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Article: Balancing short-term symptom control and long-term functional outcomes in patients with Parkinson's disease.

Tetrud, James W

2007 Volume 12, Issue 4, Page(s) 275–286

Abstract: Levodopa has played a central role in the treatment of Parkinson's disease for nearly 40 years and remains the single most effective symptomatic treatment for the disease. However, the response to levodopa therapy changes over time, and its long-term use ...

Abstract	Levodopa has played a central role in the treatment of Parkinson's disease for nearly 40 years and remains the single most effective symptomatic treatment for the disease. However, the response to levodopa therapy changes over time, and its long-term use is commonly associated with disabling motor complications. For this reason, the appropriate role of levodopa in the treatment of Parkinson's disease-in particular, the question of when to initiate therapy with the drug-has been a matter of controversy. Because levodopa is the most effective treatment for Parkinson's disease, the management of this disease becomes a matter of balancing short-term symptom control with long-term functional outcomes. This article provides an overview of the basis for levodopa-associated motor complications and their impact on patients' clinical function and quality of life, followed by a discussion of strategies for managing these complications to achieve optimum symptom control while minimizing the adverse effects of long-term therapy.
MeSH term(s)	Activities of Daily Living ; Antiparkinson Agents/administration & dosage ; Antiparkinson Agents/adverse effects ; Dyskinesia, Drug-Induced/diagnosis ; Dyskinesia, Drug-Induced/etiology ; Dyskinesia, Drug-Induced/prevention & control ; Humans ; Levodopa/administration & dosage ; Levodopa/adverse effects ; Long-Term Care ; Parkinson Disease/diagnosis ; Parkinson Disease/drug therapy ; Parkinson Disease/psychology ; Quality of Life ; Risk Factors
Chemical Substances	Antiparkinson Agents ; Levodopa (46627O600J)
Language	English
Publishing date	2007-02-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2008418-3
ISSN	2165-6509 ; 1092-8529
ISSN (online)	2165-6509
ISSN	1092-8529
DOI	10.1017/s1092852900021039
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Article ; Online: MPTP-induced parkinsonism: an historical case series.

Nonnekes, Jorik / Post, Bart / Tetrud, James W / Langston, J William / Bloem, Bastiaan R

The Lancet. Neurology

2018 Volume 17, Issue 4, Page(s) 300–301

MeSH term(s)	Gait/physiology ; History, 20th Century ; Humans ; MPTP Poisoning/diagnosis ; MPTP Poisoning/history ; MPTP Poisoning/physiopathology ; Symptom Assessment ; Tremor/diagnosis ; Tremor/physiopathology
Language	English
Publishing date	2018-03-13
Publishing country	England
Document type	Historical Article ; Letter
ZDB-ID	2079704-7
ISSN	1474-4465 ; 1474-4422
ISSN (online)	1474-4465
ISSN	1474-4422
DOI	10.1016/S1474-4422(18)30072-3
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Article ; Online: A novel formulation of selegiline for the treatment of Parkinson's disease.

Tetrud, James W / Koller, William C

Neurology

2004 Volume 63, Issue 7 Suppl 2, Page(s) S2–6

MeSH term(s)	Absorption ; Administration, Oral ; Antiparkinson Agents/administration & dosage ; Antiparkinson Agents/pharmacokinetics ; Antiparkinson Agents/pharmacology ; Biotransformation ; Forecasting ; Freeze Drying ; Humans ; Monoamine Oxidase Inhibitors/administration & dosage ; Monoamine Oxidase Inhibitors/pharmacokinetics ; Monoamine Oxidase Inhibitors/pharmacology ; Mouth Mucosa/metabolism ; Parkinson Disease/drug therapy ; Randomized Controlled Trials as Topic ; Selegiline/administration & dosage ; Selegiline/pharmacokinetics ; Selegiline/pharmacology ; Solubility ; Tablets ; Treatment Outcome
Chemical Substances	Antiparkinson Agents ; Monoamine Oxidase Inhibitors ; Tablets ; Selegiline (2K1V7GP655)
Language	English
Publishing date	2004-08-05
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Review
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/wnl.63.7_suppl_2.s2
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Article: Genetic fine-mapping of the Iowan

Zafar, Faria / Valappil, Ruksana Azhu / Kim, Sam / Johansen, Krisztina K / Chang, Anne Lynn S / Tetrud, James W / Eis, Peggy S / Hatchwell, Eli / Langston, J William / Dickson, Dennis W / Schüle, Birgitt

NPJ Parkinson's disease

2018 Volume 4, Page(s) 18

Abstract: The "Iowa kindred," a large Iowan family with autosomal-dominant Parkinson's disease, has been followed clinically since the 1920s at the Mayo Clinic. In 2003, the genetic cause was determined to be a 1.7 Mb triplication of the alpha-synuclein genomic ... ...

Abstract	The "Iowa kindred," a large Iowan family with autosomal-dominant Parkinson's disease, has been followed clinically since the 1920s at the Mayo Clinic. In 2003, the genetic cause was determined to be a 1.7 Mb triplication of the alpha-synuclein genomic locus. Affected individuals present with an early-onset, severe parkinsonism-dementia syndrome. Here, we present a descendant of the Iowa kindred with novel, disease-associated non-motor findings of reduced heart rate variability, complete anosmia, and a rare skin condition called colloid milium. At autopsy, key neuropathological findings were compatible with diffuse Lewy body disease. Using high-resolution comparative genomic hybridization (CGH) array analysis to fine-map the genomic breakpoints, we observed two independent recombination events of the
Language	English
Publishing date	2018-06-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2819218-7
ISSN	2373-8057
ISSN	2373-8057
DOI	10.1038/s41531-018-0054-4
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Article ; Online: LRRK2 p.Ile1371Val Mutation in a Case with Neuropathologically Confirmed Multi-System Atrophy.

Lee, Kelsey / Nguyen, Khanh-Dung / Sun, Chao / Liu, Mei / Zafar, Faria / Saetern, Jimmy / Flierl, Adrian / Tetrud, James W / Langston, J William / Dickson, Dennis / Schüle, Birgitt

Journal of Parkinson's disease

2018 Volume 8, Issue 1, Page(s) 93–100

Abstract: Background: Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are among the most common genetic causes of Lewy body Parkinson's disease (PD). However, LRRK2 mutations can also lead to a variety of pathological phenotypes other than typical PD, ... ...

Abstract	Background: Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are among the most common genetic causes of Lewy body Parkinson's disease (PD). However, LRRK2 mutations can also lead to a variety of pathological phenotypes other than typical PD, including relatively pure nigrostriatal cell loss without alpha-synuclein-positive Lewy bodies or Lewy neurites, progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). The mechanisms behind this remarkable pleomorphic pathology are currently unclear. Objective: To genetically and pathologically characterize a case with a LRRK2, p.Ile1371Val rare variant and pathologically proven MSA. Methods: From the brain donation program at the Parkinson's Institute and Clinical Center, we selected 26 brains with family history and a with clinicopathological diagnosis of PD (n = 20), MSA (n = 4), or PSP (n = 2). We performed neuropathological evaluation, including alpha-synuclein and tau immunohistochemistry and sequenced 188 genes that have been reported as causative for or associated with neurodegenerative diseases. Results: We identified a known LRRK2, p.Ile1371Val genetic variant in a case with clinically diagnosed and pathologically proven MSA. Neuropathology revealed that the olivopontocerebellar system was more affected than the striatonigral system. Conclusions: Our data suggest that genetic variants in the LRRK2 gene can present clinically and neuropathologically as MSA. One other LRRK2 genetic variant (LRRK2, p.Ile2020Thr) has been reported with a neuropathological diagnosis of MSA. Interestingly, the LRRK2 variant (LRRK2, p.Ile1371Val) identified here has been reported previously in a postmortem case with Lewy body PD.Future studies are critical to discover the mechanisms leading to different neurodegenerative trajectories both in neuronal and glial cell populations.
MeSH term(s)	Brain/pathology ; Brain Chemistry ; Female ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics ; Middle Aged ; Multiple System Atrophy/genetics ; Multiple System Atrophy/pathology ; Mutation, Missense ; Neuroglia/chemistry ; Neuroglia/ultrastructure ; Neurons/chemistry ; Neurons/ultrastructure ; Pedigree ; Point Mutation ; Sequence Analysis, DNA ; alpha-Synuclein/genetics ; tau Proteins/genetics
Chemical Substances	MAPT protein, human ; alpha-Synuclein ; tau Proteins ; LRRK2 protein, human (EC 2.7.11.1) ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (EC 2.7.11.1)
Language	English
Publishing date	2018-03-01
Publishing country	Netherlands
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2620609-2
ISSN	1877-718X ; 1877-7171
ISSN (online)	1877-718X
ISSN	1877-7171
DOI	10.3233/JPD-171237
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Article ; Online: Mitochondrial dysfunction in skin fibroblasts from a Parkinson's disease patient with an alpha-synuclein triplication.

Mak, Sally K / Tewari, Deepika / Tetrud, James W / Langston, J William / Schüle, Birgitt

Journal of Parkinson's disease

2011 Volume 1, Issue 2, Page(s) 175–183

Abstract: Mitochondrial dysfunction has been frequently implicated in the neurodegenerative process that underlies Parkinson's disease (PD), but the basis for this impairment is not fully understood. The goal of this study was to investigate the effects of α- ... ...

Abstract	Mitochondrial dysfunction has been frequently implicated in the neurodegenerative process that underlies Parkinson's disease (PD), but the basis for this impairment is not fully understood. The goal of this study was to investigate the effects of α-synuclein (α-syn) gene multiplication on mitochondrial function in human tissue. To investigate this question, human fibroblasts were taken from a patient with parkinsonism carrying a triplication in the α-syn gene. Unexpectedly, the cells showed a significant decrease in cell growth compared to matched healthy controls. With regard to mitochondrial function, α-syn triplication fibroblasts exhibited a 39% decrease in ATP production, a 40% reduction in mitochondrial membrane potential, and a 49% reduction in complex I activity. Furthermore, they proved to be more sensitive to the effects of the nigrostrial toxicant paraquat compared to controls. Finally, siRNA knockdown of α-syn resulted in a partial rescue of mitochondrial impairment and reduction of paraquat-induced cell toxicity, suggesting that α-syn plays a causative role for mitochondrial dysfunction in these patient-derived peripheral skin fibroblasts.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Adult ; Cells, Cultured ; Electron Transport Complex I/metabolism ; Female ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/genetics ; Herbicides/pharmacology ; Humans ; Male ; Membrane Potential, Mitochondrial/drug effects ; Membrane Potential, Mitochondrial/genetics ; Middle Aged ; Mitochondrial Diseases/etiology ; Mitochondrial Diseases/genetics ; Mitochondrial Diseases/pathology ; Paraquat/pharmacology ; Parkinson Disease/complications ; Parkinson Disease/genetics ; Parkinson Disease/pathology ; RNA, Messenger/metabolism ; RNA, Small Interfering/pharmacology ; Skin/pathology ; alpha-Synuclein/genetics
Chemical Substances	Herbicides ; RNA, Messenger ; RNA, Small Interfering ; alpha-Synuclein ; Adenosine Triphosphate (8L70Q75FXE) ; Electron Transport Complex I (EC 1.6.5.3) ; Paraquat (PLG39H7695)
Language	English
Publishing date	2011
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2620609-2
ISSN	1877-718X ; 1877-7171
ISSN (online)	1877-718X
ISSN	1877-7171
DOI	10.3233/JPD-2011-11025
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Article: Neurodegenerative disorders mimicking progressive supranuclear palsy: a report of three cases.

Murphy, Marjorie A / Friedman, Joseph H / Tetrud, James W / Factor, Stewart A

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia

2005 Volume 12, Issue 8, Page(s) 941–945

Abstract: Progressive supranuclear palsy (PSP) is rarely confused with other parkinsonian disorders once the vertical gaze palsy appears. Corticobasal degeneration is the most common differential diagnostic entity. We describe three cases diagnosed during life as ... ...

Abstract	Progressive supranuclear palsy (PSP) is rarely confused with other parkinsonian disorders once the vertical gaze palsy appears. Corticobasal degeneration is the most common differential diagnostic entity. We describe three cases diagnosed during life as PSP but found to have another neurologic disorder at autopsy. No explanation for the gaze palsies was found in any case.
MeSH term(s)	Aged ; Brain/pathology ; Diagnosis, Differential ; Female ; Humans ; Male ; Neurodegenerative Diseases/pathology ; Neurodegenerative Diseases/physiopathology ; Ocular Motility Disorders/etiology ; Supranuclear Palsy, Progressive/pathology ; Supranuclear Palsy, Progressive/physiopathology
Language	English
Publishing date	2005-11
Publishing country	Scotland
Document type	Case Reports ; Journal Article
ZDB-ID	1193674-5
ISSN	0967-5868
ISSN	0967-5868
DOI	10.1016/j.jocn.2004.10.013
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Article: Voluntarily simulated tremor in normal subjects.

Burkhard, Pierre R / Langston, J William / Tetrud, James W

Neurophysiologie clinique = Clinical neurophysiology

2002 Volume 32, Issue 2, Page(s) 119–126

Abstract: Based on the hypothesis that rhythmical, tremor-like movements produced by normal subjects might be influenced by similar central oscillatory neuronal networks believed to determine the features of the pathologic tremors of Parkinson's disease (PD) or ... ...

Abstract	Based on the hypothesis that rhythmical, tremor-like movements produced by normal subjects might be influenced by similar central oscillatory neuronal networks believed to determine the features of the pathologic tremors of Parkinson's disease (PD) or Essential Tremor (ET) patients, we examined the neurophysiological characteristics of a tremor mimicked by normal volunteers and compare this data with those from PD or ET tremors. Voluntarily simulated tremor (VST) was studied in 47 neurologically intact subjects, resting tremor in 10 patients with PD and postural tremor in 10 patients with ET. Using a tremor analysis system based on a solid state gyroscopic sensor sensitive to angular rate, the following parameters were determined: frequency, amplitude (angular displacement) and regularity (Q coefficient of constancy). We also performed an inertial loading test and a test-retest analysis. Nearly all normal subjects were able to simulate a tremor that was indistinguishable, in frequency and regularity, from that of PD or ET, although the amplitude was significantly higher in normal subjects. As in pathological tremors, the VST frequency was significantly influenced by age, but not by gender, handedness or previous knowledge of tremor. Inertial load did not modify the tremor frequency, suggesting that mechanical factors were minor. We also found a logarithmic inverse relationship between frequency and amplitude of the VST. We concluded that VST shares many similarities with pathological tremors. It is therefore possible that all tremors are somehow influenced by the same central oscillators which may become disinhibited and clinically apparent in pathological conditions such as PD or ET.
MeSH term(s)	Aged ; Aged, 80 and over ; Aging/physiology ; Electrophysiology ; Female ; Humans ; Male ; Middle Aged ; Nerve Net/physiology ; Parkinson Disease/physiopathology ; Tremor/physiopathology
Language	English
Publishing date	2002-05-21
Publishing country	France
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639421-8
ISSN	1769-7131 ; 0987-7053
ISSN (online)	1769-7131
ISSN	0987-7053
DOI	10.1016/s0987-7053(02)00296-4
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Article ; Online: Tolerability and efficacy of switching from oral selegiline to Zydis selegiline in patients with Parkinson's disease.

Ondo, William G / Hunter, Christine / Isaacson, Stuart H / Silver, Dee E / Stewart, R Malcolm / Tetrud, James W / Davidson, Anthony

Parkinsonism & related disorders

2011 Volume 17, Issue 2, Page(s) 117–118

Abstract: Selegiline is a monoamine-B specific inhibitor used to treat Parkinson's disease. A Zydis sublingual preparation has more efficient absorption and less first pass amphetamine metabolites. We conducted an open label oral to Zydis switch study to evaluate ... ...

Abstract	Selegiline is a monoamine-B specific inhibitor used to treat Parkinson's disease. A Zydis sublingual preparation has more efficient absorption and less first pass amphetamine metabolites. We conducted an open label oral to Zydis switch study to evaluate tolerability of rapid switch, and relative efficacy, in 48 subjects from 5 sites. Overall patients preferred the Zydis preparation. Per clinician global impressions, fluctuations improved and the "on" UPDRS part II scores improved. Total UPDRS and measures of fatigue and sleep were unchanged. Adverse events were mild. Patients generally preferred the Zydis selegiline preparation but the modest difference is of unclear clinical significance given the open label nature of the trial.
MeSH term(s)	Administration, Oral ; Administration, Sublingual ; Aged ; Chemistry, Pharmaceutical ; Drug Substitution/methods ; Female ; Follow-Up Studies ; Humans ; Male ; Parkinson Disease/drug therapy ; Parkinson Disease/metabolism ; Selegiline/administration & dosage ; Selegiline/adverse effects ; Treatment Outcome
Chemical Substances	Selegiline (2K1V7GP655)
Language	English
Publishing date	2011-02
Publishing country	England
Document type	Clinical Trial ; Comparative Study ; Journal Article ; Multicenter Study
ZDB-ID	1311489-x
ISSN	1873-5126 ; 1353-8020
ISSN (online)	1873-5126
ISSN	1353-8020
DOI	10.1016/j.parkreldis.2010.10.001
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Zs.A 4553: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 420: Show issues

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Article ; Online: Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces "off" time in Parkinson's disease: a double-blind, randomized, multicenter clinical trial (6002-US-005).

LeWitt, Peter A / Guttman, M / Tetrud, James W / Tuite, Paul J / Mori, Akihisa / Chaikin, Philip / Sussman, Neil M

Annals of neurology

2008 Volume 63, Issue 3, Page(s) 295–302

Abstract: Objective: Based on new understanding of nondopaminergic pathways involved in Parkinson's disease (PD) pathophysiology, a selective adenosine A(2A) receptor antagonist, istradefylline, shows promise for the treatment of PD.: Methods: Istradefylline ( ... ...

Abstract	Objective: Based on new understanding of nondopaminergic pathways involved in Parkinson's disease (PD) pathophysiology, a selective adenosine A(2A) receptor antagonist, istradefylline, shows promise for the treatment of PD. Methods: Istradefylline (40mg/day) was studied in levodopa-treated PD subjects experiencing prominent wearing-off motor fluctuations. At 23 North American sites, 196 subjects were randomized in a double-blind, 12-week outpatient clinical trial of istradefylline (114 completing the trial) or placebo (58 completing the trial). The primary efficacy measure was change from baseline to end point in the percentage of daily awake "off" time, recorded by subjects using a patient PD diary. Secondary end points evaluated "on" time (including "on time with dyskinesia"), the Unified Parkinson's Disease Rating Scale, and a Clinical Global Impression-Improvement of Illness score. Clinical laboratory, electrocardiograms, vital signs, and adverse event monitoring comprised the safety monitoring. Results: After randomization, approximately 88% of subjects completed the double-blind period. Compared with baseline, the decrease of daily awake "off" time for istradefylline was a mean (+/- standard deviation) of -10.8 +/- 16.6% (95% confidence interval, -13.46 to -7.52) and for placebo, -4.0 +/- 15.7% (95% confidence interval, -7.73-0.31; p = 0.007 using two-way analysis of variance). This effect corresponded to changes from baseline in total daily awake "off" time of -1.8 +/- 2.8 hours for istradefylline and -0.6 +/- 2.7 hours for placebo (p = 0.005). Treatment-emergent adverse effects with istradefylline were generally mild. Interpretation: Istradefylline was safe, well tolerated, and offered a clinically meaningful reduction in "off" time without increased troublesome dyskinesia.
MeSH term(s)	Adenosine A2 Receptor Antagonists ; Aged ; Antiparkinson Agents/therapeutic use ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/drug therapy ; Parkinson Disease/physiopathology ; Purines/therapeutic use ; Receptor, Adenosine A2A/physiology
Chemical Substances	Adenosine A2 Receptor Antagonists ; Antiparkinson Agents ; Purines ; Receptor, Adenosine A2A ; istradefylline (2GZ0LIK7T4)
Language	English
Publishing date	2008-03
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	80362-5
ISSN	1531-8249 ; 0364-5134
ISSN (online)	1531-8249
ISSN	0364-5134
DOI	10.1002/ana.21315
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Zs.MO 478: Show issues

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