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ABSTRACT: The objective of this study was to confirm whether an association between handedness and the side of symptom onset exists and to evaluate the impact of this association on specific clinical characteristics of Parkinson's disease (PD).
1173 PD patients were identified from a clinical database. Patients with asymmetrical onset (n=1015) were divided into those with dominant-side onset and those with non-dominant-side onset, and the clinical characteristics of the two subgroups were compared.
In our PD sample, 86.5% of patients presented asymmetrically. There was a significant association between handedness and the side of the initial symptom; that is, the dominant side was affected first in the majority of both left- and right-handed patients. Compared with patients with non-dominant side onset, more patients with dominant-side onset presented with bradykinesia, while fewer patients presented with gait difficulty. Patients with dominant-side onset were diagnosed and began dopaminergic medication after a longer symptom duration than patients with non-dominant-side onset. The only difference in Unified Parkinson Disease Rating Scale scores between the two groups was in a subscore addressing dominant-hand tasks.
An association exists between the dominant hand and the side of the initial motor symptom in PD. Whether the initial symptom occurs on the dominant or non-dominant side has implications for the reported first symptom, the time to diagnosis and the time to dopaminergic treatment initiation. The side of disease onset does not affect the severity of disease, as measured by the Unified Parkinson Disease Rating Scale.
Journal of neurology, neurosurgery, and psychiatry 10/2011; 82(10):1122-4. · 4.87 Impact Factor
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ABSTRACT: Risk-taking behavior is characterized by pursuit of reward in spite of potential negative consequences. Dopamine neurotransmission along the mesocorticolimbic pathway is a potential modulator of risk behavior. In patients with Parkinson's disease (PD), impulse control disorder (ICD) can result from dopaminergic medication use, particularly dopamine agonists (DAA). Behaviors associated with ICD include hypersexuality as well as compulsive gambling, shopping, and eating, and these behaviors are potentially linked to alterations to risk processing. Using the Balloon Analogue Risk Task, we assessed the role of agonist therapy on risk-taking behavior in PD patients with (n = 22) and without (n = 19) active ICD symptoms. Patients performed the task both "on" and "off" DAA. DAA increased risk-taking in PD patients with active ICD symptoms, but it did not affect risk behavior of PD controls. DAA dose was also important in explaining risk behavior. Both groups similarly reduced their risk-taking in high compared to low risk conditions and following the occurrence of a negative consequence, suggesting that ICD patients do not necessarily differ in their abilities to process and adjust to some aspects of negative consequences. Our findings suggest dopaminergic augmentation of risk-taking behavior as a potential contributing mechanism for the emergence of ICD in PD patients.
Behavioral Neuroscience 05/2011; 125(4):492-500. · 2.62 Impact Factor
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Muscle & Nerve 10/2009; 41(1):148-50. · 2.37 Impact Factor
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ABSTRACT: The activities of daily living (ADL) subscore of the Unified Parkinson's Disease Rating Scale (UPDRS) captures the impact of Parkinson's disease (PD) on daily function and may be less affected than other subsections by variability associated with drug cycle and motor fluctuations. We examined UPDRS mentation, ADL and motor subscores in 888 patients with idiopathic PD. Multiple linear regression analyses determined the association between disease duration and UPDRS subscores as a function of medication status at examination and in a subset of patients with multiple examinations. Independent of medication status and across cross-sectional and longitudinal analyses, ADL subscores showed a stronger and more stable association with disease duration than other UPDRS subscores after adjusting for age of disease onset. The association between disease duration and the motor subscore depended on medication status. The strong association between ADL subscore and disease duration in PD suggests that this measure may serve as a better marker of disease progression than signs and symptoms assessed in other UPDRS sections.
Movement Disorders 11/2008; 24(2):224-30. · 4.51 Impact Factor
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Christopher F McNicoll,
Jeanne C Latourelle,
Marcy E MacDonald,
Mark F Lew,
Oksana Suchowersky,
Christine Klein,
Lawrence I Golbe,
Margery H Mark,
John H Growdon, G Frederick Wooten, [......],
Jomana Al-Hinti,
Anette T Moller,
Karen Ostergaard,
Scott J Sherman,
Richard Roxburgh,
Barry Snow,
John T Slevin,
Franca Cambi,
James F Gusella,
Richard H Myers
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ABSTRACT: The ATP/ADP ratio reflects mitochondrial function and has been reported to be influenced by the size of the Huntington disease gene (HD) repeat. Impaired mitochondrial function has long been implicated in the pathogenesis of Parkinson's disease (PD), and therefore, we evaluated the relationship of the HD CAG repeat size to PD onset age in a large sample of familial PD cases. PD affected siblings (n = 495), with known onset ages from 248 families, were genotyped for the HD CAG repeat. Genotyping failed in 11 cases leaving 484 for analysis, including 35 LRRK2 carriers. All cases had HD CAG repeats (range, 15-34) below the clinical range for HD, although 5.2% of the sample (n = 25) had repeats in the intermediate range (the intermediate range lower limit = 27; upper limit = 35 repeats), suggesting that the prevalence of intermediate allele carriers in the general population is significant. No relation between the HD CAG repeat size and the age at onset for PD was found in this sample of familial PD.
Movement Disorders 08/2008; 23(11):1596-601. · 4.51 Impact Factor
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ABSTRACT: The unified Parkinson's disease rating scale (UPDRS) is the most widely used tool to rate the severity and the stage of Parkinson's disease (PD). However, the mentation, behavior and mood (MBM) subscale of the UPDRS has received little investigation regarding its validity and sensitivity. Three items of this subscale were compared to criterion tests to examine validity, sensitivity and specificity.
Ninety-seven patients with idiopathic PD were assessed on the UPDRS. Scores on three items of the MBM subscale, intellectual impairment, thought disorder and depression, were compared to criterion tests, the telephone interview for cognition status (TICS), psychiatric assessment for psychosis and the geriatric depression scale (GDS). Non-parametric tests of association were performed to examine concurrent validity of the MBM items. The sensitivities, specificities and optimal cutoff scores for each MBM item were estimated by receiver operating characteristic (ROC) curve analysis.
The MBM items demonstrated low to moderate correlation with the criterion tests, and the sensitivity and specificity were not strong. Even using a score of 7.0 on the items of the MBM demonstrated a sensitivity/specificity of only 0.19/0.48 for intellectual impairment, 0.60/0.72 for thought disorder and 0.61/0.87 for depression. Using a more appropriate cutoff of 2.0 revealed sensitivities of 0.01, 0.38 and 0.13 respectively.
The MBM subscale items of intellectual impairment, thought disorder and depression are not appropriate for screening or diagnostic purposes. Tools such as the TICS and the GDS should be considered instead.
Neurological Research 08/2008; 30(5):493-6. · 1.52 Impact Factor
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Mei Sun,
Jeanne C Latourelle, G Frederick Wooten,
Mark F Lew,
Christine Klein,
Holly A Shill,
Lawrence I Golbe,
Margery H Mark,
Brad A Racette,
Joel S Perlmutter, [......],
Peter P Pramstaller,
David J Burn,
Patrick F Chinnery,
Scott Sherman,
Peter Vieregge,
Irene Litvan,
Tammy Gillis,
Marcy E MacDonald,
Richard H Myers,
James F Gusella
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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 sample 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.
Archives of Neurology 07/2006; 63(6):826-32. · 7.58 Impact Factor
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Anthony E Lang,
J William Langston,
A Jon Stoessl,
Matthew Brodsky,
David J Brooks,
Vijay Dhawan,
William J Elias,
Andres M Lozano,
Elena Moro,
John G Nutt,
Mark Stacy,
Dennis Turner, G Frederick Wooten
The Lancet Neurology 04/2006; 5(3):200-2. · 23.46 Impact Factor
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ABSTRACT: Using functional magnetic resonance imaging (fMRI), the authors examined visual cortex function in Parkinson's disease patients who did and did not experience visual hallucinations. Patients with visual hallucinations demonstrated increased activation in the visual association cortex and deficits in the primary visual cortex, suggesting that visual hallucinations are associated with an abnormality of visual-cortex function.
Journal of Neuropsychiatry 02/2006; 18(3):402-4. · 2.51 Impact Factor
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New England Journal of Medicine 10/2005; 353(10):1021-7. · 53.30 Impact Factor
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ABSTRACT: Depression was diagnosed in 15% of 100 consecutive patients with Parkinson disease (PD). Depression was associated with lower cognition, history of depression, and a higher Unified Parkinson's Disease Rating Scale score. The latter was due to differences in the activities of daily living (ADL) subscale (17 +/- 7 vs 12 +/- 6; p = 0.004) rather than the motor subscale (30 +/- 13 vs 26 +/- 13; p = 0.27). These results suggest that ADL impairment may in part be due to depression. Patients with PD with poor function should be closely evaluated for depression.
Neurology 07/2005; 64(12):2134-5. · 8.31 Impact Factor
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ABSTRACT: Attention deficit-hyperactivity disorder (ADHD) is treated frequently with stimulants in both children and adults. While tics are occasional complications of stimulant therapy, chorea is reported rarely. We describe an adult ADHD patient who developed chorea upon dose escalation of mixed amphetamine salts, which resolved on discontinuation of the drug.
Movement Disorders 08/2004; 19(7):840-2. · 4.51 Impact Factor
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ABSTRACT: Although estrogen therapy has been associated with improved cognitive functioning, a reduced risk of dementia in women with Parkinson disease (PD), and a decreased risk of Alzheimer disease, estrogen therapy has not affected the risk of PD per se.
To determine whether postmenopausal women with PD differed from control subjects with regard to estrogen exposure.Design, Setting, and Patients A case-control design was used, abstracting questionnaire data obtained via interview from 133 female PD cases and 128 female controls during routine outpatient clinic visits in 1999 at a mid-Atlantic tertiary care referral center. There were 140 subjects (68 PD cases and 72 controls) who met the inclusion criteria. Main Outcome Measure Use of postmenopausal estrogen therapy.
More women in the control group than in the PD group took postmenopausal estrogen (36 [50%] of 72 women vs 17 [25%] of 68 women; P<.003), and women who had taken postmenopausal estrogen were less likely to develop PD than those who had not (odds ratio, 0.40 [95% confidence interval, 0.19-0.84]; P<.02). Among PD cases only, postmenopausal estrogen use was not associated with age of onset.
Postmenopausal estrogen therapy may be associated with a reduced risk of PD in women.
Archives of Neurology 07/2004; 61(6):886-8. · 7.58 Impact Factor
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Advances in neurology 02/2004; 94:147-54.
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Anita L DeStefano,
Mark F Lew,
Lawrence I Golbe,
Margery H Mark,
Alice M Lazzarini,
Mark Guttman,
Erwin Montgomery,
Cheryl H Waters,
Carlos Singer,
Ray L Watts, [......],
John H Growdon,
Peter Vieregge,
Peter P Pramstaller,
Christine Klein,
Jean P Hubble,
Carson R Reider,
Mark Stacy,
Marcy E MacDonald,
James F Gusella,
Richard H Myers
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ABSTRACT: Parkinson disease (PD) is a late-onset neurodegenerative disorder. The mean age at onset is 61 years, but the disease can range from juvenile cases to cases in the 8th or 9th decade of life. The parkin gene on chromosome 6q and loci on chromosome 1p35-36 and 1p36 are responsible for some cases of autosomal recessive early-onset parkinsonism, but they do not appear to influence susceptibility or variability of age at onset for idiopathic PD. We have performed a genomewide linkage analysis using variance-component methodology to identify genes influencing age at onset of PD in a population of affected relatives (mainly affected sibling pairs) participating in the GenePD study. Four chromosomal loci showed suggestive evidence of linkage: chromosome 2p (maximum multipoint LOD [MaxLOD] = 2.08), chromosome 9q (MaxLOD = 2.00), chromosome 20 (MaxLOD = 1.82), and chromosome 21 (MaxLOD = 2.21). The 2p and 9q locations that we report here have previously been reported as loci influencing PD affection status. Association between PD age at onset and allele 174 of marker D2S1394, located on 2p13, was observed in the GenePD sample (P=.02). This 174 allele is common to the PD haplotype observed in two families that show linkage to PARK3 and have autosomal dominant PD, which suggests that this allele may be in linkage disequilibrium with a mutation influencing PD susceptibility or age at onset of PD.
The American Journal of Human Genetics 06/2002; 70(5):1089-95. · 10.60 Impact Factor
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ABSTRACT: Sex-linked male deafness and dystonia (Mohr-Tranebjaerg syndrome) arises from mutation of the deafness/dystonia peptide (DDP) gene. We describe a novel guanine deletion at nucleotide 108 of the DDP gene in a family with Mohr-Tranebjaerg syndrome, which terminates this 97–amino acid protein at codon 25. Unlike previously reported kindreds, carrier females in this family also manifest dystonias, including torticollis and writer's cramp. A family history of male deafness should alert clinicians to the possibility of DDP mutation in women with focal dystonias.
Annals of Neurology 09/2001; 50(4):537 - 540. · 11.09 Impact Factor
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ABSTRACT: In vitro quantitative autoradiography with [3H]MK-801 was used to determine Kd and Bmax values for the NMDA receptor-coupled channel in subregions of the rat hippocampal formation. A single form of the channel with an apparent Kd in the 15–20 nM range was found for [3H]MK-801 binding in the presence of both 1μM glutamate and 1μM glycine. Specific binding was highest in the molecular layer of the dentate gyrus, followed by CA1 stratum radiatum and CA1 stratum oriens. Fewer binding sites were observed in the hilus of the dentate gyrus, cerebral cortex, CA1 stratum pyramidale. CA3 subregion (stratum oriens, stratum pyramidale, stratum radiatum), and thalamus. Selective destruction of dentate granule cells by colchicine microinjections reduced the amount of specific [3H]MK-801 binding by half in the molecular layer of the dentate, compared to intact tissue. [3H]MK-801 binding did not change in other hippocampal subregions as a consequence of colchicine injection. Electrolytic entorhinal cortical lesions produced no changes in regional MK-801 binding site density in any of the regions under study. To address the tissue shrinkage following entorhinal cortex lesions, detailed analysis of the binding site density per fixed (16 μm) length of granule cell dendrite, and of the aggregate density across the entire molecular layer revealed no change in the number of MK-801 binding sites per unit length of dendrite in the molecular layer of the dentate gyrus. These findings indicate that NMDA receptor-coupled channels are confined to a postsynaptic location in the perforant path-dentate granule cell system of the adult rat.
Brain Research 05/1990; · 2.73 Impact Factor
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ABSTRACT: We have used the suicide transport agent volkensin to produce selective lesions of striatonigral neurons. By in situ hybridization histochemistry unilateral volkensin injections in the substantia nigra decreased the number of D1 receptor mRNA-expressing neurons in the ipsilateral striatum but did not change the number of D2 receptor and A2a adenosine receptor mRNA-expressing neurons. These findings confirm that striatonigral neurons express D1 receptors and suggest that D2-A2a receptor expressing neurons are predominantly localized to other neuronal populations within the striatum.
Brain Research.
