Parkinsonism & Related Disorders

Editorial Board

2010-03-01

Identification and management of deep brain stimulation intra- and postoperative urgencies and emergencies

2010-03-01

Abstract: Deep brain stimulation (DBS) has been increasingly utilized for the therapeutic treatment of movement disorders, and with the advent of this therapy more postoperative urgencies and emergencies have emerged. In this paper, we will review, identify, and suggest management strategies for both intra- and postoperative urgencies and emergencies. We have separated the scenarios into 1 – surgery/procedure related, 2 – hardware related, 3 – stimulation-induced difficulties, and 4 – others. We have included ten illustrative (and actual) case vignettes to augment the discussion of each issue.

Conjugal Parkinsonism and Parkinson disease: A case series with environmental risk factor analysis

Allison W. Willis, Callen Sterling, Brad A. Racette — 2010-03-01

Abstract: PD occurring in married couples, “conjugal PD” represents a unique opportunity to study environmental risk factors for PD due to the shared environment. This retrospective study of non-related married individuals who both presented to the Washington University Movement Disorders Center between 1994 and 2005 investigated the clinical presentation, therapy response, and disease course in conjugal PD subjects. In addition, an occupational, residential, and environmental survey was administered to elucidate potential shared environmental risk factors.Eighteen married subjects had a clinical picture suggestive of idiopathic Parkinson disease. Average age of motor symptom onset was 66.1 (±6.22) years in women, 63.4 (±7.87) years in men. Subjects cohabitated an average of 39.9 years prior to motor symptom onset in the first affected spouse and an average of nine years elapsed prior to symptom onset in their partner. Disease course in conjugal pairs varied substantially.Seventeen out of eighteen subjects reported at least one environmental exposure of interest. Concordant exposures were residential, non-occupational pesticide and heavy metal exposure, each reported by 77.8% (7/9) of couples. Multiple exposures were reported by 88.9% (16/18) of subjects, most often residential agricultural chemical and heavy metal in combination. This case series of conjugal PD suggests that combined residential exposures may be important in the pathogenesis of idiopathic PD. Larger conjugal PD studies may permit stratification of concordant environmental exposures to determine dose responsiveness and relative contributions to PD risk.

Evaluation of PINK1 variants in Indian Parkinson's disease patients

2010-03-01

Abstract: Mutations in PINK1 have been identified in familial and sporadic cases of early onset Parkinson's disease (PD). To determine the contribution of PINK1 variants in Indian PD patients, the gene was screened in 250 patients and 205 ethnically matched controls by polymerase chain reaction, single-stranded conformation polymorphism and DNA sequencing. Two potentially pathogenic variants (Arg246Gln & Arg276Gln) were detected in the heterozygous state in 5 patients; none of the patients carried homozygous or compound heterozygous mutations. In addition, 13 other variants were identified, including a known polymorphism (Ala340Thr), a few synonymous or intronic changes, none of which are likely to be pathogenic. Unlike the Chinese population, the Ala340Thr variant did not show any association with PD in Indian population. Six single nucleotide polymorphisms (SNPs) selected from dbSNP were genotyped in 531 normal, healthy individuals representing different ethnic groups of India. Most of the SNP markers were observed to be highly heterozygous among Indians, which could be used for segregation analysis of PINK1 alleles in familial PD cases.

Sexual and relationship dysfunction in people with Parkinson's disease

Annette Hand, William K. Gray, Barbara J. Chandler, Richard W. Walker — 2010-03-01

Abstract: Objectives: To quantify the extent of self-reported sexual and relationship problems in people with Parkinson's disease (PD).Methods: A cross-sectional correlation design was used. All people with idiopathic PD, according to the UK Brain Bank criteria, who were known to the Northumbria Healthcare NHS Trust PD service, were asked to participate. Those who consented were assessed by a research nurse during a six month period using a series of rating scales, including the Unified Parkinson's Disease Rating Scale (UPDRS), the PD Questionnaire-39, the Mini Mental State Examination (MMSE), the Szasz sexual functioning scale and, for those in long-term relationships, the Golombok Rust Inventory of Marital State.Results: Concern over sexual function was reported in 22 (25%) of the 88 participants in the study. Males (p = 0.001) and younger people with PD (p = 0.001) were significantly more likely to report problems with sexual function. Gender (p = 0.007) and UPDRS score (p = 0.045) were significant independent predictors of relationship problems. Males with PD and those with increasing functional problems (UPDRS score) were more likely to report problems in their relationship. Disease duration and levels of anxiety and depression (Hospital Anxiety and Depression scale) were not associated with sexual or relationship problems.Conclusions: Sexual and relationship dysfunction was a problem for many people in this study, but these problems were unlikely to be volunteered unless specifically enquired about. Problems were apparent across all age groups and genders.

Mild cognitive impairment in Parkinson's disease: Subtypes and motor characteristics

2010-03-01

Abstract: The aims of this project were to determine the risk factors for and clinical characteristics of mild cognitive impairment (MCI) in Parkinson's disease (PD). We performed a retrospective record review of 72 non-demented PD patients (age: 57.79 ± 10.57, duration of PD: 7.32 ± 4.97) who completed a standardized neurological assessment, including a full neuropsychological battery, as part of their diagnostic work-up. Of these participants, 47.2% were cognitively normal and 52.8% met criteria for MCI. The majority of MCI patients had single domain MCI (23/38), the affected domains being memory (n = 9), executive function (n = 6), visuospatial skills (n = 6), and language (n = 2). The MCI group had longer duration of disease and higher postural instability and gait disorder subscale scores than the cognitively normal group. This report provides further support for use of the concept of MCI in PD research. There may be certain disease characteristics that could alert practitioners to the emergence of cognitive changes in patients. Future studies should focus on additional risk factors for MCI subtypes and their possible progression to frank dementia.

Refinement and validation of the Parental Illness Impact Scale

David Morley, Caroline Selai, Anette Schrag, Alan J. Thompson, Marjan Jahanshahi — 2010-03-01

Abstract: Objective: To refine and validate the Parental Illness Impact Scale (PIIS), a questionnaire designed specifically to measure the quality of life of adolescent and adult children of neurologically affected parents.Methods: Key informant interviews and a literature review were conducted to ensure all relevant themes were incorporated in the revised PIIS (PIIS-R). Pre-testing was achieved through a 17 member expert panel and cognitive interviews with eight adolescent and adult children. The revised instrument was administered to 169 adolescent and adult children of people with Parkinson's disease, multiple sclerosis and stroke and subjected to psychometric analysis.Results: Principal components analysis resulted in eight subscales accounting for 60.6% of explained variance. The PIIS-R showed good concurrent and discriminant validity through correlations with established measures of quality of life and psychosocial well-being. Internal consistency was high (Cronbach's α .92), and test-retest reliability values for subscales (r = .59–.74) and total score (r = .79) were moderate to high.Conclusions: The PIIS-R is a scientifically robust measurement tool for assessing the impact of parental illness, and currently shows strong psychometric properties. Longitudinal data will be required to assess predictive validity and sensitivity to change. The instrument is available to other investigators, who are encouraged to further evaluate its scientific properties.

Cancer risk in association with Parkinson disease: A population-based study

2010-03-01

Abstract: Purpose: Data from large population-based studies on the association between Parkinson disease (PD) and the risk of developing cancer are scarce. We compared the risk of developing incident cancer between patients with or without PD.Methods: We conducted a population-based follow-up study and a nested case-control analysis using data from the UK-based General Practice Research Database. We included PD patients aged ≥40 years with a first PD diagnosis between 1994 and 2005, and a matched comparison group free of PD. We assessed cancer incidence rates and relative risk estimates (odds ratios [ORs] with 95% confidence intervals [CI]).Results: The risk of developing cancer overall was lower in PD patients as compared to patients without PD (crude incidence rate ratio 0.77, 95% CI 0.64–0.92). In the nested case-control analysis (adj. OR for all cancers 0.72, 95% CI 0.59–0.87) the risk reduction was strongest for smoking-related cancers (adj. OR 0.47, 95% CI 0.31–0.72). The adjusted OR for hematological malignancies was 0.32 (95% CI 0.14–0.74). Due to small numbers, ORs for other cancer entities did not reach statistical significance.Conclusions: With the exception of melanoma, PD patients were less likely to develop cancer than individuals without PD in this large observational study.

Planned stopping in people with Parkinson

D. Cameron, A. Murphy, M.E. Morris, S. Raghav, R. Iansek — 2010-03-01

Abstract: The aim of this study was to quantify gait termination in people with Parkinson (PwP) as the basis for understanding the underlying pathophysiology of stopping difficulties. Fourteen PwP and 14 age- and gender-matched comparisons completed five trials each of four walking tasks: preferred walk, preferred walk with secondary motor task, coming to a planned stop, and planned stop with a secondary motor task. Spatio-temporal data of walks were compared to steady state walking in stopping trials. Results showed that PwP walked with shorter step length, slower speed, yet similar cadence to comparisons. Both groups decreased step length and step speed when performing a secondary task. Neither group showed changes of gait characteristics in steady state walking prior to stopping. For stopping trials, the number of steps, time, and distance taken to stop were compared for PwP and controls. In planned stops PwP used more steps and took a longer time to stop, but both groups stopped within a similar distance. A secondary motor task did not alter stopping distance or number of steps to stop, but stopping time increased in the comparisons. The results indicate that central control mechanisms regulating planned stopping appear to be intact in people with mild to moderate Parkinson.

Sensitivity and specificity of the finger tapping task for the detection of psychogenic movement disorders

Susan Criswell, Callen Sterling, Laura Swisher, Brad Evanoff, Brad A. Racette — 2010-03-01

Abstract: Psychogenic movement disorders (PMD) represent a diagnostically challenging group of patients in movement disorders. Finger tapping tests (FTT) have been used in neuropsychiatric evaluations to identify psychogenic conditions, but their use in movement disorders has been limited to the quantification of upper extremity disability in idiopathic Parkinson disease (IPD). We evaluated the ability of the FTT to objectively identify PMD by screening 195 individuals from a movement disorder clinic with IPD, dystonia, essential tremor, or PMD and compared them to 130 normal adults. All subjects performed six-30 s trials using alternate hands. We compared mean FTT score and the coefficient of variation between diagnostic groups. FTT scores in IPD were inversely correlated with Hoehn and Yahr stage (p < 0.001) and the United Parkinson Disease Rating Scale III (motor) subscale (p < 0.001). FTT scores were significantly lower in PMD (mean = 41.72) when compared to the other diagnostic groups after controlling for age. The coefficient of variation was not significantly different between diagnostic groups. ROC analysis identified a cutoff FTT ratio of 0.670 or less was 89.1% specific and 76.9% sensitive for the diagnosis of PMD. We conclude the FTT can provide supportive evidence for the diagnosis of PMD.

Association between the dose of dopaminergic medication and the behavioral disturbances in Parkinson disease

2010-03-01

Abstract: Objectives: To survey the point prevalence of impulse control and repetitive behavior disorders (ICRBs) in patients with Parkinson disease (PD) and to determine the relationship between PD medication dose and the risk of ICRBs.Methods: A multicenter cross-sectional survey was applied to consecutive patients with PD over a 3-month period. The presence of ICRBs was screened using a modified version of the Minnesota Impulsive Disorders Interview that comprised five ICRB modules: compulsive buying, gambling, sexual behavior, eating, and punding. Data regarding the patients' clinical features and concurrent anti-PD drugs were also collected during the interview. Adjusted odds ratios (ORs) of the daily doses of dopamine agonist and l-dopa for the development of an ICRB were calculated after adjustment for clinical variables.Results: Among the 1167 patients recruited, 118 (10.1%) exhibited ICRBs. Punding was the most common ICRB (4.2%), followed by compulsive eating (3.4%), sexual behaviors (2.8%), buying (2.5%), and gambling (1.3%). Two or more ICRBs were present concomitantly in 34 of these 118 patients (28.8%). There were dose–response relationships between the dopamine agonist dose and the ORs for compulsive buying, gambling and sexual behaviors. On the other hand, the OR for punding was positively correlated with the dose of l-dopa. The OR for compulsive eating was not associated with the dose of dopamine agonist or l-dopa.Conclusions: The dose of dopaminergic medication is significantly associated with the development of ICRB, except compulsive eating, in PD.

Symmetric corticobasal degeneration (S-CBD)

2010-03-01

Abstract: Background: Corticobasal degeneration (CBD) is a neurodegenerative disease characterized pathologically by neuronal loss, gliosis and tau deposition in neocortex, basal ganglia and brainstem. Typical clinical presentation is known as corticobasal syndrome (CBS) and involves the core features of progressive asymmetric rigidity and apraxia, accompanied by other signs of cortical and extrapyramidal dysfunction. Asymmetry is also emphasized on neuroimaging.Objective: To describe a series of cases of CBD with symmetric clinical features and to compare clinical and imaging features of these symmetric CBD cases (S-CBD) to typical cases of CBS with CBD pathology.Methods: All cases of pathologically confirmed CBD from the Mayo Clinic Rochester database were identified. Clinical records were reviewed and quantitative volumetric analysis of symmetric atrophy on head MRI using atlas based parcellation was performed. Subjects were classified as S-CBD if no differences had been observed between right- and left-sided cortical or extrapyramidal signs or symptoms. S-CBD cases were compared to 10 randomly selected typical CBS cases.Results: Five cases (2 female) met criteria for S-CBD. None had limb dystonia, myoclonus, apraxia or alien limb phenomena. S-CBD cases had significantly less asymmetric atrophy when compared with CBS cases (p=0.009); they were also younger at onset (median 61 versus 66 years, p<0.05) and death (67 versus 73 years, p<0.05). Family history was present in 40% of S-CBD cases.Conclusions: CBD can have a symmetric presentation, clinically and radiologically, in which typical features of CBS, such as limb apraxia, myoclonus, dystonia and alien limb phenomenon, may be absent.

Working capacity and cervical dystonia

Kirsti K. Martikainen, Tiina H. Luukkaala, Reijo J. Marttila — 2010-03-01

Abstract: The objective of this questionnaire study was to assess the effect of cervical dystonia on patients' working capacity. Of the 303 working-aged members of the Finnish Dystonia Association (N = 433) who participated in the study 247 (82%) had cervical dystonia. Their median age was 50 years, the median duration of CD symptoms was 12.3 years. Most (78%) subjects were on botulinum toxin treatment. Ninety-seven (39%) had retired because of CD at a median age of 48 years; 96 (39%) of the subjects were working: 87 full-time and 9 part-time. The remaining participants were on sick leave, unemployed, studying or retired of other reasons. Retirement occurred more than ten years earlier compared with the general Finnish population. All possibilities to help CD patients to continue longer in work should be considered early.

Eighteen month study of continuous intraduodenal levodopa infusion in patients with advanced Parkinson's disease: Impact on control of fluctuations and quality of life

2010-03-01

Abstract: Symptom control, daily “on” time, and quality of life (QoL) of nine patients with Advanced Parkinson's Disease was assessed following 18-months treatment with Continuous Intraduodenal Levodopa Infusion (CIDLI). Patients had severe motor fluctuations and dyskinesias and had previously received treatment with oral levodopa and dopamine agonists. There were significant improvements in patients' symptoms on the Unified Parkinson's Disease Rating Scale, and QoL (Parkinson's Disease QoL Questionnaire; Schwab & England Capacity for Daily Living Scale; p < 0.05). Mean (±SD) daily “on” time increased from 6.1 ± 1.9 to 12.0 ± 3.4 h (p < 0.05). Improved QoL in APD was associated with CIDLI-related improvements in symptom control and increase in daily “on” time.

Genetic screening for mutations in the Nrdp1 gene in Parkinson disease patients in a Chinese population

2010-03-01

Abstract: Strong evidence has shown that a defect in the Parkin gene is known to be a common, genetic cause of Parkinson disease (PD). The E3 ubiquitin ligase Nrdp1 is shown to interact with the N terminal of Parkin (the first 76 amino acids) and catalyze degradation of Parkin via the ubiquitin–proteasome pathway, suggesting that Nrdp1 may be involved in the development of PD via the regulation of Parkin, We believe we are the first to have screened PD patients for mutations in the Nrdp1 gene to determine the association between these variants and PD. By direct sequencing, we analysed the entire coding regions and 5′ UTR of Nrdp1 in 209 Chinese PD patients and 302 unrelated healthy individuals. No variant was detected in the coding regions (exons 3–7); only 2 variants (c.−206 T > A and c.−208–8 A > G) were identified in the 5′ UTR (exon 2) and intron 1. Furthermore, a study of the allelic and genotypic association between patients and controls showed no significant association between the c.−206 T > A polymorphism and PD; c.−208–8 A > G was identified in one PD patient and not in controls. Our data do not support the hypothesis of a major role for the Nrdp1 gene in PD development in the Chinese population.

The effect of levodopa treatment on cerebral hemodynamics in patients with Parkinson's disease: Serial transcranial Doppler studies

Seok Woo Yong, Kyung Yul Lee, Phil Hyu Lee — 2010-03-01

Abstract: Levodopa treatment in patients with Parkinson's disease (PD) is known to cause elevation in serum homocysteine levels. We investigated whether this increase in homocysteine level influences cerebral vascular flow velocity and resistance using transcranial Doppler (TCD). This study included 17 patients with de novo PD. Homocysteine levels and TCD parameters at middle cerebral artery were investigated before and after 3 months of levodopa treatment. Correlation analyses were done between changes in homocysteine levels and TCD parameters. After 3 months of levodopa treatment, homocysteine level increased significantly from 13.3mg/dL to 17.0 mg/dL (p < 0.001), but there were no meaningful changes in mean velocity (MV) and pulsatility index (PI). Correlation analysis revealed that the changes in homocysteine level had negative correlation with MV (r = −0.53, p = 0.027) and positive correlation with PI (r = 0.55, p = 0.028). Our study infer that although short-term treatment of levodopa itself does not cause overall alteration of cerebral blood flow velocities and resistances, patients who has greater degree of increased homocysteine level may still be at a risk of developing cerebral vascular stiffness.

α-Synuclein multiplication analysis in Italian familial Parkinson disease

2010-03-01

Abstract: The α-synuclein gene (SNCA) multiplication causes autosomal dominant Parkinson Disease (PD): triplication is associated with early-onset rapidly progressing parkinsonism with a strong likelihood of developing dementia, while duplication is associated with a less severe phenotype similar to idiopathic PD.We tested for SNCA multiplication 144 unrelated PD patients with a dominant family history. We identified one patient with SNCA duplication (0.7%).The SNCA-duplicated patient was a woman of 45 years of age with PD onset at 41 years of age. She experienced a rapidly progressive disease with early motor complications (on/off fluctuations and dyskinesias). Medical records confirmed that the proband's mother developed PD at 47 years of age and died at 63 with dementia. She experienced rapid progression in both motor and cognitive symptoms: development of dementia at 54 years of age, 7 years after onset.Although SNCA duplication is an unusual cause of familial PD testing for it is worthwhile. The clinical presentation of duplicated cases may be more aggressive than usual.

Conjugal parkinsonism: Multiple system atrophy and Parkinson's disease

Hideto Miwa, Tomoyoshi Kondo — 2010-03-01

We read with a great interest a recent article on conjugal parkinsonism and Parkinson's disease (PD) . The authors accumulated a total of nine couples with conjugal parkinsonism, and analyzed their clinical pictures as well as environmental risk factors. They noted that combined residential exposure to agricultural chemicals and heavy metals was the most frequent risk factor. Analysis of conjugal PD could provide a good opportunity to study environmental risk factors for PD.

Digitized spiral analysis is a promising early motor marker for Parkinson Disease

2010-03-01

Clinical trials of Parkinson disease (PD) are shaped by the sensitivity of the metrics used to measure dysfunction. While sequential Unified Parkinson Disease Rating Scale (UPDRS) motor scores reflect disease progression , objective quantitative motor assessments may be more sensitive in detecting early disease and may supplement the UPDRS. Spiral analysis is a graphonometric method of assessing upper limb kinematics by digitizing and analyzing Archimedean spirals drawn on a digitized graphics tablet that correlates with the motor UPDRS score . It has the advantage of being non-invasive and relatively easy to perform. To test if spiral analysis could detect changes not clinically measurable by UPDRS, we assessed whether spiral analysis could identify abnormalities on the unaffected side in a unique population of early and clinically unilateral PD (i.e. normal motor UPDRS scores on one side of the body).

ATP13A2 G2236A variant is rare in patients with early-onset Parkinson's disease and familial Parkinson's disease from mainland China

2010-03-01

The ATP13A2 gene, also named PARK9, was initially described as the causative gene of Kufor Rakeb disease (KRD) in a KRD family. The genetic locus was mapped to the chromosome 1p36 region, within a cluster of early-onset Parkinson's disease (PD) loci . The gene covers 26kb and 29 coding exons and the open reading frame (ORF) consists of 3,543 nucleotides encoding a large, 1,180 amino acids transmembrane protein which belongs to the Group 5 P-type ATPase superfamily, with its characteristic ten-transmembrane domain topology .