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1.  Parkinsonism in patients with a history of amphetamine exposure 
We recently found a higher rate of prolonged amphetamine exposure in patients diagnosed with Parkinson's disease (PD) than in spouse/caregiver controls. Since distinguishing features have been described in some patients with parkinsonism due to environment exposures (e.g. manganese), we sought to compare the clinical features of PD patients with prolonged amphetamine exposure with unexposed PD patients. Prolonged exposure was defined as a minimum of twice a week for ≥ 3 months, or weekly use ≥ 1 year. We reviewed the clinical records of patients with PD who had participated in a telephone survey of drug and environmental exposures and compared the clinical features of patients with a history of prolonged amphetamine exposure to patients who had no such exposure. Records were available for 16 of 17 (94%) patients with prior amphetamine exposure and 127 of 137 (92%) of those unexposed. Age at diagnosis was younger in the amphetamine-exposed group (49.8 ± 8.2 years vs. 53.1 ±7.4 years; p < 0.05), but other features, including presenting symptoms, initial and later treatments, development of motor fluctuations, and MRI findings were similar between these groups. Because we did not detect clinical features that differentiate parkinsonism in patients with prolonged amphetamine exposure, research to determine whether amphetamine exposure is a risk factor for parkinsonism will require detailed histories of medication and recreational drug use.
PMCID: PMC2831101  PMID: 20063432
neurotoxin; selective vulnerability; neurotoxicant
2.  The neurophysiology and effect of deep brain stimulation in a human with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -induced parkinsonism 
Journal of neurosurgery  2009;110(2):234-238.
Parkinsonism caused by MPTP exposure was first identified in intravenous drug users. The neurotoxicant has since been used extensively in nonhuman primates to induce an experimental model of Parkinson’s disease. We examined the intraoperative physiology and the efficacy of subthalamic nucleus deep brain stimulation (DBS) in 1 of only 4 known living humans with MPTP-induced parkinsonism. The physiologic recordings were consistent with recordings from MPTP-treated primates and humans with Parkinson’s disease, thus further validating the MPTP model for the study of the neurophysiology of the nigrostriatal dopaminergic deficit in Parkinson’s disease. Furthermore, DBS offered significant clinical improvement in this patient similar to that seen in idiopathic Parkinson’s disease. This unique case has important implications for translational research that employs the MPTP-primate model for symptomatic therapy in Parkinson’s disease.
PMCID: PMC2908499  PMID: 19099380
Parkinson’s disease; toxin; parkinsonism; Parkinsonian; deep brain stimulation; subthalamic nucleus; physiology
3.  No Sex Differences in Use of Dopaminergic Medication in Early Parkinson Disease in the US and Canada - Baseline Findings of a Multicenter Trial 
PLoS ONE  2014;9(12):e112287.
Sex differences in Parkinson disease clinical features have been reported, but few studies have examined sex influences on use of dopaminergic medication in early Parkinson disease. The objective of this study was to test if there are differences in the type of dopaminergic medication used and levodopa equivalent daily dose between men and women with early Parkinson disease enrolled in a large multicenter study of Creatine as a potential disease modifying therapy – the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease Long-Term Study-1.
Baseline data of 1,741 participants from 45 participating sites were analyzed. Participants from the United States and Canada were enrolled within five years of Parkinson Disease diagnosis. Two outcome variables were studied: type of dopaminergic medication used and levodopa equivalent daily dose at baseline in the Long-Term Study-1. Chi-square statistic and linear regression models were used for statistical analysis.
There were no statistically significant differences in the frequency of use of different types of dopaminergic medications at baseline between men and women with Parkinson Disease. A small but statistically significant difference was observed in the median unadjusted levodopa equivalent daily dose at baseline between women (300 mg) and men (325 mg), but this was not observed after controlling for disease duration (years since Parkinson disease diagnosis), disease severity (Unified Parkinson's Disease Rating Scale Motor and Activities of Daily Living Scores), and body weight.
In this large multicenter study, we did not observe sex differences in the type and dose of dopaminergic medications used in early Parkinson Disease. Further research is needed to evaluate the influence of male or female sex on use of dopaminergic medication in mid- and late-stage Parkinson Disease.
PMCID: PMC4259292  PMID: 25486269
4.  Hospitalization in Parkinson disease: A survey of National Parkinson Foundation Centers☆ 
Parkinsonism & related disorders  2011;17(6):440-445.
To explore current practices and opinions regarding hospital management of Parkinson disease (PD) patients in specialized PD Centers.
Fifty-one out of 54 National Parkinson Foundation (NPF) Centers worldwide completed an online survey regarding hospitalization of PD patients.
Many Centers were concerned about the quality of PD-specific care provided to their patients when hospitalized. Primary concerns were adherence to the outpatient medication schedule and poor understanding by hospital staff of medications that worsen PD. Few Centers had a policy with their primary hospital that notified them when their patients were admitted. Rather, notification of hospitalization came often from the patient or a family member. Several Centers (29%) reported not finding out about a hospitalization until a routine clinic visit after discharge. Quick access to outpatient PD care following discharge was a problem in many Centers. Elective surgery, fall/fracture, infection, and mental status changes, were identified as common reasons for hospitalization.
There is a perceived need for PD specialists to be involved during hospitalization of their patients. Improvement in communication between hospitals and PD Centers is necessary so that hospital clinicians can take advantage of PD specialists’ expertise. Education of hospital staff and clinicians regarding management of PD, complications of PD, and medications to avoid in PD is critical. Most importantly, outpatient access to PD specialists needs to be improved, which may prevent unnecessary hospitalizations in these patients.
PMCID: PMC3895941  PMID: 21458353
Parkinson’s disease; Hospitalization; Complications; Deep brain stimulation; International care
5.  Cerebrospinal fluid–based kinetic biomarkers of axonal transport in monitoring neurodegeneration 
The Journal of Clinical Investigation  2012;122(9):3159-3169.
Progress in neurodegenerative disease research is hampered by the lack of biomarkers of neuronal dysfunction. We here identified a class of cerebrospinal fluid–based (CSF-based) kinetic biomarkers that reflect altered neuronal transport of protein cargo, a common feature of neurodegeneration. After a pulse administration of heavy water (2H2O), distinct, newly synthesized 2H-labeled neuronal proteins were transported to nerve terminals and secreted, and then appeared in CSF. In 3 mouse models of neurodegeneration, distinct 2H-cargo proteins displayed delayed appearance and disappearance kinetics in the CSF, suggestive of aberrant transport kinetics. Microtubule-modulating pharmacotherapy normalized CSF-based kinetics of affected 2H-cargo proteins and ameliorated neurodegenerative symptoms in mice. After 2H2O labeling, similar neuronal transport deficits were observed in CSF of patients with Parkinson’s disease (PD) compared with non-PD control subjects, which indicates that these biomarkers are translatable and relevant to human disease. Measurement of transport kinetics may provide a sensitive method to monitor progression of neurodegeneration and treatment effects.
PMCID: PMC3428100  PMID: 22922254
6.  Cognitive and Neuropsychiatric Profile of the Synucleinopathies: Parkinson's Disease, Dementia with Lewy Bodies and Multiple System Atrophy 
Parkinson's Disease (PD), multiple system atrophy (MSA) and dementia with Lewy Bodies (DLB) share α-synuclein immunoreactivity 1. These “synucleinopathies” have overlapping signs and symptoms, but less is known about similarities and differences in their cognitive and neuropsychiatric profiles. We compared the cognitive and neuropsychiatric profiles of individuals with PD, MSA and DLB. Overall, the DLB group showed the most cognitive impairment, the MSA group demonstrated milder impairment and the PD group was the least cognitively impaired. The DLB and MSA groups showed worse executive function and visuospatial skills than PD, while DLB showed impaired memory relative to both PD and MSA. On the neuropsychiatric screening, all groups endorsed depression and anxiety; the DLB group alone endorsed delusions and disinhibition. Consistent with their greater level of cognitive and neuropsychiatric impairment, the DLB group showed the greatest amount of functional impairment on a measure of instrumental ADLs (FAQ). We found that MSA subjects had cognitive difficulties that fell between the mild deficits of the PD group and the more severe deficits of the DLB group. PD, MSA and DLB groups have similar neuropsychiatric profiles of increased depression and anxiety. Similar underlying α-synuclein pathology may contribute to these shared features.
PMCID: PMC2886667  PMID: 19935145
Parkinson's Disease; Dementia with Lewy Bodies; multiple system atrophy; dementia; alpha-synuclein

Results 1-6 (6)