Journal of Parkinson's Disease - Volume 4, issue 3

Authors: Palfreman, Jon

Article Type: Other

DOI: 10.3233/JPD-149003

Citation: Journal of Parkinson's Disease, vol. 4, no. 3, pp. 313-316, 2014

Authors: Piro, Anna | Tagarelli, Antonio | Nicoletti, Giuseppe | Fletcher, Robert | Quattrone, Aldo

Article Type: Research Article

DOI: 10.3233/JPD-140359

Citation: Journal of Parkinson's Disease, vol. 4, no. 3, pp. 317-319, 2014

Authors: Egevad, Gustav | Petkova, Valentina Yankova | Vilholm, Ole Jakob

Article Type: Review Article

Abstract: Sialorrhea may present as a troublesome symptom in patients suffering from Parkinson's disease. Current options for treatment include anticholinergic drugs, irradiation, surgery, oral-motor and behavioural therapies, and injection of botulinum neurotoxin (BoNT) in the salivary glands. The aim of this study is to evaluate the safety and administration of BoNT as a treatment for sialorrhea in patients with Parkinson's disease (PD) based on a review of the studies conducted so far in this field. A PubMed search was conducted using the major keywords sialorrhea, botulinum neurotoxin, botulinum toxin and Parkinson's disease. The literature search identified 12 articles, which were selected …for further analysis. Few adverse effects were described in the studies included in this present review. Various treatment strategies, including different medication dosages, were applied in the studies. BoNT treatment is safe for sialorrhea in patients with PD. Positive effect is well documented, and there have been relatively few reported adverse effects, which have been mild and transient. Based on this review, a treatment algorithm is proposed. Ultrasound guidance may not be necessary when injecting the parotid gland but may improve the effect and safety of administration, especially when injecting the submandibular glands. Show more

Keywords: Parkinson's disease, sialorrhea, drooling, botulinum neurotoxin, treatment

DOI: 10.3233/JPD-140379

Citation: Journal of Parkinson's Disease, vol. 4, no. 3, pp. 321-326, 2014

Authors: Krøigård, Thomas | Christensen, Jane | Wermuth, Lene | Ritz, Beate | Lassen, Christina Funch

Article Type: Short Communication

Abstract: Previous studies have suggested that dopamine agonists have an antidepressant effect in Parkinson's disease (PD) patients. We examined whether fewer PD patients used antidepressant medication, when they were first treated with a dopamine agonist compared to other PD medications. PD patients diagnosed in Denmark were identified, and the diagnosis was confirmed by a review of the medical record. Antidepressant medication was assessed using the Danish National Prescription Registry. We used Cox proportional hazards regression to model the association between PD medications and time to antidepressant prescription. The type of PD medication first prescribed did not affect the subsequent use of …antidepressants. Show more

Keywords: Antidepressant medication, depression, dopamine agonists, levodopa, MAO-B inhibitors, Parkinson's disease

DOI: 10.3233/JPD-140386

Citation: Journal of Parkinson's Disease, vol. 4, no. 3, pp. 327-330, 2014

Authors: Lawson, Rachael A. | Yarnall, Alison J. | Duncan, Gordon W. | Khoo, Tien K. | Breen, David P. | Barker, Roger A. | Collerton, Daniel | Taylor, John-Paul | Burn, David J.

Article Type: Short Communication

Abstract: We evaluated the association between mild cognitive impairment (MCI) subtypes and quality of life (QoL) in 219 newly diagnosed Parkinson’s disease (PD) patients without dementia. Participants completed neuropsychological tests of attention, executive function, visuospatial function, memory, and language, and reported QoL using the Parkinson’s Disease Questionnaire. Impairments were most common in executive function, memory and attention. MCI subtypes were classified according to Movement Disorder Society Task Force criteria. More severe cognitive impairment was associated with poorer quality of life (p = 0.01), but subtype of impairment was not (p > 0.10), suggesting that the nature of cognitive impairment …is less significant than its severity. Show more

Keywords: Parkinson’s disease, quality of life, mild cognitive impairment, subtypes

DOI: 10.3233/JPD-140390

Citation: Journal of Parkinson's Disease, vol. 4, no. 3, pp. 331-336, 2014

Authors: Aviles-Olmos, Iciar | Dickson, John | Kefalopoulou, Zinovia | Djamshidian, Atbin | Kahan, Joshua | Ell, Peter | Whitton, Peter | Wyse, Richard | Isaacs, Tom | Lees, Andrew | Limousin, Patricia | Foltynie, Thomas

Article Type: Research Article

Abstract: Background: Data from an open label randomised controlled trial have suggested possible advantages on both motor and non-motor measures in patients with Parkinson’s disease following 12 months exposure to exenatide. Objective: Continued follow up of these same patients was performed to investigate whether these possible advantages persisted in the prolonged absence of this medication. Methods: All participants from an open label, randomised controlled trial of exenatide as a treatment for Parkinson’s disease, were invited for a further follow up assessment at the UCL Institute of Neurology. This visit included all 20 individuals who had previously …completed twelve months exposure to exenatide 10ug bd and the 24 individuals who had acted as randomised controls. Motor severity of PD was compared after overnight withdrawal of conventional PD medication using blinded video assessment of the MDS-UPDRS, together with several non-motor tests. This assessment was thus 24 months after their original baseline visit, i.e. 12 months after cessation of exenatide. Results: Compared to the control group of patients, patients previously exposed to exenatide had an advantage of 5.6 points (95% CI, 2.2–9.0; p = 0.002) using blinded video rating of the MDS-UPDRS part 3 motor subscale. There was also a difference of 5.3 points; (95% CI, 9.3–1.4; p = 0.006) between the 2 groups on the Mattis Dementia Rating scale. Conclusions: While these data must still not be interpreted as evidence of neuroprotection, they nevertheless provide strong encouragement for the further study of this drug as a potential disease modifying agent in Parkinson’s disease. Show more

Keywords: Parkinson’s disease, clinical trial, disease modifying treatment, UPDRS, exenatide, diabetes mellitus

DOI: 10.3233/JPD-140364

Citation: Journal of Parkinson's Disease, vol. 4, no. 3, pp. 337-344, 2014

Authors: Simuni, Tanya | Brundin, Patrik

Article Type: Research Article

Abstract: A recent study by Aviles-Olmos and colleagues suggests that 12 months of treatment with the glucagon-like peptide-1 receptor agonist exenatide improves motor and cognitive symptoms in Parkinson's disease (PD), and that the effect persists as long as 12 months after termination of the treatment. Due to the lack of a placebo control, one cannot exclude that the observed differences between patients receiving daily injections of exenatide and non-treated controls are due to a placebo effect. We discuss that large group differences in two independent functional measures remain for at least 12 months following the cessation of exenatide treatment and that …this warrants a double-blind placebo-controlled trial with exenatide in PD. Show more

DOI: 10.3233/JPD-149001

Citation: Journal of Parkinson's Disease, vol. 4, no. 3, pp. 345-347, 2014

Authors: Barnum, Christopher J. | Chen, Xi | Chung, Jaegwon | Chang, Jianjun | Williams, Martha | Grigoryan, Nelly | Tesi, Raymond J. | Tansey, Malú G.

Article Type: Research Article

Abstract: Background: Parkinson's disease (PD) is a complex multi-system age-related neurodegenerative disorder. Targeting the ongoing neuroinflammation in PD patients is one strategy postulated to slow down or halt disease progression. Proof-of-concept studies from our group demonstrated that selective inhibition of soluble Tumor Necrosis Factor (solTNF) by intranigral delivery of dominant negative TNF (DN-TNF) inhibitors reduced neuroinflammation and nigral dopamine (DA) neuron loss in endotoxin and neurotoxin rat models of nigral degeneration. Objective: As a next step toward human clinical trials, we aimed to determine the extent to which peripherally administered DN-TNF inhibitor XPro® 1595 could: i) cross the blood-brain-barrier in therapeutically …relevant concentrations, ii) attenuate neuroinflammation (microglia and astrocyte), and iii) mitigate loss of nigral DA neurons in rats receiving a unilateral 6-hydroxydopamine (6-OHDA) striatal lesion. Methods: Rats received unilateral 6-OHDA (20 μg into the right striatum). Three or 14 days after lesion, rats were dosed with XPro® 1595 (10 mg/kg in saline, subcutaneous) every third day for 35 days. Forelimb asymmetry was used to assess motor deficits after the lesion; brains were harvested 35 days after the lesion for analysis of XPro® 1595 levels, glial activation and nigral DA neuron number. Results: Peripheral subcutaneous dosing of XPro® 1595 achieved plasma levels of 1–8 microgram/mL and CSF levels of 1–6 ng/mL depending on the time the rats were killed after final XPro® 1595 injection. Irrespective of start date, XPro® 1595 significantly reduced microglia and astrocyte number in SNpc whereas loss of nigral DA neurons was attenuated when drug was started 3, but not 14 days after the 6-OHDA lesion. Conclusions: Our data suggest that systemically administered XPro® 1595 may have disease-modifying potential in PD patients where inflammation is part of their pathology. Show more

Keywords: Parkinson's disease, inflammation, tumor necrosis factor, 6-OHDA, microglia, substantia nigra, $XPro^{\reg}1595$, astrocytes

DOI: 10.3233/JPD-140410

Citation: Journal of Parkinson's Disease, vol. 4, no. 3, pp. 349-360, 2014

Authors: Nicholas, Anthony P. | Borgohain, Rupam | Chaná, Pedro | Surmann, Erwin | Thompson, Emily L. | Bauer, Lars | Whitesides, John | Elmer, Lawrence W.

Article Type: Research Article

Abstract: Background: Previous phase III studies in patients with advanced Parkinson's disease (PD) not adequately controlled on levodopa demonstrated significant reduction of ‘off’ time with rotigotine transdermal system up to 16 mg/24 h. However, the minimal effective dose has not been established. Objective: This international, randomized, double-blind, placebo-controlled study (SP921; NCT00522379) investigated rotigotine dose response up to 8 mg/24 h. Methods: Patients with advanced idiopathic PD (≥2.5 h of daily ‘off’ time on stable doses of levodopa) were randomized 1:1:1:1:1 to receive rotigotine 2, 4, 6, or 8 mg/24 h or placebo, titrated over 4 weeks and maintained for 12 weeks. …The primary efficacy variable was change from baseline to end of maintenance in absolute time spent ‘off’. Results: 409/514 (80%) randomized patients completed maintenance. Mean (±SD) baseline daily ‘off’ times (h/day) were placebo: 6.4 (±2.5), rotigotine 2–8 mg/24 h: 6.4 (±2.6). Rotigotine 8 mg/24 h was the minimal dose to significantly reduce ‘off’ time versus placebo. LS mean (±SE) absolute change in daily ‘off’ time (h/day) from baseline was −2.4 (±0.28) with rotigotine 8 mg/24 h, and −1.5 (±0.26) with placebo; absolute change in ‘off’ time in the 8 mg/24 h group compared with placebo was −0.85 h/day (95% CI −1.59, −0.11; p = 0.024). There was an apparent dose-dependent trend. Adverse events (AEs) reported at a higher incidence in the rotigotine 8 mg/24 h group versus placebo included application site reactions, nausea, dry mouth, and dyskinesia; there was no worsening of insomnia, somnolence, orthostatic hypotension, confusional state or hallucinations, even in patients ≥75 years of age. Conclusions: The minimal statistically significant effective dose of rotigotine to reduce absolute ‘off’ time was 8 mg/24 h. The AE profile was similar to previous studies. Show more

Keywords: Parkinson's disease, randomized controlled trial, dopamine receptor agonist, dose-response relationship, rotigotine

DOI: 10.3233/JPD-130320

Citation: Journal of Parkinson's Disease, vol. 4, no. 3, pp. 361-373, 2014

Authors: Wang, Zhi-Yong | Lian, Hui | Cai, Qing-Qing | Song, Hai-Yan | Zhang, Xiao-Li | Zhou, Li | Zhang, Yi-Min | Zheng, Li-Fei | Zhu, Jin-Xia

Article Type: Research Article

Abstract: Background: Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by degeneration of dopaminergic neurons in the substantia nigra (SN). Destruction of the SN can lead to gastric dyskinesis accompanied by decreased expression of choline acetyltransferase (ChAT) and increased expression of tyrosine hydroxylase (TH) in the dorsal vagus complex (DVC), which includes the dorsal motor nucleus of the vagus (DMV) and nucleus tractus solitarius (NTS). However, it is unclear if the SN and DVC are directly connected. Objective: To investigate the neural projection from the SN to the DVC in rats. Methods: Retrograde and anterograde tracing techniques combined with …double-labeling immunofluorescence technique were used. Results: Destruction of the SN significantly decreases ChAT immunoreactivity (IR) and increases TH-IR in the DVC. After injection of the retrograde tracer fluoro-gold (FG) into the DVC, FG-labeled neurons were observed in the hypothalamic paraventricular nucleus (PVN), lateral hypothalamus (LH), inferior olive (IO), and locus coeruleus (LC). No FG-positive cells were observed in the SN or striatum. Furthermore, after injection of anterograde tracer biotinylated dextran amine (BDA) into the SN, BDA-positive fibers were observed in the caudate putamen (Cpu), globus pallidus (GP), LC, and LH but not in the DVC. Conclusion: This study is the first to demonstrate that neurons in the SN do not directly innervate the DVC in rats. The DVC might be indirectly innervated by the SN through the hypothalamus and/or the LC. These data provide important morphological insights into the potential mechanism underlying the gastroparesis observed in PD patients. Show more

Keywords: Retrograde tracing, anterograde tracing, substantia nigra, dorsal vagus complex, gastroparesis

DOI: 10.3233/JPD-130279

Citation: Journal of Parkinson's Disease, vol. 4, no. 3, pp. 375-383, 2014