Levodopa Equivalent Daily Dose Research Articles

Physical Activity Improves Anxiety and Apathy in Early Parkinson's Disease: A Longitudinal Follow-Up Study.

Objective: In a prospective study, we investigated the association between physical activity and various motor, non-motor outcomes, and quality of life in early Parkinson's disease (PD) participants in the PD Longitudinal Singapore Study.Background: Prospective studies that examined the association between physical activity and motor and non-motor domains in early PD are lacking.Methods: 121 PD participants were followed-up prospectively to evaluate the association of physical activity with various symptom domains. The Physical Activity Scale for the Elderly (PASE) was used to measure physical activity annually. PD-related symptoms were categorized by motor, non-motor, and quality of life measures. Multivariate regression with gain score analysis was performed to understand the association of baseline PASE scores with the change of each variable at 1-year follow-up.Results: Higher baseline PASE scores (greater activity) were associated with a younger age, lower MDS-UPDRS motor scores, a smaller levodopa equivalent daily dose, better attention and memory scores, and better QoL. Activity scores in early PD declined on follow-up. Multivariate analysis revealed higher baseline physical activity to be associated with decreased anxiety and apathy scores at 1-year follow-up, after adjusting for demographic variables and medications.Conclusion: We demonstrated that higher baseline physical activity was associated with improved anxiety and apathy symptoms in early PD over a 1-year period.

Postprandial Increase in Mesenteric Blood Flow is Attenuated in Parkinson's Disease: A Dynamic PC-MRI Study.

Background:Gastrointestinal dysfunction and related clinical symptoms are common in Parkinson’s disease (PD), but the underlying mechanisms are still poorly understood.Objective:In this study, we investigated how PD affects the postprandial vascular response in the splanchnic circulation.Methods:23 patients with PD in the “ON-medication” state and 23 age- and sex-matched healthy control participants underwent serial phase-contrast magnetic resonance imaging (PC-MRI) to measure the postprandial blood flow response in the superior mesenteric artery (SMA). Participants ingested a standardized liquid test meal (∼400 kcal) and underwent four PC-MRI runs within the following hour. Each PC-MRI run consisted of six consecutive measurements of SMA blood flow.Results:In both groups, standardized food intake triggered an increase of blood flow in the SMA, but absolute and relative increases in blood flow were attenuated in patients compared to the control group (p < 0.001). While baseline blood flow in the SMA was comparable in both groups, the postprandial maximum blood flow was attenuated in patients (p = 0.03). The temporal dynamics of the postprandial blood flow did not differ between groups. Postprandial SMA blood flow increase in patients correlated neither with subjective reports of non-motor symptoms or upper gastrointestinal complaints, nor with levodopa equivalent daily dose or disease duration. Blood glucose measurements in between the PC-MRI runs showed a smaller postprandial increase in blood glucose in the patient group (p = 0.006).Conclusion:This study provides first-time evidence that patients with PD have an attenuated postprandial blood flow response in the SMA, indicating an impaired functional regulation of gastrointestinal perfusion in response to food intake in PD.

Electrode Fixation with Bone Cement or Stimloc® in Deep Brain Stimulation Surgery: A Comparative Study.

To examine the postoperative outcomes of electrode fixation using bone cement and Stimloc® in patients with Parkinson?s disease (PD) who underwent subthalamic nucleus (STN) deep brain stimulation (DBS). Between 2016 and 2018, permanent electrode fixation was performed in 30 patients with PD, of which 15 received bone cement and the remaining 15 received Stimloc®. Data regarding preoperative Unified Parkinson?s Disease Rating Scale (UPDRS) III scores, levodopa equivalent daily dose (LEDD) values, surgery duration, and the fixation technique used were recorded. Brain computed tomography was performed for early postoperative evaluation of pneumocephalus and possible hematoma as well as for the determination of migration 1 year postoperatively. UPDRS III scores and LEDD values were re-evaluated 1 year postoperatively; surgery duration, clinical effectiveness, and complication rates were compared between the two fixation techniques. A statistically significant difference in application time was observed between the two techniques (bone cement: 21 min, Stimloc®: 6 min). After 1 year from surgery, 0.92- and 0.88-mm migrations were observed in the bone cement and Stimloc® groups, respectively. A significant correlation between migration and the pneumocephalus volume was observed in both groups. No differences were observed between the groups regarding infection, migration, pneumocephalus volume, wound erosion, and clinical outcomes. Stimloc® is preferred over bone cement for electrode fixation in DBS surgeries as it is associated with shorter application duration; this increases patient comfort and tolerance during awake surgery. Clinical efficacy and complication rates associated with both techniques are similar.

Potential protective role of ACE-inhibitors and AT1 receptor blockers against levodopa-induced dyskinesias: a retrospective case-control study.

Growing evidence has highlighted that angiotensin-converting enzyme (ACE)-inhibitors (ACEi)/AT1 receptor blockers (ARBs) may influence the complex interplay between dopamine and the renin-angiotensin system in the nigrostriatal pathway, thus affecting the development of levodopa-induced dyskinesia in Parkinson's disease (PD). In the present study, we analyzed whether the use of this class of medication was associated with a reduced occurrence of levodopa-induced dyskinesia, using electronically-stored information of idiopathic PD patients enrolled at Novara University Hospital “Maggiore della Carità". We conducted a retrospective case-control study identifying PD patients with dyskinesias (PwD; n = 47) as cases. For each PwD we selected a non-dyskinetic control (NoD), nearly perfectly matched according to sex, Unified Parkinson's Disease Rating Scale (UPDRS) part III score, and duration of antiparkinsonian treatment. Binary logistic regression was used to evaluate whether dyskinesias were associated with ACEi/ARBs use. Ninety-four PD patients were included, aged 72.18 ± 9 years, with an average disease duration of 10.20 ± 4.8 years and 9.04 ± 4.9 years of antiparkinsonian treatment. The mean UPDRS part III score was 18.87 ± 7.6 and the median HY stage was 2. In the NoD group, 25 (53.2%) were users and 22 (46.8%) non-users of ACEi/ARBs. Conversely, in the PwD group, 11 (23.4%) were users and 36 non-users (76.6%) of this drug class (Pearson chi-square = 8.824, P = 0.003). Concerning general medication, there were no other statistically significant differences between groups. After controlling for tremor dominant phenotype, levodopa equivalent daily dose, HY 3-4, and disease duration, ACEi/ARBs use was a significant predictor of a lower occurrence of dyskinesia (OR = 0.226, 95% CI: 0.080–0.636, P = 0.005). Therefore, our study suggests that ACEi/ARBs may reduce levodopa-induced dyskinesia occurrence and, thanks to good tolerability and easy management, represent a feasible choice when dealing with the treatment of hypertension in PD patients. The study was approved by the Ethics Committee of Novara University Hospital “Maggiore della Carità” (CE 65/16) on July 27, 2016.

Falls Predict Acute Hospitalization in Parkinson's Disease.

There is a need for identifying risk factors for hospitalization in Parkinson's disease (PD) and also interventions to reduce acute hospital admission. To analyze the frequency, causes, and predictors of acute hospitalization (AH) in PD patients from a Spanish cohort. PD patients recruited from 35 centers of Spain from the COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015) cohort from January 2016 to November 2017, were included in the study. In order to identify predictors of AH, Kaplan-Meier estimates of factors considered as potential predictors were obtained and Cox regression performed on time to hospital encounter 1-year after the baseline visit. Thirty-five out of 605 (5.8%) PD patients (62.5±8.9 years old; 59.8% males) presented an AH during the 1-year follow-up after the baseline visit. Traumatic falls represented the most frequent cause of admission, being 23.7% of all acute hospitalizations. To suffer from motor fluctuations (HR [hazard ratio] 2.461; 95% CI, 1.065-5.678; p = 0.035), a very severe non-motor symptoms burden (HR [hazard ratio] 2.828; 95% CI, 1.319-6.063; p = 0.008), falls (HR 3.966; 95% CI 1.757-8.470; p = 0.001), and dysphagia (HR 2.356; 95% CI 1.124-4.941; p = 0.023) was associated with AH after adjustment to age, gender, disease duration, levodopa equivalent daily dose, total number of non-antiparkinsonian drugs, and UPDRS-IIIOFF. Of the previous variables, only falls (HR 2.998; 95% CI 1.080-8.322; p = 0.035) was an independent predictor of AH. Falls is an independent predictor of AH in PD patients.

Clinical Outcome of "Asleep" Deep Brain Stimulation for Parkinson Disease Using Robot-Assisted Delivery and Anatomic Targeting of the Subthalamic Nucleus: A Series of 152 Patients.

Recent advances in methods used for deep brain stimulation (DBS) include subthalamic nucleus electrode implantation in the "asleep" patient without the traditional use of microelectrode recordings or intraoperative test stimulation. To examine the clinical outcome of patients who have undergone "asleep" DBS for the treatment of Parkinson disease using robot-assisted electrode delivery. This is a retrospective review of clinical outcomes of 152 consecutive patients. Their outcomes at 1 yr postimplantation are reported; these include Unified Parkinson's Disease Rating Scale (UPDRS) assessment, Tinetti Mobility Test, Parkinson's Disease Questionnaire (PDQ)-39 quality of life assessment, Mattis Dementia Rating Scale, Beck Depression Inventory, and Beck Anxiety. We also report on a new parietal trajectory for electrode implantation. A total of 152 patients underwent assessment at 1 yr. UPDRS III improved from 39 to 20.5 (47%, P<.001). The total UPDRS score improved from 67.6 to 36.4 (46%, P<.001). UPDRS II scores improved from 18.9 to 10.5 (44%, P<.001) and UPDRS IV scores improved from 7.1 to 3.6 (49%, P<.001). There was a significant reduction in levodopa equivalent daily dose after surgery (mean: 35%, P<.001). PDQ-39 summary index improved by a mean of 7.1 points. There was no significant difference found in clinical outcomes between the frontal and parietal approaches. "Asleep" robot-assisted DBS of the subthalamic nucleus demonstrates comparable outcomes with traditional techniques in the treatment of Parkinson disease.

Predictors of Pain Severity and its Impact on Quality of Life in Patients with Parkinson's Disease.

Pain is a common and distressing symptom of Parkinson's disease (PD). The relation of pain, its predictors, and its impact on quality of life (QoL) in PD has not been studied in Indian PD patients. To assess the predictors of pain and investigate its impact on QoL among Indian PD patients. We conducted a cross-sectional study on 100 PD patients. The cases were diagnosed according to the UK brain bank criteria. Unified PD Rating Scale (UPDRS) parts III, V, and VI were employed to assess the severity of the disease. King's Parkinson Disease Pain Scale (KPPS) and PD questionnaire-8 (PDQ-8) were used to evaluate pain and QoL, respectively. Prevalence of different pain types in patients with PD was 70%, mainly including musculoskeletal (53%), fluctuation-related (35%), and nocturnal pain (27%). Subjects with pain developed PD symptoms at a younger age and had a longer duration of the disease. A positive correlation was found between KPPS scores and UPDRS parts III and V, while a negative correlation was observed with UPDRS part VI. Pain in PD subjects had a significant impact on the QoL. Most of the PD patients suffered some form of pain with significant correlations with motor disability and poor QoL. Predictors of pain severity among PD patients included a longer disease duration, younger age of disease onset, and a higher levodopa equivalent daily dose (LEDD).

Spinal Surgery after Bilateral Subthalamic Stimulation for Patients with Parkinson's Disease: A Retrospective Outcome Analysis of Pain and Functional Control.

Parkinson’s disease (PD) patients often suffer from spinal diseases requiring surgeries, although the risk of complications is high. There are few reports on outcomes after spinal surgery for PD patients with deep brain stimulation (DBS). The objective of this study was to explore the data on spinal surgery for PD patients with precedent DBS. We evaluated 24 consecutive PD patients with 28 spinal surgeries from 2007 to 2017 who received at least a 2-year follow-up. The characteristics and outcomes of PD patients after spinal surgery were compared to those of 156 non-PD patients with degenerative spinal diseases treated in 2013–2017. Then, the characteristics, outcomes, and spinal alignment of PD patients receiving DBS were analyzed in degenerative spinal/lumbar diseases. The mean age at the time of spinal surgery was 68 years. The Hoehn and Yahr score regarding PD was stage 1 for 8 patients, stage 2 for 2 patients, stage 3 for 8 patients, stage 4 for 10 patients, and stage 5 for 0 patient. The median preoperative L-DOPA equivalent daily dose was 410 mg. Thirteen patients (46%) received precedent subthalamic nucleus (STN) DBS. Lumbar lesions with pain were common, and operation and anesthesia times were long in PD patients. Pain and functional improvement of PD patients persisted for 2 years after surgery with a higher complication rate than for non-PD patients. PD patients with STN DBS maintained better lumbar lordosis for 2 years after spinal surgery. STN DBS significantly maintained spinal alignment with subsequent pain and functional amelioration 2 years after surgery. The outcomes of spinal surgery for PD patients might be favorably affected by thorough treatment for PD including DBS.

Fatigue correlates with sleep disturbances in Parkinson disease

Background:Many Parkinson disease (PD) patients complain about chronic fatigue and sleep disturbances during the night. The objective of this study is to determine the relationship between fatigue and sleep disturbances by using polysomnography (PSG) in PD patients.Methods:Two hundred and thirty-two PD patients (152 with mild fatigue and 80 with severe fatigue) were recruited in this study. Demographic information and clinical symptoms were collected. Fatigue severity scale (FSS) was applied to evaluate the severity of fatigue, and PSG was conducted in all PD patients. FSS ≥4 was defined as severe fatigue, and FSS <4 was defined as mild fatigue. Multivariate logistic regression and linear regression models were used to investigate the associations between fatigue and sleep disturbances.Results:Patients with severe fatigue tended to have a longer duration of disease, higher Unified Parkinson Disease Rating Scale score, more advanced Hoehn and Yahr stage, higher daily levodopa equivalent dose, worse depression, anxiety, and higher daytime sleepiness score. In addition, they had lower percentage of rapid eye movement (REM) sleep (P = 0.009) and were more likely to have REM sleep behavior disorder (RBD) (P = 0.018). Multivariate logistic regression analyses found that the presence of RBD and proportion of REM sleep were the independent predictors for fatigue. After the adjustment of age, sex, duration, body mass index, severity of disease, scores of Hamilton Rating Scale for Depression, Hamilton Anxiety Rating Scale, and other sleep disorders, proportion of REM sleep and degree of REM sleep without atonia in patients with PD were still associated with FSS score.Conclusion:Considering the association between fatigue, RBD, and the altered sleep architecture, fatigue is a special subtype in PD and more studies should be focused on this debilitating symptom.

A long-term follow-up of safety and clinical efficacy of NTCELL® [Immunoprotected (Alginate-encapsulated) porcine choroid plexus cells for xenotransplantation] in patients with Parkinson's disease

IntroductionIn 2019, we published the results of a Phase IIb randomized controlled trial of putaminal encapsulated porcine choroid plexus cell (termed NTCELL®) administration in patients with Parkinson's disease. This study failed to meet its primary efficacy end-point of a change in UPDRS part III score in the ‘off’ state at 26-weeks post-implant. However, a number of secondary end-points reached statistical significance. We questioned whether with longer follow-up, clinically significant improvements would be observed. For this reason, we decided to follow-up all patients periodically to week 104. Herein, we report the results of this long-term follow-up. MethodsAll 18 patients included in the original study were periodically re-assessed at weeks 52, 78 and 104 post-implant. At each time-point, motor and non-motor function, quality of life and levodopa equivalent daily dose was assessed using a standardized testing battery. ResultsAt week 104, no significant differences in UPDRS part III scores in the ‘off’ state were observed in any of the treatment groups compared to baseline. Only a single serious adverse event - hospitalisation due to Parkinson's disease rigidity not responding to changes in medications – was considered potentially related to the implant procedure. There was no evidence of xenogeneic viral transmission. ConclusionUn-blinded, long-duration follow-up to week 104 post-implantation showed no evidence that putaminal NTCELL® administration produces significant clinical benefit in patients with moderately advanced Parkinson's disease.

Risk factors for minor hallucinations in Parkinson's disease.

Minor hallucinations (MHs), including sense of presence, passage hallucinations, and visual illusions, have been reported in Parkinson's disease (PD). Here, we investigated the prevalence and associated risk factors for MHs according to appearance time. Data on the clinical characteristics and the appearance time of MHs for 100 PD patients were collected using a questionnaire and analyzed. MHs were classified into two groups according to the time when MHs appeared: MHs appearing while awake during the daytime (dMHs) and MHs appearing at arousal from sleep during the night or early morning (aMHs). Thirty-eight patients (38%) experienced MHs. dMHs and aMHs were present in 21 (21%) and 28 patients (28%), respectively. Compared to patients without MHs, patients with dMHs had more severe motor symptoms, longer disease duration, higher levodopa equivalent daily dose (LEDD), and higher rates of cognitive impairment and visual hallucinations during the daytime, whereas patients with aMHs had a higher rate of rapid eye movement sleep behavior disorder (RBD), longer disease duration, higher LEDD, and higher dopamine agonist dosage. Logistic regression analysis showed that cognitive impairment was significantly associated with dMHs (odds ratio (OR) 7.292, p=.001), and that RBD (OR 8.306, p<.001) and LEDD (OR 1.002, p=.049) were significantly associated with aMHs. Patients with MHs have different clinical characteristics according to the time when MHs appear. These findings have important clinical and prognostic implications and suggest appropriate therapeutic options for psychotic symptoms.

Aberrant Amplitude of Low-Frequency Fluctuations in Different Frequency Bands in Patients With Parkinson's Disease.

Previous studies reported abnormal spontaneous neural activity in Parkinson’s disease (PD) patients using resting-state functional magnetic resonance imaging (R-fMRI). However, the frequency-dependent neural activity in PD is largely unknown. Here, 35 PD patients and 35 age- and education-matched healthy controls (HCs) underwent R-fMRI scanning to investigate abnormal spontaneous neural activity of PD using the amplitude of low-frequency fluctuation (ALFF) approach within the conventional band (typical band: 0.01–0.08 Hz) and specific frequency bands (slow-5: 0.010–0.027 Hz and slow-4: 0.027–0.073 Hz). Compared with HCs, PD patients exhibited increased ALFF in the parieto-temporo-occipital regions, such as the bilateral inferior temporal gyrus/fusiform gyrus (ITG/FG) and left angular gyrus/posterior middle temporal gyrus (AG/pMTG), and displayed decreased ALFF in the left cerebellum, right precuneus, and left postcentral gyrus/supramarginal gyrus (PostC/SMG) in the typical band. PD patients showed greater increased ALFF in the left caudate/putamen, left anterior cingulate cortex/medial superior frontal gyrus (ACC/mSFG), left middle cingulate cortex (MCC), right ITG, and left hippocampus, along with greater decreased ALFF in the left pallidum in the slow-5 band, whereas greater increased ALFF in the left ITG/FG/hippocampus accompanied by greater decreased ALFF in the precentral gyrus/PostC was found in the slow-4 band (uncorrected). Additionally, the left caudate/putamen was positively correlated with levodopa equivalent daily dose (LEDD), Hoehn and Yahr (HY) stage, and disease duration. Our results suggest that PD is related to widespread abnormal brain activities and that the abnormalities of ALFF in PD are associated with specific frequency bands. Future studies should take frequency band effects into account when examining spontaneous neural activity in PD.

Visual hallucinations in Parkinson\u2019s disease are associated with thinning of the inner retina

Visual hallucinations (VH) are common in patients with Parkinson’s disease (PD), yet the underlying pathophysiological mechanisms are still unclear. We aimed to explore the association of the presence of VH with inner retinal thinning and, secondarily, with visual acuity. To this end, we included 40 PD patients in this exploratory study, of whom 14 had VH, and 22 age- and sex-matched healthy controls. All participants were interviewed for the presence of VH by a neurologist specialized in movement disorders and underwent a thorough ophthalmologic examination, including measurement of the best-corrected visual acuity (BCVA) and optical coherence tomography to obtain macular scans of the combined ganglion cell layer and inner plexiform layer (GCL-IPL). Patients with VH had a thinner GCL-IPL than patients without VH, which persisted after correction for age, disease stage, levodopa equivalent daily dose (LED) and cognitive function. Furthermore, BCVA was lower in the PD group with VH than in the PD group without VH, although only a trend remained after correction for age, disease stage, LED and cognitive function. Taken together, in patients with PD, visual hallucinations appear to be associated with a thinning of the inner retinal layers and, possibly, with reduced visual acuity. Further research using a longitudinal design is necessary to confirm these findings and to establish the causality of these relationships.

Enhancement of Executive Functions but Not Memory by Multidomain Group Cognitive Training in Patients with Parkinson's Disease and Mild Cognitive Impairment: A Multicenter Randomized Controlled Trial.

Background Meta-analyses have demonstrated cognitive training (CT) benefits in Parkinson's disease (PD) patients. However, the patients' cognitive status has only rarely been based on established criteria. Also, prediction analyses of CT success have only sparsely been conducted. Objective To determine CT effects in PD patients with mild cognitive impairment (PD-MCI) on cognitive and noncognitive outcomes compared to an active control group (CG) and to analyze CT success predictors. Methods Sixty-four PD-MCI patients (age: 67.61 ± 7.70; UPDRS-III: 26.58 ± 13.54; MoCA: 24.47 ± 2.78) were randomized to either a CT group or a low-intensity physical activity CG for six weeks (twice weekly, 90 minutes). Outcomes were assessed before and after training. MANOVAs with follow-up ANOVAs and multiple regression analyses were computed. Results Both interventions were highly feasible (participation, motivation, and evaluation); the overall dropout rate was 4.7%. Time × group interaction effects favoring CT were observed for phonemic fluency as a specific executive test (p=0.018, ηp2=0.092) and a statistical trend for overall executive functions (p=0.095, ηp2=0.132). A statistical trend for a time × group interaction effect favoring CG was shown for the digit span backward as a working memory test (p=0.098, ηp2=0.043). Regression analyses revealed cognitive baseline levels, education, levodopa equivalent daily dose, motor scores, and ApoE status as significant predictors for CT success. Conclusions CT is a safe and feasible therapy option in PD-MCI, yielding executive functions improvement. Data indicate that vulnerable individuals may show the largest cognitive gains. Longitudinal studies are required to determine whether CT may also attenuate cognitive decline in the long term. This trial is registered with DRKS00010186.

Association of sleep disturbance and freezing of gait in Parkinson disease: prevention/delay implications.

Freezing of gait (FOG) severely impairs life quality of Parkinson disease (PD) patients. The relationship between sleep disturbance and FOG in PD remains unclear, so in this study, we aimed to investigate that relationship. First, we assessed clinical characteristics of freezers and nonfreezers among PD patients. Next, we assessed clinical characteristics of PD patients with different PDSS1 scores (score on first item of Parkinson's Disease Sleep Scale). Finally, we prospectively followed a cohort of nonfreezers from a baseline clinical visit and to a maximum of 18 months and performed a Cox regression analysis to further investigate the relationship between PDSS1 score and FOG in PD. A total of 163 participants with PD were included in the baseline analysis. The freezers had significantly worse sleep compared with the nonfreezers. The proportion of freezers in the patients with low PDSS1 score (PDSS1 < 6) was significantly higher than that in the patients with high PDSS1 score (PDSS1 ≥ 6). A total of 52 nonfreezers were prospectively followed. During a maximum 18-month follow-up, FOG incidence (73%) in the PDSS1 < 6 group was significantly higher than that (24%) in the PDSS1 ≥ 6 group (P = .008). Low PDSS1 score (hazard ratio = 4.23, 95% CI 1.64-10.92, P = .003) and high levodopa equivalent daily dose (hazard ratio = 4.18, 95% CI 1.62-10.75, P = .003) were significantly associated with an increased hazard of FOG. Our study indicated that low PDSS1 score may be a risk indicator for the development of FOG and provided important insights into potential targets for the prevention/delay of FOG in PD.

Cohort Study in Parkinsonism: Delayed Transit, Accelerated Gastric Emptying, and Prodromal Dysmotility.

To evaluate gastric emptying (GE) and colonic transit in a cohort of patients with Parkinson disease and other parkinsonism disorders and to determine whether abnormal gut transit precedes motor onset of parkinsonism. Medical record review of 84 patients with parkinsonism who underwent clinically indicated transit studies at Mayo Clinic (2001-2019) and 11 patients with transit studies who subsequently developed parkinsonism. Data are summarized as median (interquartile range). The 84 patients (52% female) with parkinsonism were aged 72 (66-76) years with a disease duration of 5 (2-8) years: Parkinson disease = 70, multiple system atrophy = 7, dementia with Lewy bodies = 4, progressive supranuclear palsy = 2, and parkinsonian syndrome = 1. Ten had delayed GE, 10 slow colonic transit, 16 accelerated GE (14 Parkinson disease, 1 multiple system atrophy, and 1 parkinsonian syndrome), and 49 normal transit. One patient with parkinsonian syndrome had both slow colonic and accelerated gastric transit. Longer disease duration and higher levodopa equivalent daily dose were observed for Parkinson disease compared with other parkinsonisms and with slow compared with normal colonic transit. Of 11 patients (5 female) with transit studies who later developed motor parkinsonism after 4 (3-5) years, 1 had accelerated GE, 1 had delayed GE, and 1 had both delayed GE and colonic transit. Accelerated GE was newly identified in patients with parkinsonism, in addition to delayed GE or colonic transit. Furthermore, gut dysmotility was objectively identified to precede the motor onset of parkinsonism.

Effects of subthalamic nucleus deep brain stimulation on neuronal spiking activity in the substantia nigra pars compacta in a rat model of Parkinson’s disease

Parkinson’s Disease (PD) patients undergoing subthalamic nucleus deep brain stimulation (STN-DBS) therapy can reduce levodopa equivalent daily dose (LEDD) by approximately 50 %, leading to less symptoms of dyskinesia. The underlying mechanisms contributing to this reduction remain unclear, but studies posit that STN-DBS may increase striatal dopamine levels by exciting remaining dopaminergic cells in the substantia nigra pars compacta (SNc). Yet, no direct evidence has shown how SNc neuronal activity responds during STN-DBS in PD. Here, we use a hemiparkinsonian rat model of PD and employ in vivo electrophysiology to examine the effects of STN-DBS on SNc neuronal spiking activity. We found that 43 % of SNc neurons in naïve rats reduced their spiking frequency to 29.8 ± 18.5 % of baseline (p = 0.010). In hemiparkinsonian rats, a higher number of SNc neurons (88 % of recorded cells) decreased spiking frequency to 61.6 ± 4.4 % of baseline (p = 0.030). We also noted that 43 % of SNc neurons in naïve rats increased spiking frequency from 0.2 ± 0.0 Hz at baseline to 1.8 ± 0.3 Hz during stimulation, but only 1 SNc neuron from 1 hemiparkinsonian rat increased its spiking frequency by 12 % during STN-DBS. Overall, STN-DBS decreased spike frequency in the majority of recorded SNc neurons in a rat model of PD. Less homogenous responsiveness in directionality in SNc neurons during STN-DBS was seen in naive rats. Plausibly, poly-synaptic network signaling from STN-DBS may underlie these changes in SNc spike frequencies.

Association Between Nonmotor Symptoms and Nonadherence to Medication in Parkinson's Disease

Background: Nonadherence to medication is a common and serious issue in the treatment of patients with Parkinson's disease (PD). Among others, distinct nonmotor symptoms (NMS) were found to be associated with nonadherence in PD. Here, we aimed to confirm the association between NMS and adherence.Methods: In this observational study, the following data were collected: sociodemographic data, the German versions of the Movement Disorder Society-sponsored revision of the unified Parkinson's disease rating scale for motor function (MDS-UPDRS III), Hoehn and Yahr (H&Y) stage, levodopa equivalent daily dose (LEDD), Becks depression inventory II (BDI-II), nonmotor symptoms questionnaire (NMSQ), and the Stendal adherence to medication score (SAMS).Results: The final sample included 137 people with PD [54 (39.4%) females] with a mean age of 71.3 ± 8.2 years. According to SAMS, 10.9% of the patients were fully adherent, 73% were moderately nonadherent, and 16.1% showed clinically significant nonadherence. Nonadherence was associated with LEDD, BDI-II, education level, MDS-UPDRS III, and the NMSQ. The number of NMS was higher in nonadherent patients than in adherent patients. In the multiple stepwise regression analysis, the items 5 (constipation), 17 (anxiety), and 21 (falls) predicted nonadherence to medication. These NMSQ items also remained significant predictors for SAMS after correction for LEDD, MDS-UPDRS III, BDI-II, age, education level, gender, and disease duration.Conclusion: Our study, in principle, confirms the association between NMS burden and nonadherence in PD. However, in contrast to other clinical factors, the relevance of NMSQ in terms of nonadherence is low. More studies with larger sample sizes are necessary to explore the impact of distinct NMS on adherence.

Mobile Application for Parkinson's Disease Deep Brain Stimulation (MAP DBS): An Open-Label, Multicenter, Randomized, Controlled Clinical Trial

Mobile Application for Parkinson's Disease Deep Brain Stimulation (MAP DBS): An Open-Label, Multicenter, Randomized, Controlled Clinical Trial

Intraoperative Neurophysiologic Assessment in Deep Brain Stimulation Surgery and its Impact on Lead Placement.

While the efficacy of deep brain stimulation (DBS) to treat various neurological disorders is undisputed, the surgical methods differ widely and the importance of intraoperative microelectrode recording (MER) or macrostimulation (MS) remains controversially debated. The objective of this study is to evaluate the impact of MER and MS on intraoperative lead placement. We included 101 patients who underwent awake bilateral implantation of electrodes in the subthalamic nucleus with MER and MS for Parkinson's disease from 2009 to 2017 in a retrospective observational study. We analyzed intraoperative motor outcomes between anatomically planned stimulation point (PSP) and definite stimulation point (DSP), lead adjustments and Unified Parkinson's Disease Rating Scale Item III (UPDRS-III), levodopa equivalent daily dose (LEDD), and adverse events (AE) after 6 months. We adjusted 65/202 leads in 47/101 patients. In adjusted leads, MS results improved significantly when comparing PSP and DSP (p < 0.001), resulting in a number needed to treat of 9.6. After DBS, UPDRS-III and LEDD improved significantly after 6 months in adjusted and nonadjusted patients (p < 0.001). In 87% of leads, the active contact at 6 months still covered the optimal stimulation point during surgery. In total, 15 AE occurred. MER and MS have a relevant impact on the intraoperative decision of final lead placement and prevent from a substantial rate of poor stimulation outcome. The optimal stimulation points during surgery and chronic stimulation strongly overlap. Follow-up UPDRS-III results, LEDD reductions, and DBS-related AE correspond well to previously published data.