ORCID Profile
0000-0002-3485-3445
Current Organisation
University of California, San Diego
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Publisher: Oxford University Press (OUP)
Date: 05-2007
Publisher: Springer Science and Business Media LLC
Date: 05-11-2008
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-05-2008
Publisher: American Medical Association (AMA)
Date: 05-2014
DOI: 10.1001/JAMANEUROL.2014.131
Abstract: Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. To examine whether CoQ10 could slow disease progression in early PD. A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity a modified Hoehn and Yahr stage of 2.5 or less and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10 all participants received 1200 IU/d of vitamin E. Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10 P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10 P = .21 relative to placebo). Coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit. clinicaltrials.gov Identifier: NCT00740714.
Publisher: Elsevier BV
Date: 12-2009
Publisher: Oxford University Press (OUP)
Date: 04-2007
Publisher: Springer Science and Business Media LLC
Date: 16-06-2015
DOI: 10.1038/NCOMMS8247
Abstract: Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases ( n =152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT ( P =1.42 × 10 −12 ), 8p12 at lnc-KIF13B-1 , a long non-coding RNA (rs643472 P =3.41 × 10 −8 ), and 2p22 at SOS1 (rs963731 P =1.76 × 10 −7 ). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22 rs1768208 P =2.07 × 10 −7 ) and MAPT H1c (17q21 rs242557 P =7.91 × 10 −6 ). We previously reported SNP/transcript level associations with rs8070723/ MAPT , rs242557/ MAPT , and rs1768208/ MOBP and herein identified association with rs963731/ SOS1 . We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein).
Publisher: Wiley
Date: 10-2015
DOI: 10.1002/MDS.26424
Abstract: This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical diagnosis the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise in PD diagnosis. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies on three categories of diagnostic features: absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of the PD diagnosis). Two levels of certainty are delineated: clinically established PD (maximizing specificity at the expense of reduced sensitivity) and probable PD (which balances sensitivity and specificity). The Movement Disorder Society criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, the Movement Disorder Society criteria will need continuous revision to accommodate these advances.
Publisher: Springer Science and Business Media LLC
Date: 22-09-2009
Abstract: Age at onset in Parkinson disease (PD) is a highly heritable quantitative trait for which a significant genetic influence is supported by multiple segregation analyses. Because genes associated with onset age may represent invaluable therapeutic targets to delay the disease, we sought to identify such genetic modifiers using a genomewide association study in familial PD. There have been previous genomewide association studies (GWAS) to identify genes influencing PD susceptibility, but this is the first to identify genes contributing to the variation in onset age. Initial analyses were performed using genotypes generated with the Illumina HumanCNV370Duo array in a s le of 857 unrelated, familial PD cases. Subsequently, a meta-analysis of imputed SNPs was performed combining the familial PD data with that from a previous GWAS of 440 idiopathic PD cases. The SNPs from the meta-analysis with the lowest p-values and consistency in the direction of effect for onset age were then genotyped in a replication s le of 747 idiopathic PD cases from the Parkinson Institute Biobank of Milan, Italy. Meta-analysis across the three studies detected consistent association (p 1 × 10 -5 ) with five SNPs, none of which reached genomewide significance. On chromosome 11, the SNP with the lowest p-value (rs10767971 p = 5.4 × 10 -7 ) lies between the genes QSER1 and PRRG4 . Near the PARK3 linkage region on chromosome 2p13, association was observed with a SNP (rs7577851 p = 8.7 × 10 -6 ) which lies in an intron of the AAK1 gene. This gene is closely related to GAK , identified as a possible PD susceptibility gene in the GWAS of the familial PD cases. Taken together, these results suggest an influence of genes involved in endocytosis and lysosomal sorting in PD pathogenesis.
Publisher: American Medical Association (AMA)
Date: 06-2006
DOI: 10.1001/ARCHNEUR.63.6.826
Abstract: The PARK2 gene at 6q26 encodes parkin, whose inactivation is implicated in an early-onset autosomal recessive form of Parkinson disease (PD). To evaluate the influence of heterozygosity for parkin mutation on onset age in a s le of families with at least 2 PD-affected members. Clinical and genetic study. Twenty collaborative clinical sites. Patients with familial PD collected in the GenePD study. Studied families were selected for (1) affected sibling pairs sharing 2 alleles identical by state at PARK2 (D6S305) or (2) 1 or more family members with onset age younger than 54 years, regardless of D6S305 status. At least 1 member from each of 183 families underwent comprehensive screening for deletion/insertion variants and point mutations in PARK2. Mutations in the parkin gene were screened by means of single-stranded conformation polymorphism and sequencing in all 12 coding exons and flanking intronic sequences for point mutations and duplex quantitative polymerase chain reaction in all exons for rearrangement, duplication, and deletion. Mutations were found in 23 families (12.6% of those screened). Among the mutation-positive families, 10 (43%) contained compound heterozygotes 3 (13%), homozygotes and 10 (43%), heterozygotes. The onset age in patients with parkin gene mutations ranged from 20 to 76 years. Patients with 1 parkin mutation had an 11.7-year age at onset than did patients with none (P = .04), and patients with 2 or more parkin mutations had a 13.2-year decrease in age at onset compared with patients with 1 mutation (P = .04). These data indicate that parkin mutations are not rare in multiply affected sibships, and that heterozygous mutation carrier status in PARK2 significantly influences age at onset of PD.
Publisher: Elsevier BV
Date: 03-1998
Publisher: Wiley
Date: 10-2016
DOI: 10.1002/MDS.26694
Publisher: Wiley
Date: 10-2015
DOI: 10.1002/MDS.26431
Abstract: This article describes research criteria and probability methodology for the diagnosis of prodromal PD. Prodromal disease refers to the stage wherein early symptoms or signs of PD neurodegeneration are present, but classic clinical diagnosis based on fully evolved motor parkinsonism is not yet possible. Given the lack of clear neuroprotective/disease-modifying therapy for prodromal PD, these criteria were developed for research purposes only. The criteria are based upon the likelihood of prodromal disease being present with probable prodromal PD defined as ≥80% certainty. Certainty estimates rely upon calculation of an in idual's risk of having prodromal PD, using a Bayesian naïve classifier. In this methodology, a previous probability of prodromal disease is delineated based upon age. Then, the probability of prodromal PD is calculated by adding diagnostic information, expressed as likelihood ratios. This diagnostic information combines estimates of background risk (from environmental risk factors and genetic findings) and results of diagnostic marker testing. In order to be included, diagnostic markers had to have prospective evidence documenting ability to predict clinical PD. They include motor and nonmotor clinical symptoms, clinical signs, and ancillary diagnostic tests. These criteria represent a first step in the formal delineation of early stages of PD and will require constant updating as more information becomes available.
Publisher: Wiley
Date: 26-09-2016
DOI: 10.1002/MDS.26796
Publisher: Elsevier BV
Date: 05-2016
Publisher: Wiley
Date: 04-03-2015
DOI: 10.1002/MDS.26170
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-10-2005
DOI: 10.1212/01.WNL.0000187889.17253.B1
Abstract: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each in idual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in approximately 50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.
Publisher: Wiley
Date: 11-03-2014
DOI: 10.1002/MDS.25844
Publisher: Public Library of Science (PLoS)
Date: 02-08-2011
Publisher: Elsevier BV
Date: 04-2007
DOI: 10.1086/513320
Publisher: Wiley
Date: 03-2012
DOI: 10.1002/ANA.22687
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 26-12-2006
Publisher: Wiley
Date: 13-05-2017
DOI: 10.1002/MDS.27034
Publisher: Springer Science and Business Media LLC
Date: 09-2014
DOI: 10.1038/NG.3043
Publisher: Wiley
Date: 22-07-2008
DOI: 10.1002/MDS.22186
Publisher: Springer Science and Business Media LLC
Date: 29-06-2008
Publisher: Springer Science and Business Media LLC
Date: 19-06-2011
DOI: 10.1038/NG.859
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-12-2005
Location: United States of America
No related grants have been discovered for Irene Litvan.