modifying effects is inconclusive and requires that further trials be conducted in PD. The repurposing of old NMDA antagonists, such as ketamine for depression and newer therapies, such as rapastinel, suggests that there is an emerging place for modulating the glutamatergic system for treating non-motor symptoms in PD.

4 Review Paradoxical Decision-Making: A Framework for Understanding Cognition in Parkinson's Disease. 2018

Perugini, Alessandra / Ditterich, Jochen / Shaikh, Aasef G / Knowlton, Barbara J / Basso, Michele A. ·Fuster Laboratory of Cognitive Neuroscience, Department of Psychiatry and Biobehavioral Sciences, Department of Neurobiology, Semel Institute for Neuroscience and Human Behavior, Brain Research Institute, The David Geffen School of Medicine, Los Angeles, CA 90095, USA. · Center for Neuroscience and Department of Neurobiology, Physiology, and Behavior, University of California, Davis, CA, USA. · Department of Neurology, Case Western Reserve University, Cleveland, OH 44106, USA. · Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA. · Fuster Laboratory of Cognitive Neuroscience, Department of Psychiatry and Biobehavioral Sciences, Department of Neurobiology, Semel Institute for Neuroscience and Human Behavior, Brain Research Institute, The David Geffen School of Medicine, Los Angeles, CA 90095, USA. Electronic address: mbasso@mednet.ucla.edu. ·Trends Neurosci · Pubmed #29747856.

ABSTRACT: People with Parkinson's disease (PD) show impaired decision-making when sensory and memory information must be combined. This recently identified impairment results from an inability to accumulate the proper amount of information needed to make a decision and appears to be independent of dopamine tone and reinforcement learning mechanisms. Although considerable work focuses on PD and decisions involving risk and reward, in this Opinion article we propose that the emerging findings in perceptual decision-making highlight the multisystem nature of PD, and that unraveling the neuronal circuits underlying perceptual decision-making impairment may help in understanding other cognitive impairments in people with PD. We also discuss how a decision-making framework may be extended to gain insights into mechanisms of motor impairments in PD.

5 Review Asymmetric neuromodulation of motor circuits in Parkinson's disease: The role of subthalamic deep brain stimulation. 2017

Lizarraga, Karlo J / Luca, Corneliu C / De Salles, Antonio / Gorgulho, Alessandra / Lang, Anthony E / Fasano, Alfonso. ·Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital and Division of Neurology, University of Toronto, Toronto, Ontario, Canada. · Department of Neurology, Jackson Memorial Hospital and University of Miami Miller School of Medicine, Miami, Florida, USA. · Department of Neurosurgery, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA. · Krembil Research Institute, Toronto, Ontario, Canada. ·Surg Neurol Int · Pubmed #29184712.

ABSTRACT: Whereas hemispheric dominance is well-established for appendicular motor control in humans, the evidence for dominance in axial motor control is still scarce. In Parkinson's disease (PD), unilateral (UL) onset of appendicular motor symptoms corresponds with asymmetric neurodegeneration predominantly affecting contralateral nigrostriatal circuits. Disease progression yields bilateral and axial motor symptoms but the initial appendicular asymmetry usually persists. Furthermore, there is evidence for hemispheric dominance for axial motor dysfunction in some of these patients. Dopaminergic medications improve appendicular symptoms but can also produce motor complications over time. Once these complications develop, bilateral (BL) deep brain stimulation (DBS) of the subthalamic nuclei (STN) can significantly improve appendicular symptoms while reducing medication doses and motor complications. Conversely, axial motor symptoms remain a significant source of disability, morbidity, and mortality for patients with PD. These axial symptoms do not necessarily improve with dopaminergic therapy, might not respond, and could even worsen after BL-DBS. In contrast to medications, DBS provides the opportunity to modify stimulation parameters for each cerebral hemisphere. Identical, BL-DBS of motor circuits with hemispheric dominance in PD might produce overstimulation on one side and/or understimulation on the other side, which could contribute to motor dysfunction. Several studies based on asymmetry of appendicular motor symptoms already support an initial UL rather than BL approach to DBS in some patients. The response of axial motor symptoms to UL versus BL-DBS remains unclear. Nonetheless, UL-DBS, staged BL-DBS, or asymmetric programming of BL-DBS could also be considered in patients with PD.

6 Review Complementary and Alternative Medicine and Exercise in Nonmotor Symptoms of Parkinson's Disease. 2017

Subramanian, Indu. ·UCLA/West LA VA, Los Angeles, CA, United States. Electronic address: ISubramanian@mednet.ucla.edu. ·Int Rev Neurobiol · Pubmed #28805568.

ABSTRACT: The use of complementary and alternative medicine (CAM) therapy in nonmotor symptoms (NMS) for Parkinson disease (PD) is growing worldwide. Well-performed, systematic evidence-based research is largely lacking in this area and many studies include various forms of CAM with small patient numbers and a lack of standardization of the approaches studied. Taichi, Qigong, dance, yoga, mindfulness, acupuncture, and other CAM therapies are reviewed and there is some evidence for the following: Taichi in sleep and PDQ39; dance in cognition, apathy, and a mild trend to improved fatigue; yoga in PDQ39; and acupuncture in depression, PDQ39, and sleep. Exercise including occupational therapy (OT) and physical therapy (PT) has been studied in motor symptoms of PD and balance but only with small studies with a mounting evidence base for use of exercise in NMS of PD including PDQ39, sleep, fatigue, depression, and some subsets of cognition. Studies of OT and PT largely show some benefit to depression, apathy, and anxiety. Sustainability of an improvement has not been shown given short duration of follow up. Finding optimal control groups and blind for these interventions is also an issue. This is a very important area of study since patients want to be self-empowered and they want guidance on which form of exercise is the best. Additionally, evidence for PT and OT in NMS would give added weight to get these interventions covered through medical insurance.

7 Review Retinal Ganglion Cells and Circadian Rhythms in Alzheimer's Disease, Parkinson's Disease, and Beyond. 2017

La Morgia, Chiara / Ross-Cisneros, Fred N / Sadun, Alfredo A / Carelli, Valerio. ·IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy. · Neurology Unit, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. · Doheny Eye Institute, Los Angeles, CA, USA. · Department of Ophthalmology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA. ·Front Neurol · Pubmed #28522986.

ABSTRACT: There is increasing awareness on the role played by circadian rhythm abnormalities in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). The characterization of the circadian dysfunction parallels the mounting evidence that the hallmarks of neurodegeneration also affect the retina and frequently lead to loss of retinal ganglion cells (RGCs) and to different degrees of optic neuropathy. In the RGC population, there is the subgroup of cells intrinsically photosensitive and expressing the photopigment melanopsin [melanopsin-containing retinal ganglion cells (mRGCs)], which are now well known to drive the entrainment of circadian rhythms to the light-dark cycles. Thus, the correlation between the pathological changes affecting the retina and mRGCs with the circadian imbalance in these neurodegenerative diseases is now clearly emerging, pointing to the possibility that these patients might be amenable to and benefit from light therapy. Currently, this connection is better established for AD and PD, but the same scenario may apply to other neurodegenerative disorders, such as Huntington's disease. This review highlights similarities and differences in the retinal/circadian rhythm axis in these neurodegenerative diseases posing a working frame for future studies.

8 Review A practical review of gastrointestinal manifestations in Parkinson's disease. 2017

Su, Andrew / Gandhy, Rita / Barlow, Carrolee / Triadafilopoulos, George. ·Medicine, Stanford University School of Medicine, Stanford, CA, United states; Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, United States. Electronic address: andrewmsu@gmail.com. · The Parkinson's Institute and Clinical Center, Sunnyvale, CA, United states. Electronic address: rgandhy@parkinsonsinstitute.org. · The Parkinson's Institute and Clinical Center, Sunnyvale, CA, United states. Electronic address: cbarlow@parkinsonsinstitute.org. · Medicine, Stanford University School of Medicine, Stanford, CA, United states; Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, United states. Electronic address: vagt@stanford.edu. ·Parkinsonism Relat Disord · Pubmed #28258927.

ABSTRACT: Parkinson's disease (PD) is a chronic neurodegenerative disease with prominent motor and non-motor symptoms. Gastrointestinal (GI) dysfunction is among the most common and bothersome of non-motor symptoms that physicians will encounter while caring for their patients. Patients are subject to a wide variety of GI symptoms involving organs from the oropharynx to the anorectum. Our awareness and understanding of GI involvement in PD continues to evolve. In this review, we use a gastroenterologist's perspective to provide practical considerations for the diagnosis and symptom-based management of GI dysfunction seen in PD. Our aim is to assist neurologists and specialists as they encounter these symptoms while caring for the many neurologic manifestations of PD.

9 Review Speech and language adverse effects after thalamotomy and deep brain stimulation in patients with movement disorders: A meta-analysis. 2017

Alomar, Soha / King, Nicolas K K / Tam, Joseph / Bari, Ausaf A / Hamani, Clement / Lozano, Andres M. ·King Abdulaziz University, Department of Surgery, Division of Neurosurgery, King Abdulaziz University Hospital, Jeddah, Saudi Arabia. · University of Toronto, Department of Surgery, Division of Neurosurgery, Toronto Western Hospital, Toronto, Ontario, Canada. · Department of Neurosurgery, National Neuroscience Institute, Singapore. · University of California Los Angeles, Department of Neurosurgery, Los Angeles, California, USA. ·Mov Disord · Pubmed #28124434.

ABSTRACT: BACKGROUND: The thalamus has been a surgical target for the treatment of various movement disorders. Commonly used therapeutic modalities include ablative and nonablative procedures. A major clinical side effect of thalamic surgery is the appearance of speech problems. OBJECTIVE: This review summarizes the data on the development of speech problems after thalamic surgery. METHODS: A systematic review and meta-analysis was performed using nine databases, including Medline, Web of Science, and Cochrane Library. We also checked for articles by searching citing and cited articles. We retrieved studies between 1960 and September 2014. RESULTS: Of a total of 2,320 patients, 19.8% (confidence interval: 14.8-25.9) had speech difficulty after thalamotomy. Speech difficulty occurred in 15% (confidence interval: 9.8-22.2) of those treated with a unilaterally and 40.6% (confidence interval: 29.5-52.8) of those treated bilaterally. Speech impairment was noticed 2- to 3-fold more commonly after left-sided procedures (40.7% vs. 15.2%). Of the 572 patients that underwent DBS, 19.4% (confidence interval: 13.1-27.8) experienced speech difficulty. Subgroup analysis revealed that this complication occurs in 10.2% (confidence interval: 7.4-13.9) of patients treated unilaterally and 34.6% (confidence interval: 21.6-50.4) treated bilaterally. After thalamotomy, the risk was higher in Parkinson's patients compared to patients with essential tremor: 19.8% versus 4.5% in the unilateral group and 42.5% versus 13.9% in the bilateral group. After DBS, this rate was higher in essential tremor patients. CONCLUSION: Both lesioning and stimulation thalamic surgery produce adverse effects on speech. Left-sided and bilateral procedures are approximately 3-fold more likely to cause speech difficulty. This effect was higher after thalamotomy compared to DBS. In the thalamotomy group, the risk was higher in Parkinson's patients, whereas in the DBS group it was higher in patients with essential tremor. Understanding the pathophysiology of speech disturbance after thalamic procedures is a priority. © 2017 International Parkinson and Movement Disorder Society.

10 Review Palliative care and Parkinson's disease: Meeting summary and recommendations for clinical research. 2017

Kluger, Benzi M / Fox, Siobhán / Timmons, Suzanne / Katz, Maya / Galifianakis, Nicholas B / Subramanian, Indu / Carter, Julie H / Johnson, Miriam J / Richfield, Edward W / Bekelman, David / Kutner, Jean S / Miyasaki, Janis. ·Department of Neurology, University of Colorado School of Medicine, Anschutz Medical Campus, 12631 E 17th Ave, Mail Stop B185, Aurora, CO 80045, USA. Electronic address: benzi.kluger@ucdenver.edu. · Centre for Gerontology and Rehabilitation, School of Medicine, University College Cork, The Bungalow, Block 13, St. Finbarr's Hospital, Douglas Road, Cork, Republic of Ireland. · Department of Neurology, University of California San Francisco, 4150 Clement St. #219G, San Francisco, CA 94143, USA. · Department of Neurology, University of California Los Angeles, 300 UCLA Medical Plaza, Suite B200, Los Angeles, CA 90095, USA. · Department of Neurology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, L226, Portland, OR 97239, USA. · Hull York Medical School, University of Hull, Hertford Building, Hull HU6 7RX, UK. · Department of Elderly Medicine, Leeds Teaching Hospitals Trust, UK. · Department of Internal Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, 12401 East 17th Avenue, Mail Stop B180, Aurora, CO 80045, USA; Department of Medicine, VA Eastern Colorado Health Care System, 1055 Clermont Street, Denver, CO 80220, USA. · Department of Internal Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, 12401 East 17th Avenue, Mail Stop B180, Aurora, CO 80045, USA. · Division of Neurology, University of Alberta, 13-103 Clinical Sciences Building, 11350-83 Avenue, Edmonton, Alberta T6G 2R3, Canada. ·Parkinsonism Relat Disord · Pubmed #28108265.

ABSTRACT: INTRODUCTION: Palliative care is an approach to caring for patients and families affected by serious illnesses that focuses on the relief of suffering through the management of medical symptoms, psychosocial issues, advance care planning and spiritual wellbeing. Over the past decade there has been an emerging clinical and research interest in the application of palliative care approaches to Parkinson's disease (PD) and outpatient palliative care services are now offered by several movement disorders centers. METHODS: An International Working Group Meeting on PD and Palliative Care supported by the Parkinson's Disease Foundation was held in October 2015 to review the current state of the evidence and to make recommendations for clinical research and practice. RESULTS: Topics included: 1) Defining palliative care for PD; 2) Lessons from palliative care for heart failure and other chronic illnesses; 3) Patient and caregiver Needs; 4) Needs assessment tools; 5) Intervention strategies; 6) Predicting prognosis and hospice referrals; 7) Choice of appropriate outcome measures; 8) Implementation, dissemination and education research; and 9) Need for research collaborations. We provide an overview of these discussions, summarize current evidence and practices, highlight gaps in our knowledge and make recommendations for future research. CONCLUSIONS: Palliative Care for PD is a rapidly growing area which holds great promise for improving outcomes for PD patients and their caregivers. While clinical research in this area can build from lessons learned in other diseases, there is a need for observational, methodological and interventional research to address the unique needs of PD patients and caregivers.

11 Review Parkinsonism. 2016

Keener, Adrienne M / Bordelon, Yvette M. ·Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California. ·Semin Neurol · Pubmed #27643900.

ABSTRACT: Parkinsonism is a clinical syndrome, which is characterized by bradykinesia, rigidity, rest tremor, and postural instability. Idiopathic Parkinson disease (PD) is the most common cause of this syndrome, though there are several other important etiologies that must be considered. These include the atypical Parkinsonian disorders multiple system atrophy (MSA), dementia with Lewy Bodies (DLB), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS); as well as secondary causes of parkinsonism. These various disease entities may be distinguished based on key clinical features, which is critical for the purposes of diagnosis, treatment, and prognosis.

12 Review Machine learning for large-scale wearable sensor data in Parkinson's disease: Concepts, promises, pitfalls, and futures. 2016

Kubota, Ken J / Chen, Jason A / Little, Max A. ·Department of Data Science, tranSMART Foundation, Wakefield, Massachusetts, USA. Ken.Kubota@transmartfoundation.org. · Verge Genomics, San Francisco, California, USA. · Interdepartmental Program in Bioinformatics, University of California at Los Angeles, Los Angeles, California, USA. · Aston University, Aston Triangle, Birmingham, United Kingdom. · Media Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. ·Mov Disord · Pubmed #27501026.

ABSTRACT: For the treatment and monitoring of Parkinson's disease (PD) to be scientific, a key requirement is that measurement of disease stages and severity is quantitative, reliable, and repeatable. The last 50 years in PD research have been dominated by qualitative, subjective ratings obtained by human interpretation of the presentation of disease signs and symptoms at clinical visits. More recently, "wearable," sensor-based, quantitative, objective, and easy-to-use systems for quantifying PD signs for large numbers of participants over extended durations have been developed. This technology has the potential to significantly improve both clinical diagnosis and management in PD and the conduct of clinical studies. However, the large-scale, high-dimensional character of the data captured by these wearable sensors requires sophisticated signal processing and machine-learning algorithms to transform it into scientifically and clinically meaningful information. Such algorithms that "learn" from data have shown remarkable success in making accurate predictions for complex problems in which human skill has been required to date, but they are challenging to evaluate and apply without a basic understanding of the underlying logic on which they are based. This article contains a nontechnical tutorial review of relevant machine-learning algorithms, also describing their limitations and how these can be overcome. It discusses implications of this technology and a practical road map for realizing the full potential of this technology in PD research and practice. © 2016 International Parkinson and Movement Disorder Society.

13 Review Of Pesticides and Men: a California Story of Genes and Environment in Parkinson's Disease. 2016

Ritz, Beate R / Paul, Kimberly C / Bronstein, Jeff M. ·Department of Epidemiology, Fielding School of Public Health, UCLA, 650 Charles Young Dr South, Los Angeles, CA, 90095-1772, USA. britz@ucla.edu. · Center for Occupational and Environmental Health, UCLA, Los Angeles, CA, USA. britz@ucla.edu. · Department of Neurology, Geffen School of Medicine, UCLA, 710 Westwood Plaza, Los Angeles, CA, 90095, USA. britz@ucla.edu. · Department of Epidemiology, Fielding School of Public Health, UCLA, 650 Charles Young Dr South, Los Angeles, CA, 90095-1772, USA. · Department of Neurology, Geffen School of Medicine, UCLA, 710 Westwood Plaza, Los Angeles, CA, 90095, USA. ·Curr Environ Health Rep · Pubmed #26857251.

ABSTRACT: At the start of the postgenomics era, most Parkinson's disease (PD) etiology cannot be explained by our knowledge of genetic or environmental factors alone. For more than a decade, we have explored gene-environment (GxE) interactions possibly responsible for the heterogeneity of genetic as well as environmental results across populations. We developed three pesticide exposure measures (ambient due to agricultural applications, home and garden use, and occupational use) in a large population-based case-control study of incident PD in central California. Specifically, we assessed interactions with genes responsible for pesticide metabolism (PON1); transport across the blood-brain barrier (ABCB1); pesticides interfering with or depending on dopamine transporter activity (DAT/SLC6A3) and dopamine metabolism (ALDH2); impacting mitochondrial function via oxidative/nitrosative stress (NOS1) or proteasome inhibition (SKP1); and contributing to immune dysregulation (HLA-DR). These studies established some specificity for pesticides' neurodegenerative actions, contributed biologic plausibility to epidemiologic findings, and identified genetically susceptible populations.

14 Review Long-Term Evaluation of Changes in Operative Technique and Hardware-Related Complications With Deep Brain Stimulation. 2015

Falowski, Steven M / Ooi, Yinn Cher / Bakay, Roy A E. ·St. Lukes University Health Network, Bethlehem, PA, USA. · Department of Neurosurgery, UCLA, Los Angeles, CA, USA. · Department of Neurosurgery, Rush University, Chicago, IL, USA. ·Neuromodulation · Pubmed #26245633.

ABSTRACT: BACKGROUND: Deep brain stimulation is the most frequent neurosurgical procedure for movement disorders. OBJECTIVE: While this elective procedure carries a low-risk profile, it is not free of complications. As a new procedure, the pattern of complications changed with experience and modification of surgical technique and equipment. METHODS: This review analyzes the most common hardware-related complications that may occur and techniques to avoid them. It is a retrospective review of 432 patients undergoing 1077 procedures over a 14-year period by one surgeon with emphasis on the analysis of surgical technique and the changes over time. Comparisons were made pre and postimplementation of different surgical techniques over different time periods. The epochs relate to the learning curve, new equipment, and new techniques. RESULTS: Overall lead revision was observed at 5.7%, extension revision at 3.2%, infection rate at 1.2%, infarct without intracerebral hemorrhage at 0.8%, and intracerebral hemorrhage at 2.5% with a permanent deficit of 0.2%. An analysis and change in surgical technique which involved isolating the lead from the skin surface at both the cranial and retro-auricular incision also demonstrated a substantial decrease in lead fracture rate and infection rate. There was no mortality. CONCLUSION: This large series of patients and long-term follow-up demonstrates that risks are very low in comparison with other neurosurgical procedures, but DBS is still an elective procedure that necessitates extensive care and precision. In a rapidly evolving field, attention to surgical technique is imperative and will keep rates of complications at a minimum.

15 Review Interactions of the histamine and hypocretin systems in CNS disorders. 2015

Shan, Ling / Dauvilliers, Yves / Siegel, Jerome M. ·Department of Psychiatry and Brain Research Institute, UCLA School of Medicine, Veterans' Affairs Greater Los Angeles Healthcare System (VA GLAHS), 16111 Plummer Street North Hills, 151A3, CA 91343, USA. · Centre de Référence Nationale Maladies Rares, Narcolepsie et Hypersomnie Idiopathique, Département de Neurologie, Hôpital Gui-de-Chauliac, INSERM U1061, 80 avenue Augustin Fliche, Montpellier 34295, France. ·Nat Rev Neurol · Pubmed #26100750.

ABSTRACT: Histamine and hypocretin neurons are localized to the hypothalamus, a brain area critical to autonomic function and sleep. Narcolepsy type 1, also known as narcolepsy with cataplexy, is a neurological disorder characterized by excessive daytime sleepiness, impaired night-time sleep, cataplexy, sleep paralysis and short latency to rapid eye movement (REM) sleep after sleep onset. In narcolepsy, 90% of hypocretin neurons are lost; in addition, two groups reported in 2014 that the number of histamine neurons is increased by 64% or more in human patients with narcolepsy, suggesting involvement of histamine in the aetiology of this disorder. Here, we review the role of the histamine and hypocretin systems in sleep-wake modulation. Furthermore, we summarize the neuropathological changes to these two systems in narcolepsy and discuss the possibility that narcolepsy-associated histamine abnormalities could mediate or result from the same processes that cause the hypocretin cell loss. We also review the changes in the hypocretin and histamine systems, and the associated sleep disruptions, in Parkinson disease, Alzheimer disease, Huntington disease and Tourette syndrome. Finally, we discuss novel therapeutic approaches for manipulation of the histamine system.

16 Review Effective delivery of apomorphine in the management of Parkinson disease: practical considerations for clinicians and Parkinson nurses. 2015

Bhidayasiri, Roongroj / Chaudhuri, K Ray / LeWitt, Peter / Martin, Anne / Boonpang, Kamolwan / van Laar, Teus. ·*Chulalongkorn Center of Excellence on Parkinson's Disease and Related Disorders, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; †Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA; ‡National Parkinson Foundation Centre of Excellence, King's College Hospital, Denmark Hill Campus, London, United Kingdom; §Wayne State University School of Medicine, Parkinson's Disease and Movement Disorders Program, Henry Ford West Bloomfield Hospital, West Bloomfield, MI; ║King's College Hospital, Denmark Hill Campus, London, United Kingdom; ¶Chulalongkorn Center of Excellence on Parkinson's Disease and Related Disorders, Bangkok, Thailand; and #Department of Neurology, Movement Disorder Center, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. ·Clin Neuropharmacol · Pubmed #25970277.

ABSTRACT: The clinical utility of long-term oral levodopa therapy in Parkinson disease (PD) is often limited by the emergence of motor complications. Over time, many patients with PD experience regular and/or unpredictable "off" periods, despite taking optimized oral medication regimens, with a major negative impact on their ability to undertake routine activities of daily living and consequently on their overall quality of life. One established approach for treating patients experiencing off periods and controlling motor fluctuations refractory to conventional oral drug therapy is the subcutaneous administration of the dopaminergic agonist apomorphine. This article outlines how the pharmacokinetic properties of apomorphine underpin its efficacy for the treatment of PD and provides practical guidance for the 3 main approaches in which it is used: subcutaneous intermittent apomorphine injection as a "rescue" therapy for off states, subcutaneous continuous apomorphine infusion for PD patients with intractable motor fluctuations as an alternative to other dopaminergic treatment, and in the apomorphine response (or challenge) test for assessment of dopamine-induced motor response in patients thought to have PD, or in establishing the optimal tolerated dose of apomorphine in patients already known to have PD. Also discussed is the management of potential adverse events with subcutaneous administration of apomorphine, the majority of which are mild and easily managed in practice. The importance of a multidisciplinary PD team in the optimal management of PD patients is now recognized, in particular the role of the specialist PD nurse.

17 Review The human histaminergic system in neuropsychiatric disorders. 2015

Shan, Ling / Bao, Ai-Min / Swaab, Dick F. ·Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, China; Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam 1105 BA, The Netherlands; Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles, CA 90095, USA; Neurobiology Research, Veterans Administration Greater Los Angeles Health Care System, 16111 Plummer Street, North Hills, CA 91343, USA. · Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address: baoaimin@zju.edu.cn. · Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam 1105 BA, The Netherlands. ·Trends Neurosci · Pubmed #25575625.

ABSTRACT: Histaminergic neurons are exclusively located in the hypothalamic tuberomamillary nucleus, from where they project to many brain areas. The histaminergic system is involved in basic physiological functions, such as the sleep-wake cycle, energy and endocrine homeostasis, sensory and motor functions, cognition, and attention, which are all severely affected in neuropsychiatric disorders. Here, we present recent postmortem findings on the alterations in this system in neuropsychiatric disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), depression, and narcolepsy. In addition, we highlight the need to validate animal models for these diseases and also for Tourette's syndrome (TS) in relation to alterations in the histaminergic system. Moreover, we discuss the potential for, and concerns over, the use of novel histamine 3 receptor (H3R) antagonists/inverse agonists as treatment for such disorders.

18 Review Transgenic rodent models to study alpha-synuclein pathogenesis, with a focus on cognitive deficits. 2015

Hatami, Asa / Chesselet, Marie-Francoise. ·Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, USA, ahatami@mednet.ucla.edu. ·Curr Top Behav Neurosci · Pubmed #25218491.

ABSTRACT: The aggregation of alpha-synuclein (aSyn) has been implicated in a number of degenerative diseases collectively termed synucleinopathies. Although most cases of synucleinopathies are idiopathic in nature, there are familial cases of these diseases that are due to mutations or multiplications of the gene coding for aSyn. Two of the most common synucleinopathies are Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Both of these diseases present with cognitive deficits, though with different clinical and temporal features. In PD, cognitive deficits are subtle, may occur before the onset of the classical motor symptoms, and only occasionally lead to dementia in the later stages of the disease. In contrast, dementia is the dominating feature of DLB from the disease onset. The impact of aSyn pathology on the development of neurobiological and behavioral impairments can be investigated using rodent models. There are currently several lines of transgenic mice overexpressing wild-type or mutated aSyn under various promoters. This review will provide an updated synopsis of the mouse lines available, summarize their cognitive deficits, and reflect on how deficits observed in these mice relate to the disease process in humans. In addition, we will review mouse lines where knockout strategies have been applied to study the effects of aSyn on various cognitive tasks and comment on how these lines have been used in combination with other transgenic strains, or with human aSyn overexpression by viral vectors. Finally, we will discuss the recent advent of bacterial artificial chromosome (BAC) transgenic models of PD and their effectiveness in modeling cognitive decline in PD.

19 Review Glia in the pathogenesis of neurodegenerative diseases. 2014

Verkhratsky, Alexei / Parpura, Vladimir / Pekna, Marcela / Pekny, Milos / Sofroniew, Michael. ·††Department of Neurobiology, University of California, Los Angeles, CA 90095, U.S.A. ·Biochem Soc Trans · Pubmed #25233406.

ABSTRACT: Exclusively neuron-centric approaches to neuropathological mechanisms have not resulted in major new breakthroughs in the prevention and therapy of neurodegenerative diseases. In the present paper, we review the role of glia in neurodegeneration in an attempt to identify novel targets that could be used to develop much-needed strategies for the containment and cure of neurodegenerative disorders. We discuss this in the context of glial roles in the homoeostasis and defence of the brain. We consider the mounting evidence supporting a change away from the perception of reactive glial responses merely as secondary detrimental processes that exacerbate the course of neurological disorders, in favour of an emerging contemporary view of glial pathological responses as complex and multistaged defensive processes that also have the potential for dysfunction.

20 Review Dementia with Lewy bodies. 2014

Mayo, Mary Catherine / Bordelon, Yvette. ·Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California. · Movement Disorders Program, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California. ·Semin Neurol · Pubmed #24963677.

ABSTRACT: Dementia with Lewy bodies (DLB) is the second most common diagnosis of dementia after Alzheimer disease (AD). The essential pathologic feature is the Lewy body, a neuronal inclusion containing α-synuclein, found in brainstem nuclei and the neocortex. Clinical features include early fluctuations in attention, hallucinations, and parkinsonism, with progression to a combined cortical and subcortical dementia. To distinguish it from Parkinson disease dementia, a time course of one year from cognitive changes to motor feature onset has been established. There is more severe impairment of verbal fluency, executive function, and visuospatial abilities in DLB patients. Both rapid eye movement sleep behavior disorder and neuroleptic sensitivity are notable in this patient group. Treatment is aimed at symptom management. Cholinesterase inhibitors can be beneficial for behavioral and cognitive issues, whereas dopaminergic agents may help motor symptoms. Survival is equivalent to AD when measured from symptom onset, though diagnosis in DLB may be delayed.

21 Review Pharmacological chaperoning of nAChRs: a therapeutic target for Parkinson's disease. 2014

Srinivasan, Rahul / Henderson, Brandon J / Lester, Henry A / Richards, Christopher I. ·Department of Physiology, University of California Los Angeles, Los Angeles, CA, United States. Electronic address: rahul.srinivasan@gmail.com. · Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, United States. · Department of Chemistry, University of Kentucky, Lexington, KY, United States. ·Pharmacol Res · Pubmed #24593907.

ABSTRACT: Chronic exposure to nicotine results in an upregulation of neuronal nicotinic acetylcholine receptors (nAChRs) at the cellular plasma membrane. nAChR upregulation occurs via nicotine-mediated pharmacological receptor chaperoning and is thought to contribute to the addictive properties of tobacco as well as relapse following smoking cessation. At the subcellular level, pharmacological chaperoning by nicotine and nicotinic ligands causes profound changes in the structure and function of the endoplasmic reticulum (ER), ER exit sites, the Golgi apparatus and secretory vesicles of cells. Chaperoning-induced changes in cell physiology exert an overall inhibitory effect on the ER stress/unfolded protein response. Cell autonomous factors such as the repertoire of nAChR subtypes expressed by neurons and the pharmacological properties of nicotinic ligands (full or partial agonist versus competitive antagonist) govern the efficiency of receptor chaperoning and upregulation. Together, these findings are beginning to pave the way for developing pharmacological chaperones to treat Parkinson's disease and nicotine addiction.

22 Review Mitochondrial dysfunction and oxidative stress in Parkinson's disease. 2013

Subramaniam, Sudhakar Raja / Chesselet, Marie-Francoise. ·Department of Neurology, David Geffen School of Medicine, UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA. ·Prog Neurobiol · Pubmed #23643800.

ABSTRACT: Parkinson's disease (PD) is a movement disorder that is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta resulting in dopamine deficiency in the striatum. Although majority of the PD cases are sporadic several genetic mutations have also been linked to the disease thus providing new opportunities to study the pathology of the illness. Studies in humans and various animal models of PD reveal that mitochondrial dysfunction might be a defect that occurs early in PD pathogenesis and appears to be a widespread feature in both sporadic and monogenic forms of PD. The general mitochondrial abnormalities linked with the disease include mitochondrial electron transport chain impairment, alterations in mitochondrial morphology and dynamics, mitochondrial DNA mutations and anomaly in calcium homeostasis. Mitochondria are vital organelles with multiple functions and their dysfunction can lead to a decline in energy production, generation of reactive oxygen species and induction of stress-induced apoptosis. In this review, we give an outline of mitochondrial functions that are affected in the pathogenesis of sporadic and familial PD, and hence provide insights that might be valuable for focused future research to exploit possible mitochondrial targets for neuroprotective interventions in PD.

23 Review Different diagnostic criteria for Parkinson disease: what are the pitfalls? 2013

Bhidayasiri, Roongroj / Reichmann, Heinz. ·Chulalongkorn Center of Excellence on Parkinson's Disease and Related Disorders, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, 10330, Thailand. rbh1@ucla.edu ·J Neural Transm (Vienna) · Pubmed #23494196.

ABSTRACT: As there are no definite diagnostic tests or reliable biomarkers for Parkinson disease (PD), its diagnosis still relies on the presence of a combination of cardinal motor features, along with the exclusion of other causes of Parkinsonism and the presence of some of supportive features. To date, several diagnostic criteria have been developed for different purposes through expert opinions or comprehensive review of the literature. However, none of them are without limitations. In this article, we review different diagnostic criteria for PD which have been published in the English medical literature, highlighting specific limitations and pitfalls. With considerable progress in the understanding of PD, particularly in a view of diverse clinical symptomatology and its evolution, it will be difficult to establish a single criterion that is capable of capturing all cases at different disease stages. Rather, we should aim to develop a set of criteria which include a consensus on clinical gold standard or reliable biomarkers at different levels of diagnostic certainty for different purposes. Despite a more refined set of criteria that may aid in the recognition of PD, the accuracy of its diagnosis still largely depends on the observational skills and clinical sensitivity of the treating physician.

24 Review Circadian dysfunction may be a key component of the non-motor symptoms of Parkinson's disease: insights from a transgenic mouse model. 2013

Willison, L David / Kudo, Takashi / Loh, Dawn H / Kuljis, Dika / Colwell, Christopher S. ·Division of Child and Adolescent Psychiatry, Laboratory of Circadian and Sleep Medicine, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA. ·Exp Neurol · Pubmed #23353924.

ABSTRACT: Sleep disorders are nearly ubiquitous among patients with Parkinson's disease (PD), and they manifest early in the disease process. While there are a number of possible mechanisms underlying these sleep disturbances, a primary dysfunction of the circadian system should be considered as a contributing factor. Our laboratory's behavioral phenotyping of a well-validated transgenic mouse model of PD reveals that the electrical activity of neurons within the master pacemaker of the circadian system, the suprachiasmatic nuclei (SCN), is already disrupted at the onset of motor symptoms, although the core features of the intrinsic molecular oscillations in the SCN remain functional. Our observations suggest that the fundamental circadian deficit in these mice lies in the signaling output from the SCN, which may be caused by known mechanisms in PD etiology: oxidative stress and mitochondrial disruption. Disruption of the circadian system is expected to have pervasive effects throughout the body and may itself lead to neurological and cardiovascular disorders. In fact, there is much overlap in the non-motor symptoms experienced by PD patients and in the consequences of circadian disruption. This raises the possibility that the sleep and circadian dysfunction experienced by PD patients may not merely be a subsidiary of the motor symptoms, but an integral part of the disease. Furthermore, we speculate that circadian dysfunction can even accelerate the pathology underlying PD. If these hypotheses are correct, more aggressive treatment of the circadian misalignment and sleep disruptions in PD patients early in the pathogenesis of the disease may be powerful positive modulators of disease progression and patient quality of life.

25 Review Drosophila as a model to study mitochondrial dysfunction in Parkinson's disease. 2012

Guo, Ming. ·Department of Neurology, Brain Research Institute, David Geffen School of Medicine, Los Angeles, California 90095, USA. mingfly@ucla.edu ·Cold Spring Harb Perspect Med · Pubmed #23024178.

ABSTRACT: Identification of single gene mutations that lead to inherited forms of Parkinson's disease (PD) has provided strong impetus for the use of animal models to study normal functions of these "PD genes" and the cellular defects that occur in the presence of pathogenic PD mutations. Drosophila has emerged as an effective model in PD-related gene studies. Important insights into the cellular basis of PD pathogenesis include the demonstration that two PD genes, PINK1 and parkin, function in a common pathway, with PINK1 positively regulating parkin, to control mitochondrial integrity and maintenance. This is accomplished through regulation of mitochondrial fission/fusion dynamics. Subsequent observations in both fly and mammalian systems showed that these proteins are important for sensing mitochondrial damage and recruiting damaged mitochondria to the quality-control machinery for subsequent removal. Here, I begin by reviewing the opportunities and challenges to understanding PD pathogenesis and developing new therapies. I then review the unique tools and technologies available in Drosophila for studying PD genes. Subsequently, I review lessons that we have learned from studies in Drosophila, emphasizing the PINK1/parkin pathway, as well as studies of DJ-1 and Omi/HtrA2, two additional genes associated with PD implicated in regulation of mitochondrial function. I end by discussing how Drosophila can be used to further probe the functions of PINK1 and parkin, and the regulation of mitochondrial quality more generally. In additional to PD, defects in mitochondrial function are associated with normal aging and with many diseases of aging. Thus, insights gained from the studies of mitochondrial dynamics and quality control in Drosophila are likely to be of general significance.