Journal of Parkinson's Disease - Volume 7, issue 2

Authors: Meijer, Frederick J.A. | Goraj, Bozena | Bloem, Bastiaan R. | Esselink, Rianne A.J.

Article Type: Review Article

Abstract: Background: Differentiating Parkinson’s disease and atypical parkinsonism on clinical parameters is challenging, especially in early disease courses. This is due to large overlap in symptoms and because the so called red flags, i.e. symptoms indicating atypical parkinsonism, have not (fully) developed. Brain MRI can aid to improve the accuracy and confidence about the diagnosis. Objective and Methods: In the current paper, we discuss when brain MRI should be performed in the diagnostic work-up of parkinsonism, our preferred brain MRI scanning protocol, and the diagnostic value of specific abnormalities. Results and Conclusions: The main purpose of …brain MRI is to assess cerebrovascular damage, and to exclude other possible – and sometimes treatable – causes of parkinsonism, such as normal pressure hydrocephalus. Furthermore, brain MRI can support the possible or probable diagnosis of a specific form of atypical parkinsonism. Show more

Keywords: Atypical parkinsonism, brain, magnetic resonance imaging, Parkinson’s disease

DOI: 10.3233/JPD-150733

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 211-217, 2017

Authors: Williams, Erin T. | Chen, Xi | Moore, Darren J.

Article Type: Review Article

Abstract: Mutations in the vacuolar protein sorting 35 ortholog (VPS35 ) gene encoding a core component of the retromer complex, have recently emerged as a new cause of late-onset, autosomal dominant familial Parkinson’s disease (PD). A single missense mutation, AspD620Asn (D620N), has so far been unambiguously identified to cause PD in multiple individuals and families worldwide. The exact molecular mechanism(s) by which VPS35 mutations induce progressive neurodegeneration in PD are not yet known. Understanding these mechanisms, as well as the perturbed cellular pathways downstream of mutant VPS35, is important for the development of appropriate therapeutic strategies. In this review, …we focus on the current knowledge surrounding VPS35 and its role in PD. We provide a critical discussion of the emerging data regarding the mechanisms underlying mutant VPS35-mediated neurodegeneration gleaned from genetic cell and animal models and highlight recent advances that may provide insight into the interplay between VPS35 and several other PD-linked gene products (i.e. α-synuclein, LRRK2 and parkin) in PD. Present data support a role for perturbed VPS35 and retromer function in the pathogenesis of PD. Show more

Keywords: VPS35, retromer, Parkinson’s disease (PD), endosomal sorting, mitochondria, autophagy, lysosome, α-synuclein, LRRK2, parkin

DOI: 10.3233/JPD-161020

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 219-233, 2017

Authors: Dayal, Viswas | Limousin, Patricia | Foltynie, Thomas

Article Type: Review Article

Abstract: Subthalamic Nucleus Deep Brain Stimulation (STN DBS) is a well-established and effective treatment modality for selected patients with Parkinson’s disease (PD). Since its advent, systematic exploration of the effect of stimulation parameters including the stimulation intensity, frequency, and pulse width have been carried out to establish optimal therapeutic ranges. This review examines published data on these stimulation parameters in terms of efficacy of treatment and adverse effects. Altering stimulation intensity is the mainstay of titration in DBS programming via alterations in voltage or current settings, and is characterised by a lower efficacy threshold and a higher side effect threshold which …define the therapeutic window. In addition, much work has been done in exploring the effects of frequency modulation, which may help patients with gait freezing and other axial symptoms. However, there is a paucity of data on the use of ultra-short pulse width settings which are now possible with technological advances. We also discuss current evidence for the use of novel programming techniques including directional and adaptive stimulation, and highlight areas for future research. Show more

Keywords: Deep brain stimulation (DBS), Parkinson’s Disease (PD), Subthalamic Nucleus (STN), electrical parameters

DOI: 10.3233/JPD-171077

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 235-245, 2017

Authors: Sakai, Waka | Nakane, Shunya | Urasaki, Eiichirou | Toyoda, Keisuke | Sadakata, Eisaku | Nagaishi, Akiko | Fukudome, Takayasu | Yamakawa, Yuzo | Matsuo, Hidenori

Article Type: Research Article

Abstract: Background: Camptocormia, a disturbance of posture, is a well-described clinical feature of PD and other parkinsonian syndromes. Previous reports have shown that DBS of the subthalamic nucleus (STN) or globus pallidus internus is effective in treating camptocormia. However, the efficacy of DBS for camptocormia varies. Objective: To determine a clinical marker for selecting an appropriate therapy for camptocormia, a disabling manifestation of Parkinson’s disease (PD) that has a variable response to systemic and local therapies. Methods: We obtained pre-operative lumbar magnetic resonance imaging of 14 consecutive PD patients with camptocormia who underwent subthalamic nucleus deep …brain stimulation (STN-DBS) in this retrospective-designed study. Lumbar MRI was performed three to six months prior to the operation. We measured the cross-sectional area (CSA) and width of each participant’s paraspinal muscles. Results: Four (28.6%) patients were effective (EF), five (35.7%) were partially effective (PE), and five (35.7%) were non-effective (NE) to STN-DBS. The lumbar paraspinal CSA and width were significantly larger in the EF group than in the PE and NE groups. Conclusions: The CSA of paraspinal muscles and erector spinae width can be good predictive markers for improving camptocormia in patients with PD after deep brain stimulation. Show more

Keywords: Parkinson’s disease, camptocormia, deep brain stimulation, subthalamic nucleus, posture, myopathic, paraspinal muscles, cross-sectional area, predictive markers, proprioception

DOI: 10.3233/JPD-160948

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 247-253, 2017

Authors: Coelho, Miguel | Abreu, Daisy | Correia-Guedes, Leonor | Lobo, Patricia Pita | Fabbri, Margherita | Godinho, Catarina | Domingos, Josefa | Albuquerque, Luisa | Freitas, Vanda | Pereira, João Miguel | Cattoni, Begona | Carvalho, Herculano | Reimão, Sofia | Rosa, Mário M. | Ferreira, António Gonalves | Ferreira, Joaquim J.

Article Type: Research Article

Abstract: Background: There is scarce data on the level of handicap in Parkinson’s disease (PD) and none in advanced stage PD. Objective: To assess the handicap in advanced stage PD patients with disabling levodopa-induced motor complications selected to deep brain stimulation (DBS). Methods: Data was prospectively recorded during routine evaluation for DBS. Handicap was measured using London Handicap Scale (LHS) (0 = maximal handicap; 1 = no handicap). Disease severity was evaluated using the Hoehn & Yahr scale and the UPDRS/MDS-UPDRS, during off and on after a supra-maximal dose of levodopa. Schwab and England Scale (S&E) was scored …in off and on . Dyskinesias were scored using the modified Abnormal Involuntary Movement Scale (mAIMS). Results concern cross-sectional assessment before DBS. Results: 100 PD patients (mean age 61 (±7.6); mean disease duration 12.20 (±4.6) years) were included. Median score of motor MDS-UPDRS was 54 in off and 25 in on. Mean total LHS score was 0.56 (±0.14). Patients were handicapped in several domains with a wide range of severity. Physical Independence and Social Integration were the most affected domains. Determinants of total LHS score were MDS-UPDRS part II off (β= –0.271; p  = 0.020), S&E on (β= 0.264; p  = 0.005) and off (β= 0.226; p  = 0.020), and mAIMS on (β= –0.183; p  = 0.042) scores (R2  = 29.6%). Conclusions: We were able to use handicap to measure overall health condition in advanced stage PD. Patients were moderately to highly handicapped and this was strongly determined by disability in ADL and dyskinesias. Change in handicap may be a good patient-centred outcome to assess efficiency of DBS. Show more

Keywords: Parkinson’s disease, advanced stage, handicap, London Handicap Scale, motor complications

DOI: 10.3233/JPD-160848

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 255-261, 2017

Authors: Ventorp, Filip | Bay-Richter, Cecilie | Nagendra, Analise Sauro | Janelidze, Shorena | Matsson, Viktor Sjödahl | Lipton, Jack | Nordström, Ulrika | Westrin, Åsa | Brundin, Patrik | Brundin, Lena

Article Type: Research Article

Abstract: Background: Exendin-4 is a peptide agonist of the glucagon-like peptide-1 (GLP-1) receptor, currently in clinical trials as a potential disease-modifying therapy for Parkinson’s disease. In light of this, it is important to understand potential modes of action of exendin-4 in the brain. Exendin-4 is neuroprotective and has been proposed to be directly anti-inflammatory, and that this is one way it reduces neurodegeneration. However, prior studies have focused on animal models involving both neurodegeneration and inflammation, therefore, it is also possible that the observed decreased inflammation is secondary to reduced neurodegeneration. Objective: To investigate whether exendin-4 directly reduces …inflammation in the brain following an insult that involves neuroinflammation but not neurodegeneration, namely systemic administration of lipopolysaccharide (LPS). Methods: Rats were administered LPS systemically and were treated with either 0.5 μg/kg exendin-4 or saline vehicle injections over 5 days. Behavior was evaluated with forced swim test. We assayed TNF-α and IL-1β levels in cerebrospinal fluid and cytokine mRNA expression in striatal, hippocampal and cortical tissues using qPCR. We determined brain monoamines using high-performance liquid chromatography. Finally, we isolated primary brain microglia from rats and measured cytokine production after exendin-4 treatment and LPS stimulation. Results: Exendin-4 treatment did not affect cytokine mRNA expression in brain, cytokine levels in cerebrospinal fluid or cytokine production from cultured microglia, although there was a trend towards increased striatal dopamine. Importantly, exendin-4 significantly prevented depressive-like behavior at 24 hours after LPS injection, indicating that the drug engaged a target in the brain. Depressive-like behavior was associated with altered dopamine turnover in the striatum. Conclusion: We did not detect any anti-inflammatory effects of exendin-4. In previous studies exploring the effects of exendin-4 on brain insults involving neurodegeneration, observations of reduced inflammation might have been secondary to mitigation of neuronal death. Our results indicate that the effects of exendin-4 on behavior may be due to effects on dopamine synthesis or metabolism. Show more

Keywords: Exendin-4, Parkinson’s disease, depression, dopamine, inflammation, cytokine, Brain

DOI: 10.3233/JPD-171068

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 263-273, 2017

Authors: Othman, Ahmed A. | Rosebraugh, Matthew | Chatamra, Krai | Locke, Charles | Dutta, Sandeep

Article Type: Short Communication

Abstract: In a double-blind, double-dummy, double-titration Phase 3 trial in advanced Parkinson’s disease (PD) patients, the efficacy and safety of Levodopa-carbidopa intestinal gel (LCIG) infusion were characterized relative to immediate-release oral levodopa-carbidopa (LC-oral) treatment. We present in this report the comparative pharmacokinetic profiles of LCIG and LC-oral from this pivotal study. The results presented in this report clearly demonstrate that LCIG results in lower variability and fluctuations in levodopa and carbidopa plasma concentrations compared to LC-oral. The superior pharmacokinetic profiles with LCIG were consistent with its improved efficacy compared to LC-oral as demonstrated in this study.

Keywords: Parkinson’s disease, levodopa/carbidopa intestinal gel, pharmacokinetics, movement disorders

DOI: 10.3233/JPD-161042

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 275-278, 2017

Authors: Hickey, Patrick T. | Kuchibhatla, Maragatha | Scott, Burton | Gauger, Lisa | Stacy, Mark A.

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is among the most prevalent neurodegenerative conditions. While motor and non-motor aspects of this disease have been well characterized, no objective biomarker exists to support an accurate clinical diagnosis. However, newer imaging techniques, including [123 I]-FP-CIT (DaTSCAN), have demonstrated utility in differentiating between PD and non-neurodegenerative tremor disorders. Objective: DaTSCAN has been primarily investigated in situations where diagnostic confusion exists, and in these instances has been shown to significantly impact clinical management. The goal of this pilot study was to evaluate the impact of DaTSCAN on the clinical management of patients with early …probable PD, where no diagnostic uncertainty exists. Methods: This was a prospective, 54-week, comparative pilot study, in which twenty subjects with de novo PD were randomly assigned to DaTSCAN either immediately upon diagnosis (and again at 6 and 12 months) or delayed to 6 months (and again at 12 months). The primary outcome measure was the frequency of deviation from the initial treatment plan from baseline to 54 weeks between the two groups. Secondary outcomes included motor and non-motor assessments. Results: There was no significant difference in the number of treatment changes over the course of the study between the two groups: initial imaging group = 4.2 (SD:2.74) vs. delayed imaging group = 2.3 (SD:2.0, p  = 0.11). In addition, there were no group differences in medication requirements, motor performance, or patient expectations of disease. Conclusions: In patients with early, probable PD, DaTSCAN contributes no additional impact on clinical management or functional outcomes when added to the diagnostic algorithm. Show more

Keywords: Biomarker, DaTSCAN, dopamine transporter, [123I]-FP-CIT, neuroimaging, Parkinson’s disease, SPECT

DOI: 10.3233/JPD-160937

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 279-287, 2017

Authors: Mischley, Laurie K. | Lau, Richard C. | Shankland, Eric G. | Wilbur, Timothy K. | Padowski, Jeannie M.

Article Type: Research Article

Abstract: Background: Reduced glutathione (GSH) is an endogenously synthesized tripeptide depleted early in the course of Parkinson’s disease (PD) and GSH augmentation has been proposed as a therapeutic strategy in PD. Objective: This Phase IIb study was designed to evaluate whether a Phase III study of intranasal GSH, (in)GSH, for symptomatic relief is warranted and to determine the most appropriate trial design for a disease-modification study. Methods: This was a double-blind, placebo-controlled trial of 45 individuals with Hoehn & Yahr Stage 1–3 PD. Participants were randomized to receive intranasal placebo (saline), 100 mg GSH, or 200 mg GSH …thrice daily for three months, and were observed over a one-month washout period. Results: All cohorts improved over the intervention period, including placebo. The high-dose group demonstrated improvement in total Unified PD Rating Scale (UPDRS) (–4.6 (4.7), P  = 0.0025) and UPDRS motor subscore (–2.2 (3.8), P  = 0.0485) over baseline, although neither treatment group was superior to placebo. One participant in the high-dose GSH cohort developed cardiomyopathy. Conclusions: Although predicted improvements in PD total and motor scores were observed, these data do not suggest (in)GSH is superior to placebo after a three month intervention. The symptomatic effects are sufficient to warrant a delayed-start or wash-out design study for disease-modification trials. Whether long-term use of (in)GSH leads to clinical improvements that are sustained and significantly different than placebo will require appropriately-powered longer-duration studies in larger cohorts. The improvement in the placebo arm was more robust than has been observed in previous PD studies and warrants further investigation. Show more

Keywords: Nutrition, nutritional, deficiency, nutrient, vitamin, neurodegenerative, neurodegeneration, neuroprotection

DOI: 10.3233/JPD-161040

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 289-299, 2017

Authors: Georgiopoulos, Charalampos | Warntjes, Marcel | Dizdar, Nil | Zachrisson, Helene | Engström, Maria | Haller, Sven | Larsson, Elna-Marie

Article Type: Research Article

Abstract: Background: Olfactory impairment is an early manifestation of Parkinson’s disease (PD). Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) are two imaging techniques that allow noninvasive detection of microstructural changes in the cerebral white matter. Objective: To assess white matter alterations associated with olfactory impairment in PD, using a binary imaging approach with DTI and MT. Methods: 22 PD patients and 13 healthy controls were examined with DTI, MT and an odor discrimination test. DTI data were first analyzed with tract-based spatial statistics (TBSS) in order to detect differences in fractional anisotropy, mean, radial and …axial diffusivity between PD patients and controls. Voxelwise randomized permutation was employed for the MT analysis, after spatial and intensity normalization. Additionally, ROI analysis was performed on both the DTI and MT data, focused on the white matter adjacent to olfactory brain regions. Results: Whole brain voxelwise analysis revealed decreased axial diffusivity in the left uncinate fasciculus and the white matter adjacent to the left olfactory sulcus of PD patients. ROI analysis demonstrated decreased axial diffusivity in the right orbitofrontal cortex, as well as decreased mean diffusivity and axial diffusivity in the white matter of the left entorhinal cortex of PD patients. There were no significant differences regarding fractional anisotropy, radial diffusivity or MT between patients and controls. Conclusions: ROI analysis of DTI could detect microstructural changes in the white matter adjacent to olfactory areas in PD patients, whereas MT imaging could not. Show more

Keywords: Parkinson disease, smell, diffusion tensor imaging, magnetization transfer contrast imaging

DOI: 10.3233/JPD-161060

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 301-311, 2017

Authors: Almeida, Lorena R.S. | Valenca, Guilherme T. | Negreiros, Nádja N. | Pinto, Elen B. | Oliveira-Filho, Jamary

Article Type: Research Article

Abstract: Background: Falls are a debilitating problem for people with Parkinson’s disease (PD). Objectives: To compare clinical and functional characteristics of non-fallers, single and recurrent fallers (≥2 falls); to determine predictors of time to second fall; and to develop a predictive tool for identifying people with PD at different categories of falls risk. Methods: Participants (n  = 229) were assessed by disease-specific, self-report and balance measures and followed up for 12 months. Area under the receiver operating characteristic curves (AUC), Kaplan-Meier curves and log-rank test were performed. Selected predictors with p  < 0.10 in univariate analysis were chosen …to be entered into the Cox regression model. Results: Eighty-four (37%) participants had ≥2 falls during the follow-up. Recurrent fallers significantly differed from single fallers. The final Cox model included history of ≥2 falls in the past year (Hazard Ratio [HR] = 3.94; 95% confidence interval [CI] 2.26–6.86), motor fluctuations (HR = 1.91; 95% CI 1.12–3.26), UPDRS activities of daily living (ADL) (HR = 1.10 per 1 point increase; 95% CI 1.06–1.14) and levodopa equivalent dose (LED) (HR = 1.09 per 100 mg increase; 95% CI 1.02–1.16). A 3-predictor tool included history of ≥2 falls in the past year, motor fluctuations and UPDRS ADL >12 points (AUC = 0.84; 95% CI 0.78–0.90). By adding LED >700 mg/day and Berg balance scale ≤49 points, a 5-predictor tool was developed (AUC = 0.86; 95% CI 0.81–0.92). Conclusions: Two predictive tools with moderate-to-high accuracy may identify people with PD at low, medium and high risk of falling recurrently within the next year. However, future studies to address external validation are required. Show more

Keywords: Parkinson disease, accidental falls, postural balance, risk factors

DOI: 10.3233/JPD-160934

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 313-324, 2017

Authors: Ossig, Christiana | Sippel, Daniel | Fauser, Mareike | Gandor, Florin | Jost, Wolfgang H. | Ebersbach, Georg | Storch, Alexander

Article Type: Research Article

Abstract: Background: Nonmotor symptoms (NMS) are known to fluctuate together with motor oscillations in advanced PD, but their timing and kinetics remains enigmatic. Objective: To evaluate timing and kinetics of NMS fluctuations. Methods: Analysis of diary data from 17 fluctuating PD patients. Diaries were completed by rating NMS as absent (defined herein as NMS On state) or present (NMS Off state) and motor function for every hour for 5 consecutive days. Timing and kinetics were analyzed by synchronizing motor Off periods and subsequent cross-classification of NMS Off periods for each motor Off hour into 2×2 contingency …tables. Results: We found clear temporal connections of NMS Off periods with motor Off periods only for anxiety/depression, concentration/attention deficiency and bladder urgency. Psychiatric NMS Off periods had a longer duration (median: 3–4 hours) compared to motor Off periods (2 hours; P  < 0.05, Mann-Whitney U-test). Conclusions: Our data on timing and kinetics of NMS fluctuations show close temporal connection with motor Off periods only for mood and cognitive symptoms. Variances in both timing and/or kinetics of NMS fluctuations might explain both the weak/absent correlations of NMS and motor symptom severity in fluctuating patients and the rather low rates of simultaneous switches between On and Off states for NMS and motor function. Show more

Keywords: Nonmotor symptoms, nonmotor fluctuations, timing, kinetics, motor complications, psychiatric symptoms, autonomic dysfunction, Parkinson’s disease

DOI: 10.3233/JPD-160996

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 325-330, 2017

Authors: Engen, Phillip A. | Dodiya, Hemraj B. | Naqib, Ankur | Forsyth, Christopher B. | Green, Stefan J. | Voigt, Robin M. | Kordower, Jeffrey H. | Mutlu, Ece A. | Shannon, Kathleen M. | Keshavarzian, Ali

Article Type: Research Article

Abstract: Background: Recent evidence suggests that Parkinson’s disease (PD) is associated with intestinal microbiota dysbiosis, abnormal intestinal permeability, and intestinal inflammation. Objective: Our study aimed to determine if these gut abnormalities are present in another synucleinopathy, multiple system atrophy (MSA). Methods: In six MSA and 11 healthy control subjects, we performed immunohistochemistry studies of colonic sigmoid mucosa to evaluate the intestinal barrier marker Zonula Occludens-1 and the endotoxin-related inflammation marker Toll-like-receptor-4 expression. We also assessed colonic sigmoid mucosal and fecal microbiota compositions using high-throughput 16S ribosomal RNA gene amplicon sequencing. Results: MSA subjects showed …disrupted tight junction protein Zonula Occludens-1 structure in sigmoid mucosa tissue suggesting intestinal barrier dysfunction. The lipopolysaccharide specific inflammatory receptor Toll-like-receptor-4 was significantly higher in the colonic sigmoid mucosa in MSA relative to healthy controls. Microbiota analysis suggested high relative abundance of gram-negative, putative “pro-inflammatory” bacteria in various family and genus level taxa, from the phylum Bacteroidetes and Proteobacteria, in MSA feces and mucosa. At the taxonomic level of genus, putative “anti-inflammatory” butyrate-producing bacteria were less abundant in MSA feces. Predictive functional analysis indicated that the relative abundance of a number of genes involved in metabolism were lower in MSA feces, whereas the relative abundance of genes involved in lipopolysaccharide biosynthesis were higher in both MSA feces and mucosa compared to healthy controls. Conclusions: This proof-of-concept study provides preliminary evidence that like PD, MSA subjects display evidence of disrupted intestinal barrier integrity, increased marker of endotoxin-related intestinal inflammation, and pro-inflammatory colonic microbiota. Show more

Keywords: Multiple system atrophy, microbiota, colonic mucosa and feces, lipopolysaccharide, Zonula Occludens-1, Tolllike-receptor-4

DOI: 10.3233/JPD-160991

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 331-346, 2017

Authors: Yilmaz, Rezzak | Bayram, Ece | Ulukan, Çağrı | Altınok, Mustafa Kemal | Akbostancı, Muhittin Cenk

Article Type: Research Article

Abstract: Background: It has been suggested that appendectomy may modify the emergence of Parkinson’s disease (PD) by affecting the retrograde transport of α-synuclein (α-syn) from the gastrointestinal system. Objective: To explore the possible role of appendectomy on PD. Methods: The retrospective data of the 1625 patients (839 PD, 633 non-α-syn parkinsonism and 153 controls) were compared. Disease specific measures between PD patients with (n  = 69) and without (n  = 770) appendectomy were also evaluated. Results: The prevalence of appendectomy was not significantly lower in the PD group (8.2%) compared to the other groups (8.4% and …7.9%, p  = 0.98), and the odds of having PD against other diagnoses (OR) were not significantly different in the appendectomy group (OR = 0.99, p  = 0.96). No difference was determined between PD patients with and without appendectomy with respect to the age of disease onset, disease duration and severity. Appendectomy-first symptom interval was not determined to be related with PD diagnosis (hazard ratio = 1.12, p  = 0.39) and did not predict disease severity in the PD group (OR = 0.99, p  = 0.54). Age of appendectomy (lower or higher than 20) also did not affect future PD diagnosis (Relative Risk = 0.9, p  = 0.54) or the disease severity. Conclusions: The results of the study suggest no effect of appendectomy on the emergence and clinical manifestations of PD. The removal of the appendix is possibly not sufficient to suppress the exposure of the brain stem to α-syn via vagal retrograde transport. Further studies are needed to elucidate the role of appendix in PD. Show more

Keywords: Parkinson’s disease, appendectomy

DOI: 10.3233/JPD-171071

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 347-352, 2017

Authors: Mishima, Takayasu | Fukae, Jiro | Fujioka, Shinsuke | Inoue, Kotoe | Tsuboi, Yoshio

Article Type: Research Article

Abstract: Background: Gastrointestinal symptoms are one of the most common non-motor features of Parkinson’s disease (PD). Recently, a report from Taiwan revealed that irritable bowel syndrome (IBS) may be associated with an increased risk of developing PD; however, the prevalence of IBS in PD patients has not been fully evaluated. Rome III criteria are widely assessed with a questionnaire to determine functional gastrointestinal disorders. Objective: We assessed the prevalence of constipation and IBS in PD patients in our cohort using Rome III criteria. Methods: Between October 2014 and April 2015, 118 patients with PD were treated …at Fukuoka University Hospital and were enrolled in this study. Rome III criteria were used to diagnose constipation and IBS. Results: Constipation and IBS were detected in 32 (27.1%) and 20 patients (17.0%), respectively. The most common symptom related to constipation was straining during defecation (77.1%). Among constipation symptoms, patients’ self-awareness of constipation was mostly related to straining during defecation (odds ratio 5.27, 95% confidence interval 1.475–18.811). The number of constipation symptoms was correlated with the severity of the Hoehn-Yahr Stage (p  < 0.05) and total levodopa equivalent dose (p  < 0.05). Conclusions: This is the first report to investigate the prevalence of IBS in PD patients with Rome III criteria. We found a higher prevalence of IBS compared with the general population. The prevalence of constipation based on Rome III criteria was much lower than that reported in previous studies. Further studies are warranted to evaluate gastrointestinal symptoms in PD patients using comparable questionnaires. Show more

Keywords: Constipation, irritable bowel syndrome, Parkinson’s disease, Rome III diagnostic criteria

DOI: 10.3233/JPD-160982

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 353-357, 2017

Authors: Knudsen, Karoline | Fedorova, Tatyana D. | Bekker, Anne C. | Iversen, Peter | Østergaard, Karen | Krogh, Klaus | Borghammer, Per

Article Type: Research Article

Abstract: Background: Gastrointestinal function has received increased interest in the context of Parkinson’s disease (PD). Constipation is among the most frequent non-motor symptoms, but our understanding of the underlying pathology is limited. Subjective constipation correlates poorly with objective markers. Objective: The aims were to evaluate colonic transit time and volume in PD and to correlate these measures with subjective symptoms and gastric emptying. Methods: Thirty-two PD patients and 26 controls were included. Colonic transit time, computed tomography-based volume estimation, and gastric emptying were performed as objective markers of gastrointestinal function. Subjective gastrointestinal symptoms were evaluated by …three different questionnaires. Results: Seventy-nine percent of PD patients displayed prolonged colonic transit time (p  < 0.0001) and 66% of patients had significantly increased colonic volume (p  = 0.0002). Particularly the transverse and rectosigmoid segments were affected. There was no difference in gastric emptying time between groups. The prevalence of subjective constipation in PD patients was significantly lower and ranged from 3% to 38% depending on the type of questionnaire. Conclusions: Significantly delayed colonic transit time and increased volume were frequent findings in PD patients, and objective dysfunction was considerably more prevalent than subjective constipation symptoms. Also, the prevalence of subjective constipation varied widely depending upon which questionnaire was employed. These findings highlight the need for more research on how to define constipation in PD and also the need for improved understanding of the relationship between subjective symptoms and objective dysfunction. Show more

Keywords: Parkinson, constipation, gastrointestinal, non-motor symptom, transit time

DOI: 10.3233/JPD-161050

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 359-367, 2017

Authors: Ryu, Dong-Woo | Lee, Si-Hoon | Oh, Yoon-Sang | An, Jae-Young | Park, Jeong-Wook | Song, In-Uk | Lee, Kwang-Soo | Kim, Joong-Seok

Article Type: Research Article

Abstract: Background: Recent genetic and epidemiological studies have shown that there is a link between essential tremor and Parkinson’s disease (PD). However, there is a lack of data about the clinical features of PD developed from essential tremor. Objective: To explore and describe the clinical characteristics of Parkinson’s disease developed from essential tremor (ET-PD). Methods: Twenty-five ET-PD patients and 124 IPD controls were enrolled according to each criterion. Motor and non-motor features and dopamine transporter uptake were compared between the two groups. Results: Rest and action tremors were more severe in ET-PD patients than …in IPD patients. In addition, tremor disorder of first-degree relatives occurred more frequently in the ET-PD group than in the IPD group. A comparison between cases with ET-PD and IPD was not significant for striatal dopamine transporter uptake. Among the non-motor features, sleep disorder frequency, especially rapid-eye-movement sleep behavioral disorder, were lower in patients with ET-PD than in those with IPD, and smell identification test scores were higher in patients with ET-PD than in those with IPD. The prevalence of other non-motor symptoms did not differ between the two groups. Conclusion: This is the first comparison of motor and non-motor features between ET-PD and IPD. ET-PD and IPD have different characteristic motor and non-motor features from the nosologic perspective. Show more

Keywords: Parkinson’s disease, essential tremor, non-motor symptoms, REM sleep behavior disorder, olfactory dysfunction

DOI: 10.3233/JPD-160992

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 369-376, 2017

Authors: Kelley, Kristen D. | Peavy, Guerry | Edland, Steven | Rogers, Whitney | Riley, David E. | Bordelon, Yvette | Standaert, David | Reich, Stephen G. | Litvan, Irene

Article Type: Research Article

Abstract: Background: PSP, like Alzheimer’s disease (AD), is a tauopathy. The etiopathogenesis of PSP is not well known and the role of stress has not yet been examined. Recent studies have shown that stress increases the risk for developing AD. This study investigates the role of stress as a risk factor for PSP. Objective: B To examine the association between the development of progressive supranuclear palsy (PSP) and self-reported life stressors. Methods: 76 patients diagnosed with PSP according to the NINDS-SPSP criteria and 68 age-matched unrelated controls were administered a life stressor questionnaire. Stress was quantified …as total number of events, number of life changing events, and number of events characterized by self-rated severity. Conditional odds ratio (OR) was calculated for each measure, with participants in the highest quartile of each measure being defined as high-exposure in relation to all other participants. Results: There were no significant differences between the reported number of total events or life-changing events in cases and controls. However, we found 24.4% of cases (N = 11) and 9.1% of controls (N = 5) had a higher exposure to high severity events, yielding an OR of 3.2 (p  = 0.04). Conclusions: We found that cases have over a three times greater odds of high exposure to high-severity events than controls prior to the clinical development of PSP, while there were no differences in overall number of reported events. Our findings suggest that high exposure to highly stressful events may be associated with the development of PSP. Show more

Keywords: Progressive supranuclear palsy (PSP), stress, epidemiology, case-control

DOI: 10.3233/JPD-160945

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 377-383, 2017

Authors: Brennan, Laura | Devlin, Kathryn M. | Xie, Sharon X. | Mechanic-Hamilton, Dawn | Tran, Baochan | Hurtig, Howard H. | Chen-Plotkin, Alice | Chahine, Lama M. | Morley, James F. | Duda, John E. | Roalf, David R. | Dahodwala, Nabila | Rick, Jacqueline | Trojanowski, John Q. | Moberg, Paul J. | Weintraub, Daniel

Article Type: Research Article

Abstract: Background: Methods to detect early cognitive decline and account for heterogeneity of deficits in Parkinson’s disease (PD) are needed. Quantitative methods such as latent class analysis (LCA) offer an objective approach to delineate discrete phenotypes of impairment. Objective: To identify discrete neurocognitive phenotypes in PD patients without dementia. Methods: LCA was applied to a battery of 8 neuropsychological measures to identify cognitive subtypes in a cohort of 199 non-demented PD patients. Two measures were analyzed from each of four domains: executive functioning, memory, visuospatial abilities, and language. Additional analyses compared groups on clinical characteristics and …cognitive diagnosis. Results: LCA identified 3 distinct groups of PD patients: an intact cognition group (54.8%), an amnestic group (32.2%), and a mixed impairment group with dysexecutive, visuospatial and lexical retrieval deficits (13.1%). The two impairment groups had significantly lower instrumental activities of daily living ratings and greater motor symptoms than the intact group. Of those diagnosed as cognitively normal according to MDS criteria, LCA classified 23.2% patients as amnestic and 9.9% as mixed cognitive impairment. Conclusions: Non-demented PD patients exhibit distinct neuropsychological profiles. One-third of patients with LCA-determined impairment were diagnosed as cognitively intact by expert consensus, indicating that classification using a statistical algorithm may improve detection of initial and subtle cognitive decline. This study also demonstrates that memory impairment is common in non-demented PD even when cognitive impairment is not clinically apparent. This study has implications for predicting eventual emergence of significant cognitive decline, and treatment trials for cognitive dysfunction in PD. Show more

Keywords: Parkinson’s disease, cognition, latent class analysis, neuropsychology

DOI: 10.3233/JPD-171081

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 385-395, 2017

Authors: Kader, Manzur | Ullén, Susann | Iwarsson, Susanne | Odin, Per | Nilsson, Maria H.

Article Type: Research Article

Abstract: Background: While walking difficulties are common in people with Parkinson’s disease (PD), little is known about factors that independently contribute to their perceived walking difficulties. Objective: To identify factors that independently contribute to perceived walking difficulties in people with PD. Methods: This study involved 243 (62% men) participants; their mean (min-max) age and PD duration were 70 (45–93) and 8 (1–43) years, respectively. A postal survey preceded a home visit that included observations, clinical tests, questions and questionnaires that were administered as a structured interview. Perceived walking difficulties (dependent variable) were assessed with the self-administered …generic Walk-12 (Walk-12G, scored 0–42, higher = worse). Independent variables included personal (e.g., age and general self-efficacy) and social environmental factors (e.g., social support and living situation) as well as disease-related factors including motor (e.g., freezing of gait (FOG) and postural instability) and non-motor symptoms (e.g., fatigue and orthostatic hypotension). Linear multiple regression analysis was used to identify factors that independently contributed to perceived walking difficulties. Results: Eight significant independent variables explained 56.3% of the variance in perceived walking difficulties. FOG was the strongest significant contributing factor to perceived walking difficulties, followed by general self-efficacy, fatigue, PD duration, lower extremity function, orthostatic hypotension, bradykinesia and postural instability. Conclusion : Motor and non-motor symptoms as well as personal factors (i.e., general self-efficacy) seem to be of importance for perceived walking difficulties in PD. These findings might nurture future interventions that address modifiable factors in order to enhance walking ability in people with PD. Show more

Keywords: Difficulty walking, fatigue, Parkinson Disease, patient outcome assessment, regression analysis, self-efficacy

DOI: 10.3233/JPD-161034

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 397-407, 2017