Journal of Parkinson's Disease - Volume 1, issue 2

Authors: Greene, James G.

Article Type: Review Article

Abstract: Gastrointestinal (GI) symptoms are being increasingly recognized as early, common, and severe features of Parkinson's disease (PD), and they are important determinants of quality of life and disability throughout the disease course. In addition, the concept that GI symptoms could represent “pre-motor” PD has been hotly debated and has recently become a driving force for investigations into the pathophysiology and neuropathology of PD. Clinical data has been supported by many pathological studies demonstrating α-synuclein neuritic pathology and neuronal loss in central and peripheral areas relevant to GI function. As understanding has matured concerning the impact of GI dysmotility on patients …and its potential relationship to incipient PD, behavioral and neuropathological examination of the GI tract has become a critical aspect of evaluation and validation of PD animal models. This review will briefly summarize GI symptoms and neuropathology in PD important to model in animals, behavioral and neuropathological examination of the GI tract in animals, and the current state of modeling parkinsonian GI dysfunction in animal model systems. Show more

Keywords: Parkinson's, gastrointestinal, enteric, constipation, gut, gastric emptying, animal models, MPTP, rotenone, synuclein

DOI: 10.3233/JPD-2011-11033

Citation: Journal of Parkinson's Disease, vol. 1, no. 2, pp. 137-149, 2011

Authors: Lelos, M.J. | Dunnett, S.B.

Article Type: Review Article

Abstract: Due to the relative success of therapeutic interventions aimed at treating the overt motor symptoms evident in Parkinson's disease (PD), a greater appreciation of the non-motor aspects of the disease has emerged in recent time. Indeed, evidence suggests that impairments in emotional processing, behavioural control and cognitive function may emerge early in the onset of the disease. Decades of experimental research have seen the development of diverse animal models, all of which have aimed to mimic the characteristic features of the disease process including the dopaminergic neural cell loss, the molecular neuropathology and the concomitant behavioural impairments. The following review …provides an overview of the use of animal, particularly rodent, models in the quest to obtain a greater understanding of the role of corticostriatal dopamine in cognitive and neuropsychiatric functions. Given the limitations of using the available rodent models of PD, including altered motor and motivational function, it has become necessary to employ a range of techniques to eke out the precise function of this neurotransmitter in corticostriatal function. Combinations of lesion and pharmacological studies have allowed the assessment of dopamine depletion and precise receptor populations in the learning or expression of a range of executive functions, which has gained us considerable insight into the relationship between the neuropathology that occurs in PD and the resulting impairments in cognitive and neuropsychiatric function. Show more

Keywords: Parkinson's disease, animal model, cognition, neuropsychiatric symptoms, executive control, 6-hydroxydopamine, rat, operant tests

DOI: 10.3233/JPD-2011-11036

Citation: Journal of Parkinson's Disease, vol. 1, no. 2, pp. 151-165, 2011

Authors: Miwa, Hideto | Kondo, Tomoyoshi

Article Type: Short Communication

Abstract: The loss of the ability to cycle after disease onset, the so-called “bicycle sign”, has been proposed as a new red flag for atypical parkinsonism. However, actual environments or situations for bicycling differ from one country to another, raising the question of whether “bicycle sign” could be universally applicable. The present study suggested that “bicycle sign” could contribute to earlier and better differential diagnosis of parkinsonism in a hilly country like Japan.

Keywords: Parkinson's disease (PD), bicycle, parkinsonism, multiple system atrophy, progressive supranuclear palsy

DOI: 10.3233/JPD-2011-11039

Citation: Journal of Parkinson's Disease, vol. 1, no. 2, pp. 167-168, 2011

Authors: Cersosimo, Maria G. | Raina, Gabriela B. | Calandra, Cristian R. | Pellene, Alejandro | Gutiérrez, Cristiam | Micheli, Federico E. | Benarroch, Eduardo E.

Article Type: Research Article

Abstract: There is involvement of salivary glands by α-synuclein pathology in PD. However, the prevalence of dry mouth has not been systematically assessed in these patients. We studied 97 PD patients and 86 controls using a structured questionnaire. Dry mouth was reported by 60.8% of PD patients and 27.9% of controls (p < 0.0001). Dry mouth and drooling coexisted in 30% of cases. Only 12% of patients had reported dry mouth to their physicians. Dry mouth is a frequent but underreported symptom and may be an early manifestation of autonomic involvement in PD.

Keywords: Parkinson's disease, hyposialorrhea, xerostomia, dry mouth, drooling

DOI: 10.3233/JPD-2011-11021

Citation: Journal of Parkinson's Disease, vol. 1, no. 2, pp. 169-173, 2011

Authors: Mak, Sally K. | Tewari, Deepika | Tetrud, James W. | Langston, J. William | Schüle, Birgitt

Article Type: Research Article

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. Show more

Keywords: SNCA triplication, Parkinson's disease, mitochondrial dysfunction, fibroblasts

DOI: 10.3233/JPD-2011-11025

Citation: Journal of Parkinson's Disease, vol. 1, no. 2, pp. 175-183, 2011

Authors: Hagell, Peter | Westergren, Albert

Article Type: Research Article

Abstract: The 12-item Short-Form Health Survey (SF-12) is an abbreviated version of the SF-36, one of the most widely used patient-reported health outcome rating scales. Similar to the SF-36, it yields summary scores of physical and mental health (PCS and MCS, respectively). However, SF-36 derived PCS and MCS scores have not been found valid in neurological disorders such as Parkinson's disease (PD). Here we used modern psychometric methodology (Rasch analysis) to test the SF-12 in PD, and explored the appropriateness of a total SF-12 score representing overall health. SF-12 data from 150 non-demented people with PD (56% men; mean age/PD-duration, 70/5 …years) were analyzed regarding Rasch model fit for the PCS, MCS, as well as for the full SF-12. Data showed some signs of misfit to the Rasch model for all three scales (overall item-trait interaction, P ≥ 0.003; reliability, ≥ 0.85). For example, all scales exhibited signs of dependency between item responses, and the PCS measured with relatively low precision. Model fit (but not measurement precision) was improved following deletion of one PCS and one MCS item (overall item-trait interaction, P ≥ 0.387; reliability, ≥ 0.82). These observations suggest that the SF-12 can be used as a coarse health survey tool in PD and that a total SF-12 may be useful as a measure of overall health. However, its appropriateness as an outcome measure can be questioned and it is somewhat unclear exactly what the derived scores represent. As such, the SF-12 should probably be considered an assessment tool (or index) rather than a measurement instrument. Show more

Keywords: Health status, outcome assessment, Parkinson disease, psychometrics

DOI: 10.3233/JPD-2011-11026

Citation: Journal of Parkinson's Disease, vol. 1, no. 2, pp. 185-196, 2011

Authors: Martinez-Martin, Pablo | Reddy, Prashanth | Antonini, Angelo | Henriksen, Tove | Katzenschlager, Regina | Odin, Per | Todorova, Antonia | Naidu, Yogini | Tluk, Susanne | Chandiramani, Chandni | Martin, Anne | Chaudhuri, Kallol Ray

Article Type: Research Article

Abstract: Background: Apomorphine infusion therapy remains under-used and there are no comparative studies of motor and non-motor effects of apomorphine infusion. Methods: In this paper we report preliminary results from an ongoing clinical observational “real life” surveillance-based study focused on effects of this therapy on non-motor symptoms and health-related quality of life in a group of patients on apomorphine. Results: Apomorphine infusion led to highly significant improvements in UPDRS 3 (p = 0.0003), UPDRS 4 (p = 0.0003), PDQ-8 (Parkinson's disease questionnaire, p = 0.001) and NMSS total (non motor symptoms scale, p = 0.0003). Furthermore, apomorphine was tolerated in patients …with visual hallucinations, illusions and paranoid ideations while significant improvement in specific non-motor symptoms such as hyperhidrosis, nocturia, urgency of micturition, and fatigue was recorded. Levodopa equivalent dose decreased significantly (1077.81 ± 446.26 to 458.75 ± 282.29, p < 0.0001) and a large effect size of intervention was noted. In an untreated group no such improvement was noted. The number needed to treat (NNT) for improvement >1 SEM in the Apo group was calculated and was lower than 2 for >1 SEM improvement of UPDRS 3, NMSS, and PDQ-8 total scores. Conclusions: This pilot observational study suggests that non-motor effects are evident with apomorphine therapy and patients suitable for apomorphine deteriorate in the absence of therapy. Show more

DOI: 10.3233/JPD-2011-11037

Citation: Journal of Parkinson's Disease, vol. 1, no. 2, pp. 197-203, 2011

Authors: Levin, Johannes | Högen, Tobias | Hillmer, Andreas S. | Bader, Benedikt | Schmidt, Felix | Kamp, Frits | Kretzschmar, Hans A. | Bötzel, Kai | Giese, Armin

Article Type: Research Article

Abstract: Background: Synucleinopathies such as Parkinson's disease are characterized by the deposition of aggregated α-synuclein in affected brain areas. As genes involved in mitochondrial function, mitochondrial toxins, and age-related mitochondrial impairment have been implicated in Parkinson's disease pathogenesis, an increase in reactive oxygen species resulting from mitochondrial dysfunction has been speculated to induce α-synuclein aggregation. In vitro, pore-forming, SDS-resistant α-synuclein oligomers are formed in presence of ferric iron and may represent an important toxic particle species. Methodology/Principal findings: We investigated the interplay of reactive oxygen species, antioxidants and iron oxidation state in regard to α-synuclein aggregation using confocal single particle fluorescence …spectroscopy, Phenanthroline spectrometry and thiobarbituric acid reactive substances assay. We found that the formation of α-synuclein oligomers in presence of Fe3+ is due to a direct interaction. In contrast, oxidizing agents and hydroxyl radicals generated in the Fenton reaction did not directly affect α-synuclein oligomerization. However, reactive oxygen species could enhance aggregation via oxidation of ferrous to ferric iron when iron ions were present. Conclusions/Significance: Our data thus indicate that oxidative stress affects α-synuclein aggregation via oxidation of iron to the ferric state. This provides a new perspective on the role of mitochondrial toxins and mitochondrial dysfunction in the pathogenesis of Parkinson's disease. Show more

Keywords: Parkinson's disease, α-synuclein, iron, oxidative stress, protein aggregation, pesticides

DOI: 10.3233/JPD-2011-11040

Citation: Journal of Parkinson's Disease, vol. 1, no. 2, pp. 205-216, 2011