Journal of Parkinson's Disease - Volume 12, issue 4

Authors: Chen, Szu-Ju | Chen, Chieh-Chang | Liao, Hsin-Yu | Wu, Yu-Wei | Liou, Jyh-Ming | Wu, Ming-Shiang | Kuo, Ching-Hua | Lin, Chin-Hsien

Article Type: Research Article

Abstract: Background: Emerging evidence suggests that gut dysbiosis contributes to Parkinson’s disease (PD) by signaling through microbial metabolites. Hippuric acid (HA), indole derivatives, and secondary bile acids are among the most common gut metabolites. Objective: To examine the relationship of systemic concentrations of these microbial metabolites associated with changes of gut microbiota, PD status, and severity of PD. Methods: We enrolled 56 patients with PD and 43 age- and sex-matched healthy participants. Motor and cognitive severity were assessed with Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III motor score and the Mini-Mental State Examination (MMSE), …respectively. Plasma concentrations of targeted gut metabolites were measured with liquid chromatography-tandem mass spectrometry. Gut microbiota was analyzed with shotgun metagenomic sequencing. Results: Compared with controls, PD patients had significantly higher plasma levels of HA, indole-3-propionic acid (IPA), deoxycholic acid (DCA), and glycodeoxycholic acid (GDCA). After adjustment for age and sex in a multivariate logistic regression analysis, plasma levels of HA (odds ratio [OR] 3.21, p  < 0.001), IPA (OR 2.59, p  = 0.031), and GDCA (OR 2.82, p  = 0.036) were associated with positive PD status. Concentrations of these gut metabolites did not correlate with MDS-UPDRS part III score or MMSE after adjustment for confounders. Microbial metabolite levels were associated with the relative abundance of pro-inflammatory gut bacteria. Conclusion: Aberrant gut microbial metabolites of HA, indole derivatives and secondary bile acids associated with specific gut microbiota changes were observed in patients with PD. Show more

Keywords: Parkinson’s disease, microbial metabolite, gut microbiota, gut–brain axis, bile acid, hippuric acid, indole derivative

DOI: 10.3233/JPD-223179

Citation: Journal of Parkinson's Disease, vol. 12, no. 4, pp. 1219-1230, 2022

Authors: Brezovar, Simon | Pažek, Lucija | Kavčič, Martin | Georgiev, Dejan | Trošt, Maja | Flisar, Dušan

Article Type: Research Article

Abstract: Background: While deep brain stimulation of the subthalamic nucleus (STN-DBS) significantly improves motor deficits in patients with Parkinson’s disease (PD), it is still unclear whether it affects personality functioning. Objective: The objective of the present study was to examine personality changes in patients with PD after STN-DBS from the perspectives of both the patients and caregivers. Moreover, by assessing the premorbid personalities of the patients, we tried to determine individual vulnerability to STN-DBS-induced personality changes. Methods: In total, 27 patients and their caregivers participated in our retrospective observational study. They were asked to assess the patients’ …personality changes with the Iowa Scale of Personality Changes (ISPC) and the patients’ premorbid personalities with the Big Five Inventory (BFI). Results: Caregivers reported significant personality changes in the ISPC domains of Executive Disturbance (p  = 0.01) and Disturbed Social Behavior (p  = 0.02). Most of the ISPC domains were positively correlated with Conscientiousness, while Executive Disturbance was negatively correlated with Neuroticism of the BFI scale. Conclusion: Our results show that executive and social functioning are the two most vulnerable domains in patients with PD after STN-DBS, especially in those patients who score higher for neuroticism and lower for conscientiousness on the BFI scale. The results of our study may provide movement disorder specialists with better counseling options and better selection of DBS candidates. Caregivers’ perspective might contribute significantly in understanding postoperative personality changes. Show more

Keywords: Parkinson’s disease, deep brain stimulation, personality changes

DOI: 10.3233/JPD-212879

Citation: Journal of Parkinson's Disease, vol. 12, no. 4, pp. 1231-1240, 2022

Authors: Lench, Daniel H. | Keith, Kathryn | Wilson, Sandra | Padgett, Lucas | Benitez, Andreana | Ramakrishnan, Viswanathan | Jensen, Jens H. | Bonilha, Leonardo | Revuelta, Gonzalo J.

Article Type: Research Article

Abstract: Background: Background: Parkinson’s disease (PD) patients who develop freezing of gait (FOG) have reduced mobility and independence. While some patients experience improvement in their FOG symptoms with dopaminergic therapies, a subset of patients have little to no response. To date, it is unknown what changes in brain structure underlie dopa-response and whether this can be measured using neuroimaging approaches. Objective: We tested the hypothesis that structural integrity of brain regions (subthalamic nucleus and globus pallidus internus, GPi) which link basal ganglia to the mesencephalic locomotor region (MLR), a region involved in automatic gait, would be associated with …FOG response to dopaminergic therapy. Methods: In this observational study, thirty-six participants with PD and definite FOG were recruited to undergo diffusion kurtosis imaging (DKI) and multiple assessments of dopa responsiveness (UPDRS scores, gait times ON versus OFF medication). Results: The right GPi in participants with dopa-unresponsive FOG showed reduced fractional anisotropy, mean kurtosis (MK), and increased radial diffusivity relative to those with dopa-responsive FOG. Furthermore, using probabilistic tractography, we observed reduced MK and increased mean diffusivity along the right GPi-MLR tract in dopa-unresponsive FOG. MK in the right GPi was associated with a subjective dopa-response for FOG (r  = –0.360, df = 30, p  = 0.043) but not overall motor dopa-response. Conclusion: These results support structural integrity of the GPi as a correlate to dopa-response in FOG. Additionally, this study suggests DKI metrics may be a sensitive biomarker for clinical studies targeting dopaminergic circuitry and improvements in FOG behavior. Show more

Keywords: Freezing, Parkinson’s disease, connectivity, neuroimaging, gait, dopamine, tractography, L-DOPA

DOI: 10.3233/JPD-213062

Citation: Journal of Parkinson's Disease, vol. 12, no. 4, pp. 1241-1250, 2022

Authors: Strelow, Joshua N. | Baldermann, Juan C. | Dembek, Till A. | Jergas, Hannah | Petry-Schmelzer, Jan N. | Schott, Frederik | Dafsari, Haidar S. | Moll, Christian K.E. | Hamel, Wolfgang | Gulberti, Alessandro | Visser-Vandewalle, Veerle | Fink, Gereon R. | Pötter-Nerger, Monika | Barbe, Michael T.

Article Type: Research Article

Abstract: Background: Freezing of gait (FOG) is among the most common and disabling symptoms of Parkinson’s disease (PD). Studies show that deep brain stimulation (DBS) of the subthalamic nucleus (STN) can reduce FOG severity. However, there is uncertainty about pathways that need to be modulated to improve FOG. Objective: To investigate whether STN-DBS effectively reduces FOG postoperatively and whether structural connectivity of the stimulated tissue explains variance of outcomes. Methods: We investigated 47 patients with PD and preoperative FOG. Freezing prevalence and severity was primarily assessed using the Freezing of Gait Questionnaire (FOG-Q). In a subset of …18 patients, provoked FOG during a standardized walking course was assessed. Using a publicly available model of basal-ganglia pathways we determined stimulation-dependent connectivity associated with postoperative changes in FOG. A region-of-interest analysis to a priori defined mesencephalic regions was performed using a disease-specific normative connectome. Results: Freezing of gait significantly improved six months postoperatively, marked by reduced frequency and duration of freezing episodes. Optimal stimulation volumes for improving FOG structurally connected to motor areas, the prefrontal cortex and to the globus pallidus. Stimulation of the lenticular fasciculus was associated with worsening of FOG. This connectivity profile was robust in a leave-one-out cross-validation. Subcortically, stimulation of fibers crossing the pedunculopontine nucleus and the substantia nigra correlated with postoperative improvement. Conclusion: STN-DBS can alleviate FOG severity by modulating specific pathways structurally connected to prefrontal and motor cortices. More differentiated FOG assessments may allow to differentiate pathways for specific FOG subtypes in the future. Show more

Keywords: Basal-ganglia pathways, deep brain stimulation, dorsolateral prefrontal cortex, freezing of gait, Freezing of Gait Questionnaire, globus pallidus, lenticular fasciculus, nucleus subthalamicus, supplementary motor area, Unified Parkinson’s Disease Rating Scale

DOI: 10.3233/JPD-212997

Citation: Journal of Parkinson's Disease, vol. 12, no. 4, pp. 1251-1267, 2022

Authors: Vinke, R. Saman | Selvaraj, Ashok K. | Geerlings, Martin | Georgiev, Dejan | Sadikov, Aleksander | Kubben, Pieter L. | Doorduin, Jonne | Praamstra, Peter | Bloem, Bastiaan R. | Bartels, Ronald H.M.A. | Esselink, Rianne A.J.

Article Type: Research Article

Abstract: Background: Bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) has become a cornerstone in the advanced treatment of Parkinson’s disease (PD). Despite its well-established clinical benefit, there is a significant variation in the way surgery is performed. Most centers operate with the patient awake to allow for microelectrode recording (MER) and intraoperative clinical testing. However, technical advances in MR imaging and MRI-guided surgery raise the question whether MER and intraoperative clinical testing still have added value in DBS-surgery. Objective: To evaluate the added value of MER and intraoperative clinical testing to determine final lead position in awake …MRI-guided and stereotactic CT-verified STN-DBS surgery for PD. Methods: 29 consecutive patients were analyzed retrospectively. Patients underwent awake bilateral STN-DBS with MER and intraoperative clinical testing. The role of MER and clinical testing in determining final lead position was evaluated. Furthermore, interobserver variability in determining the MRI-defined STN along the planned trajectory was investigated. Clinical improvement was evaluated at 12 months follow-up and adverse events were recorded. Results: 98% of final leads were placed in the central MER-track with an accuracy of 0.88±0.45 mm. Interobserver variability of the MRI-defined STN was 0.84±0.09. Compared to baseline, mean improvement in MDS-UPDRS-III, PDQ-39 and LEDD were 26.7±16.0 points (54%) (p  < 0.001), 9.0±20.0 points (19%) (p  = 0.025), and 794±434 mg/day (59%) (p  < 0.001) respectively. There were 19 adverse events in 11 patients, one of which (lead malposition requiring immediate postoperative revision) was a serious adverse event. Conclusion: MER and intraoperative clinical testing had no additional value in determining final lead position. These results changed our daily clinical practice to an asleep MRI-guided and stereotactic CT-verified approach. Show more

Keywords: Deep brain stimulation, microelectrode recording, MRI-guided, subthalamic nucleus, Parkinson’s disease

DOI: 10.3233/JPD-223149

Citation: Journal of Parkinson's Disease, vol. 12, no. 4, pp. 1269-1278, 2022

Authors: Dash, Deepa | Cote, Diane | Conway, Jennifer | Grimes, David | Mestre, Tiago A.

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder with a myriad of motor and non-motor symptoms. Although deep brain stimulation (DBS) has a dramatic impact in the lives of people with PD, care delivery remains complex. There is a lack of evidence on the implementation and role of integrated care and self-management support in people with PD and chronic DBS. Objective: To evaluate care needs, implementation and impact of a pragmatic network for PD care, the Integrated Parkinson Care Network (IPCN) in people with PD and chronic DBS. Methods: This is a subgroup analyses of …a 6-month, pre–post design, single-centre, phase 2 study to assess a patient-centred care model based on integrated care, self-management support in PD (IPCN), focusing on those participants with chronic DBS. Results: We included 22 people with PD and chronic DBS (median time since DBS - 30 months). The mean age was 63.9 (7.6) years and mean disease duration was 15.2 (6.9) years. The top three care priorities were speech (54.5%), mobility (40.9%) and mood (31.8%). After the IPCN program, there was a positive change in the perception of support for chronic care (Patient Assessment of Chronic Illness Care +: –0.84; 95% CI: –1.2 to –0.5) and self-management (5As: –0.77; 95% CI: –1.1 to –0.4), along with quality of life (PDQ8 : 7.1, 95% CI:1.8 –12.4). Conclusion: The IPCN is a care delivery model that addresses specific care needs of people with PD and chronic DBS. The current study showed its feasibility and warrants further evaluation. Show more

Keywords: Parkinson’s disease, deep brain stimulation, care, quality of life

DOI: 10.3233/JPD-212911

Citation: Journal of Parkinson's Disease, vol. 12, no. 4, pp. 1279-1284, 2022

Authors: Van Hienen, Marle M. | Kuiper, Roy | Middelkoop, Huub A.M. | Van Hilten, Jacobus J. | Contarino, Maria Fiorella | Geraedts, Victor J.

Article Type: Research Article

Abstract: Background: Caregivers of Parkinson’s disease (PD) patients provide important support during the pre- and postoperative phase of deep brain stimulation (DBS). High levels of caregiver burden have been reported after DBS. However, a comparison between preoperative and postoperative burden and associated factors has been insufficiently studied. Objective: To investigate the influence of DBS on caregiver burden, and to identify the differential impact of patient-related factors on caregiver burden before and after DBS. Methods: Consecutive patients referred for DBS eligibility screening or during one-year follow-up assessments were included. Caregiver burden was measured with the short Zarit Burden …Interview (ZBI-12). Inverse Probability Weighting (IPW) was used to compare caregiver burden between preoperative and postoperative assessments. Results: We included 47 patients (24 screening, 23 follow-up) (median age 65 years, 29.4% female sex). DBS did not impact caregiver burden (screening: median ZBI-12 9.5 (IQR 3.25, 16.75); follow-up median ZBI-12 6 (IQR 4, 14); IPW-coefficient 0.57 (95% CI –2.75, 3.89)). Worse caregiver burden during DBS screening was associated with worse patient-related scores on depressive symptoms, anxiety, QoL, and impulsiveness. Worse scores on depressive symptoms, anxiety, apathy, postural-instability-gait-disorder, and QoL were associated with worse caregiver burden at one-year follow-up. Conclusion: DBS appears not associated with changes in caregiver burden. Various symptoms are valued differently between screening and follow-up assessments in terms of caregiver burden. Early recognition of caregivers “at risk” may improve guidance of patient-caregiver dyads throughout the DBS process. Show more

Keywords: Parkinson’s disease, caregiver burden, deep brain stimulation, quality of life, epidemiology

DOI: 10.3233/JPD-213093

Citation: Journal of Parkinson's Disease, vol. 12, no. 4, pp. 1285-1293, 2022

Authors: Oonk, Nicol G.M. | Movig, Kris L.L. | van der Palen, Job | Nibourg, Simone A.F. | Koehorst-ter Huurne, Kirsten | Nijmeijer, Henk-Willem | van Kesteren, Mirjam E. | Dorresteijn, Lucille D.A.

Article Type: Research Article

Abstract: Background: Drug therapy is important for controlling symptoms in Parkinson’s disease (PD). However, it often results in complex medication regimens and could easily lead to drug related problems (DRP), suboptimal adherence and reduced treatment efficacy. A structured medication review (SMR) could address these issues and optimize therapy, although little is known about clinical effects in PD patients. Objective: To analyze whether an SMR improves quality of life (QoL) in PD. Methods: In this multicenter randomized controlled trial, half of the 202 PD patients with polypharmacy received a community pharmacist-led SMR. The control group received usual care. …Assessments at baseline, and after three and six months comprised six validated questionnaires. Primary outcome was PD specific QoL [(PDQ-39; range 0 (best QoL) – 100 (worst QoL)]. Secondary outcomes were disability score, non-motor symptoms, general health status, and personal care giver’s QoL. Furthermore, DRPs, proposed interventions, and implemented modifications in medication schedules were analyzed. Results: No improvement in QoL was seen six months after an SMR, with a non-significant treatment effect difference of 2.09 (–0.63;4.80) in favor of the control group. No differences were found in secondary outcomes. In total, 260 potential DRPs were identified (2.6 (±1.8) per patient), of which 62% led to drug therapy optimization. Conclusion: In the current setting, a community pharmacist-led SMR did not improve QoL in PD patients, nor improved other pre-specified outcomes. Show more

Keywords: Parkinson’s disease, quality of life, drug therapy, medication adherence, drug administration schedule, clinical trials, pharmacists

DOI: 10.3233/JPD-213021

Citation: Journal of Parkinson's Disease, vol. 12, no. 4, pp. 1295-1306, 2022

Authors: Kerkemeyer, Linda | Claus, Inga | Kutscher, Michelle | von Stülpnagel, Vanessa | zur Nieden, Pauline | PNM + steering committee | Huchtemann, Tessa | Warnecke, Tobias

Article Type: Research Article

Abstract: Background: To improve Parkinson’s disease (PD) care, interdisciplinary and patient-centered treatment is mandatory. A key problem in many healthcare systems is the limited and unspecific communication among different healthcare professionals. Optimal collaboration between various professionals involved is indispensable. Parkinson’s Network Münsterland + (PNM +) is an interdisciplinary network of medical and non-medical experts involved in the treatment of PD patients in Germany. Objective: The aim of this evaluation was to analyze the network structures of PNM+ as well as communication and collaboration between PNM + partners. Methods: A mixed methods approach was applied consisting of a social network analysis, a validated …questionnaire on team effectiveness and semi-structured interviews focusing on perceived barriers and supportive aspects of PNM + . Results: Quantitative and qualitative data suggested increased collaboration between professionals within PNM + . The reciprocity of connections was 0.522 in the network of professional contacts. Regular exchanges in terms of interdisciplinary panel meetings and working groups stimulated knowledge transfer, leading to greater specialization of general neurologists and therapists in PD. The progressive density of the network from 0.136 to 0.279 illustrates the growing cooperation of PNM + partners. Interviewed partners requested more patient-specific collaboration but expected this to happen as the network evolved. Overall, PNM + has already improved both diagnosis and therapy thanks to knowledge transfer. Structured treatment recommendations helped to improve communication between healthcare professionals. Conclusion: PNM+ stimulated exchange between different healthcare professionals involved in the treatment of PD patients. This overcomes specific barriers within Germany’s highly fragmented healthcare system, such as the lack of communication between these disciplines. Show more

Keywords: Parkinson’s disease, community care networks, interdisciplinary health team, interdisciplinary communication

DOI: 10.3233/JPD-213072

Citation: Journal of Parkinson's Disease, vol. 12, no. 4, pp. 1307-1317, 2022

Authors: Stang, Cole D. | Mullan, Aidan F. | Camerucci, Emanuele | Hajeb, Mania | Turcano, Pierpaolo | Martin, Peter | Mielke, Michelle M. | Josephs, Keith A. | Splett, Matthew | Abler, Victor | Boeve, Bradley F. | Bower, James H. | Savica, Rodolfo

Article Type: Research Article

Abstract: BACKGROUND: Parkinson’s disease (PD)-associated psychosis is a well-known non-motor complication, occurring years after diagnosis of PD. Incidence data vary across different studies highlighting a need for long-term observation and clinical definition. OBJECTIVE: To determine the incidence of psychosis in patients with PD and to investigate their survival in an incident cohort study from 1991–2010 in Olmsted County, MN. METHODS: We used the Rochester Epidemiology Project to define an incident-cohort study of parkinsonism (1991–2010) in Olmsted County, MN. A movement-disorder specialist reviewed the electronic medical records and applied diagnosis criteria to PD. Psychosis was diagnosed using of …NINDS/NIMH unified criteria. RESULTS: We identified 669 cases of parkinsonism; 297 patients were clinically diagnosed with PD. 114/297 (38.4%) patients had evidence of psychosis (60% male); the median onset age of psychosis was 79.4 years. The incidence of Parkinson’s disease psychosis (PDP) was 4.28/100 person-years. PDP patients had a 71% increased risk of death compared to PD patients. In PD patients without psychosis, men had 73.4% increased risk of death compared to women, whereas no significant sex difference was observed among PDP men vs. women. Of 114 patients diagnosed with psychosis, 59 were treated with antipsychotics. There was no significant difference in survival between treated and untreated patients. CONCLUSION: PDP increased the odds of death compared to PD patients. Men with PD without psychosis had greater odds of death compared to women; however, in PD with psychosis the odds of death were comparable among sexes. Lastly, treatment with anti-psychotics did not significantly affect survival. Show more

Keywords: Parkinsonism, psychosis, hallucinations, delirium, antipsychotics

DOI: 10.3233/JPD-213035

Citation: Journal of Parkinson's Disease, vol. 12, no. 4, pp. 1319-1327, 2022