Levodopa Equivalent Dose Research Articles

Central retinal microvasculature damage is associated with orthostatic hypotension in Parkinson’s disease

Orthostatic hypotension (OH) is a common non-motor symptom in Parkinson’s disease (PD). OH can cause cerebral and retinal hypoperfusion and is associated with microvascular damage in PD. Optical coherence tomography angiography (OCTA) is a non-invasive technology that can be used to visualize the retinal microvasculature and detect microvascular damage in PD. In the present study, 51 PD patients (OH+, n = 20, 37 eyes; OH−, n = 32, 61 eyes) and 51 healthy controls (100 eyes) were evaluated. The Unified Parkinson’s Disease Rating Scale III, Hoehn and Yahr scale, Montreal Cognitive Assessment, levodopa equivalent daily dose, and vascular risk factors, including hypertension, diabetes, and dyslipidemia, were investigated. PD patients underwent a head-up tilt (HUT) test. The PD patients had a lower superficial retinal capillary plexus (SRCP) density in the central region than control patients. The PDOH+ group had lower vessel density in the SRCP of the central region compared with the control group and lower vessel density in the DRCP of the central region than the PDOH− and control groups. The changes in systolic and diastolic blood pressure during the HUT test in PD patients showed a negative correlation with the vessel density in the DRCP central region. The presence of OH was a critical factor associated with central microvasculature damage in PD. These findings indicate that OCTA can be a useful and non-invasive tool for detecting microvasculature damage in PD patients.

Timely referral for device-aided therapy in Parkinson's disease. Development of a screening tool

BackgroundTimely referral of Parkinson's disease (PD) patients to specialized centers for treatment with device-aided therapies (DAT) is suboptimal. ObjectiveTo develop a screening tool for timely referral for DAT in PD and to compare the tool with the published 5-2-1 criteria. MethodsA cross-sectional, observational study was performed in 8 hospitals in the catchment area of a specialized movement disorder center in the Northern part of the Netherlands. The target population comprised PD patients not yet on DAT visiting the outpatient clinic of participating hospitals. The primary outcome was apparent eligibility for referral for DAT based on consensus by a panel of 5 experts in the field of DAT. Multivariable logistic regression modelling was used to develop a screening tool for eligibility for referral for DAT. Potential predictors were patient and disease characteristics as observed by attending neurologists. ResultsIn total, 259 consecutive PD patients were included, of whom 17 were deemed eligible for referral for DAT (point prevalence: 6.6%). Presence of response fluctuations and troublesome dyskinesias were the strongest independent predictors of being considered eligible. Both variables were included in the final model, as well as levodopa equivalent daily dose. Decision curve analysis revealed the new model outperforms the 5-2-1 criteria. A simple chart was constructed to provide guidance for referral. Discrimination of this simplified scoring system proved excellent (AUC after bootstrapping: 0.97). ConclusionsAwaiting external validation, the developed screening tool already appears promising for timely referral and subsequent treatment with DAT in patients with PD.

Morbidity Milestones Demonstrate Long Disability-Free Survival in Parkinson's Disease Patients with Deep Brain Stimulation of the Subthalamic Nucleus.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD). The long-term benefit in PD patients with STN-DBS in comparison to medical treatment (MT) alone has not yet been demonstrated conclusively. To judge the long-term outcome of patients with STN-DBS. To assess the evolution of PD symptoms and health-related quality of life (HRQoL) after deep brain stimulation (DBS) surgery, we conducted a cross-sectional analysis of 115 patients with STN-DBS with rater-based scales and self-reported questionnaires. In addition, we screened records of all our STN-DBS patients (2001-2019, n=162 patients) for the onset of the morbidity milestones (falls, hallucinations, dementia, and nursing home placement) to assess disability-free life expectancy. In the first year of STN-DBS, levodopa equivalent dose was reduced and motor function improved. Nonmotor symptoms and cognition remained stable. These effects were similar to previous studies. Morbidity milestones occurred 13 ± 7 years after diagnosis. Motor function, cognition, and HRQoL significantly worsened after the occurrence of any milestone, confirming the clinical relevance of these milestones. After onset of the first milestone, mean survival time was limited to 5 ± 0.8 years, which is comparable with patients with PD but without STN-DBS. On average, PD patients with STN-DBS live with their disease for a longer time, and morbidity milestones occur later in the disease course than in PD patients with MT. As judged by morbidity milestones, morbidity remains compressed into the final 5 years of life in PD patients with STN-DBS.

Effects of Dihydropyridines on the Motor and Cognitive Outcomes of Patients with Parkinson's Disease.

Dihydropyridines (DHPs) may have neuroprotective effects against Parkinson's disease (PD). This study investigated the effects of DHPs on nigrostriatal dopaminergic denervation and longitudinal motor and cognitive outcomes in PD. We classified 476 patients with drug-naive PD who had undergone dopamine transporter imaging into three groups. They were selected according to a prior diagnosis of hypertension and use of DHPs and were matched using propensity scores: patients without hypertension (HTN-; n=50) and patients with hypertension treated without DHP (HTN+/DHP-; n=50) or with DHP (HTN+/DHP+; n=50). Multiple linear regression and linear mixed model analyses were performed to determine intergroup differences in baseline dopamine transporter availability and longitudinal changes in the levodopa-equivalent dose, respectively. Using Kaplan-Meier analyses, we compared the risks of levodopa-induced dyskinesia, wearing off, and dementia-free survival during the 5.06 years of the mean follow-up period. The Cox regression model determined the independent effects of DHPs on dementia conversion. Dopamine transporter availability in all striatal subregions was comparable between the HTN-, HTN+/DHP-, and HTN+/DHP+ groups. The risks of levodopa-induced dyskinesia and wearing off, as well as longitudinal changes in the levodopa-equivalent dose, did not differ between the groups. The HTN+/DHP+ group had a lower risk of developing dementia than the HTN+/DHP- (Bonferroni-corrected Plog-rank =0.036) group. The use of DHP was independently associated with a lower risk of dementia conversion after controlling for other antihypertensive drugs and confounding factors (hazard ratio, 0.242; 95% confidence interval, 0.087-0.668; P=0.006). DHPs may be associated with better long-term cognitive outcomes in hypertensive patients with PD. © 2023 International Parkinson and Movement Disorder Society.

Levodopa Equivalent Dose of Safinamide: A Multicenter, Longitudinal, Case-Control Study.

Effects of dopaminergic medications used to treat Parkinson's disease (PD) may be compared with each other by using conversion factors, calculated as Levodopa equivalent dose (LED). However, current LED proposals on MAO-B inhibitors (iMAO-B) safinamide and rasagiline are still based on empirical approaches. To estimate LED of safinamide 50 and 100 mg. In this multicenter, longitudinal, case-control study, we retrospectively reviewed clinical charts of 500 consecutive PD patients with motor complications and treated with (i) safinamide 100 mg (N=130), safinamide 50 mg (N=144), or rasagiline 1 mg (N=97) for 9 ± 3 months and a control group of patients never treated with any iMAO-B (N=129). Major baseline features (age, sex, disease duration and stage, severity of motor signs and motor complications) were similar among the groups. Patients on rasagiline had lower UPDRS-II scores and Levodopa dose than control subjects. After a mean follow-up of 8.8-to-10.1 months, patients on Safinamide 50 mg and 100 mg had lower UPDRS-III and OFF-related UPDRS-IV scores than control subjects, who in turn had larger increase in total LED than the three iMAO-B groups. After adjusting for age, disease duration, duration of follow-up, baseline values and taking change in UPDRS-III scores into account (sensitivity analysis), safinamide 100 mg corresponded to 125 mg LED, whereas safinamide 50 mg and rasagiline 1mg equally corresponded to 100 mg LED. We used a rigorous approach to calculate LED of safinamide 50 and 100 mg. Large prospective pragmatic trials are needed to replicate our findings.

The effect of levodopa treatment on vascular endothelial function in Parkinson's disease.

There has been increasing awareness that micro-vascular alteration or vascular inflammation has been associated with levodopa-induced dyskinesia in PD. Vascular endothelial function assessed by flow mediated dilation (FMD) is known to reflect early microvascular change. We compare the impact of levodopa or dopamine agonist treatment on the change of FMD in de novo PD patients. This retrospective study used a selected sample from registry. We identified de-novo PD patients who underwent FMD at baseline, and follow-up FMD after 1year (± 2month) of levodopa (n = 18) or dopamine agonist (n = 18) treatment. FMD decreased after levodopa (8.60 ± 0.46 to 7.21 ± 0.4, p = 0.002) but there were no significant changes after DA treatment (8.33 ± 0.38 to 8.22 ± 0.33, p = 0.26). Homocysteine rose (11.52 ± 0.45 to 14.33 ± 0.68, p < 0.05) during levodopa treatment, but dopamine agonist had no effect (10.59 ± 0.38 to 11.38 ± 0.67, p = 0.184). Correlation analysis revealed that the changes in homocysteine level had non-significant correlation with FMD change (r = - 0.30, p = 0.06). FMD change was not associated with age (p = 0.47), disease duration (p = 0.81), baseline motor UPDRS (p = 0.43), motor UPDRS change (p = 0.64), levodopa equivalent dose change (p = 0.65). We found that 1-year levodopa treatment may adversely affect vascular endothelial function in de novo PD. Further studies are needed to clarify the exact pathogenesis and clinical implication of levodopa-induced endothelial dysfunction in PD.

Heath management app use in Parkinson’s disease and quality of life during the COVID-19 pandemic

BackgroundSocial distancing during the COVID-19 pandemic affected follow-up visits and medication availability for patients with Parkinson’s disease (PD). As a promising strategy to deal with these challenges, the implementation of health management smartphone apps was accelerated. However, whether more intense use of such apps could improve the quality of life (QoL) for PD patients during the COVID-19 pandemic was unknown.MethodsUsing a PD management app, this observational study assessed changes in QoL, as determined by PD Questionnaire 8 (PDQ-8), among PD patients before (Jan 20, 2019 to Oct 6, 2019) and after the beginning of the COVID-19 lockdown (Jan 20, 2020 to Oct 6, 2020). According to adherence to use of the app, participants were divided into low adherence, moderate adherence, and high adherence groups. A total of 4979 PD patients registered in the app, and 226 PD patients were enrolled, including 57 patients with low adherence, 112 with moderate adherence and 57 with high adherence. A generalized linear model was used to evaluate the change of PDQ-8 scores across these three different adherence groups.ResultsAfter the COVID-19 lockdown (1-year follow-up), the PDQ-8 scores are reduced by 0.8 (95% CI, 0.3–1.4) in all participants (P = 0.004). After adjustment for age, gender, education, disease duration and levodopa equivalent dose, PDQ-8 scores significantly less reduced in the high adherence group (0.3; 95% CI, 0.6–1.2) compared to the low adherence (1.9; 95% CI, 0.7–3.1) (P = 0.040) and moderate adherence groups (0.6; 95% CI, 0.2–1.3) (P = 0.012).ConclusionsA health management smartphone-based app might be a way to both measure and improve QoL among PD patients, provided that sufficient adherence is achieved.

Non-motor effects of deep brain stimulation in Parkinson's disease motor subtypes

IntroductionDeep brain stimulation (DBS) is a well-established treatment for patients with Parkinson's disease (PD) improving quality of life, motor, and non-motor symptoms. However, non-motor effects in PD subtypes are understudied. We hypothesized that patients with ‘postural instability and gait difficulty’ (PIGD) experience more beneficial non-motor effects than ‘tremor-dominant’ patients undergoing DBS for PD. MethodsIn this prospective, observational, international multicentre study with a 6-month follow-up, we assessed the Non-Motor Symptom Scale (NMSS) as primary and the following secondary outcomes: Unified PD Rating Scale-motor examination (UPDRS-III), Scales for Outcomes in PD (SCOPA)-activities of daily living (ADL) and -motor complications, PDQuestionnaire-8 (PDQ-8), and levodopa-equivalent daily dose (LEDD). We analysed within-group longitudinal changes with Wilcoxon signed-rank test and Benjamini-Hochberg correction for multiple comparisons. Additionally, we explored outcome between-group differences of motor subtypes with Mann-Whitney U-tests. ResultsIn 82 PIGD and 33 tremor-dominant patients included in this study, baseline NMSS total scores were worse in PIGD patients, both groups experienced postoperative improvements of the NMSS sleep/fatigue domain, and between-group differences in postoperative outcomes were favourable in the PIGD group for the NMSS total and miscellaneous domain scores. ConclusionsThis study provides evidence of a favourable outcome of total non-motor burden in PIGD compared to tremor-dominant patients undergoing DBS for PD. These differences of clinical efficacy on non-motor aspects should be considered when advising and monitoring patients with PD undergoing DBS.

Sex Differences in Motor and Non-Motor Symptoms among Spanish Patients with Parkinson's Disease.

Sex plays a role in Parkinson's disease (PD) mechanisms. We analyzed sex difference manifestations among Spanish patients with PD. PD patients who were recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. A cross-sectional and a two-year follow-up analysis were conducted. Univariate analyses and general linear model repeated measure were used. At baseline, data from 681 PD patients (mean age 62.54 ± 8.93) fit the criteria for analysis. Of them, 410 (60.2%) were males and 271 (39.8%) females. There were no differences between the groups in mean age (62.36 ± 8.73 vs. 62.8 ± 9.24; p = 0.297) or in the time from symptoms onset (5.66 ± 4.65 vs. 5.21 ± 4.11; p = 0.259). Symptoms such as depression (p < 0.0001), fatigue (p < 0.0001), and pain (p < 0.00001) were more frequent and/or severe in females, whereas other symptoms such as hypomimia (p < 0.0001), speech problems (p < 0.0001), rigidity (p < 0.0001), and hypersexuality (p < 0.0001) were more noted in males. Women received a lower levodopa equivalent daily dose (p = 0.002). Perception of quality of life was generally worse in females (PDQ-39, p = 0.002; EUROHIS-QOL8, p = 0.009). After the two-year follow-up, the NMS burden (Non-Motor Symptoms Scale total score) increased more significantly in males (p = 0.012) but the functional capacity (Schwab and England Activities of Daily Living Scale) was more impaired in females (p = 0.001). The present study demonstrates that there are important sex differences in PD. Long-term prospective comparative studies are needed.

Ambiental Factors in Parkinson’s Disease Progression: A Systematic Review

Background and Objectives: So far, there is little evidence of the ambient effect on motor and non-motor symptoms of Parkinson's Disease (PD). This systematic review aimed to determine the association between ambiental factors and the progression of PD. Materials and Methods: A systematic literature search of PubMed, Cochrane, Embase, and Web of Science was conducted up to 21 December 2021 according the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Eight articles were used in the analyses. Long-term exposure to fine particles (particulate matter ≤ 2.5 μm; PM2.5) was positively associated with disease aggravation in two studies. Short-term PM2.5 exposure was positively associated with disease aggravation in three studies. Significant associations were found between PD aggravation and NO2, SO2, CO, nitrate and organic matter (OM) concentrations in two studies. Associations were more pronounced, without reaching statistical significance however, in women, patients over 65 years old and cold temperatures. A 1% increase in temperature was associated with a significant 0.18% increase in Levodopa Equivalent Dose (LED). Ultraviolet light and humidity were not significantly associated with an increase in LED. There was no difference in hallucination severity with changing seasons. There was no evidence for seasonal fluctuation in Unified Parkinson's Disease Rating Scale (UPDRS) scores. Conclusions: There is a link between air pollutants and temperature for PD progression, but this has yet to be proven. More longitudinal studies are warranted to confirm these findings.

Identifying the therapeutic zone in globus pallidus deep brain stimulation for Parkinson's disease.

The globus pallidus internus (GPI) has been demonstrated to be an effective surgical target for deep brain stimulation (DBS) treatment in patients with medication-refractory Parkinson's disease (PD). The ability of neurosurgeons to define the area of greatest therapeutic benefit within the globus pallidus (GP) may improve clinical outcomes in these patients. The objective of this study was to determine the best DBS therapeutic implantation site within the GP for effective treatment in PD patients. The authors performed a retrospective review of 56 patients who underwent bilateral GP DBS implantation at their institution during the period from January 2015 to January 2020. Each implanted contact was anatomically localized. Patients were followed for stimulation programming for at least 6 months. The authors reviewed preoperative and 6-month postsurgery clinical outcomes based on data from the Unified Parkinson's Disease Rating Scale Part III (UPDRS III), dyskinesia scores, and levodopa equivalent daily dose (LEDD). Of the 112 leads implanted, the therapeutic cathode was most frequently located in the lamina between the GPI external segment (GPIe) and the GP externus (GPE) (n = 40). Other common locations included the GPE (n = 24), the GPIe (n = 15), and the lamina between the GPI internal segment (GPIi) and the GPIe (n = 14). In the majority of patients (73%) a monopolar programming configuration was used. At 6 months postsurgery, UPDRS III off medications (OFF) and on stimulation (ON) scores significantly improved (z = -4.02, p < 0.001), as did postsurgery dyskinesia ON scores (z = -4.08, p < 0.001) and postsurgery LEDD (z = -4.7, p < 0.001). Though the ventral GP (pallidotomy target) has been a commonly used target for GP DBS, a more dorsolateral target may be more effective for neuromodulation strategies. The assessment of therapeutic contact locations performed in this study showed that the lamina between GPI and GPE used in most patients is the optimal central stimulation target. This information should improve preoperative GP targeting.

Quantitative Transcranial Sonography Evaluation of Substantia Nigra Hyperechogenicity Is Useful for Predicting Levodopa-Induced Dyskinesia in Parkinson Disease.

Levodopa-induced dyskinesia (LID) is a common motor complication in Parkinson disease (PD). Abnormal substantia nigra hyperechogenicity (SN+), detected by transcranial sonography (TCS), plays an important role in the differential diagnosis of PD. The purpose of this study was to investigate the predictive performance of quantitative SN+ evaluations for LID. Five hundred sixty-two individuals were included in our analysis, and 198 individuals were followed up. These individuals were divided into two groups at baseline: the PD with LID (PD+LID) group and the PD without LID (PD-LID) group. The association between total hyperechogenic area of the SN on both sides (SNT) and LID was analyzed by binary logistic analysis. A binary logistic regression model including SNT was applied to establish a model for discriminating LID. At baseline, 105 (18.7%) individuals were diagnosed with LID. The PD+LID group had a longer disease duration, shorter education duration, higher levodopa equivalent doses, greater disease severity and larger SNT. A model combining clinical features and SNT was further established with better efficiency (area under the receiver operating characteristic curve=0.839). One hundred ninety-eight individuals were followed up; individuals with a larger SNT and a higher predicted probability were more likely to develop LID in our follow-up. Our study determined that quantitative TCS evaluation of SN echogenicity is useful in predicting LID in PD.

Extra-Basal Ganglia Brain Structures Are Related to Motor Reserve in Parkinson's Disease.

The "motor reserve" is an emerging concept based on the discrepancy between the severity of parkinsonism and dopaminergic degeneration; however, the related brain structures have not yet been elucidated. We investigated brain structures relevant to the motor reserve in Parkinson's disease (PD) in this study. Patients with drug-naïve, early PD were enrolled, who then underwent dopamine transporter (DAT) scan and diffusion tensor imaging (DTI). The severity of motor symptoms was evaluated with the Unified Parkinson's Disease Rating Scale score of bradykinesia and rigidity on the more affected side and dopaminergic degeneration of DAT uptake of the more affected putamen. Individual motor reserve estimate (MRE) was evaluated based on the discrepancy between the severity of motor symptoms and dopaminergic degeneration. Using DTI and the Brainnetome atlas, brain structures correlated with MRE were identified. We enrolled 193 patients with drug-naïve PD (mean disease duration of 15.6±13.2 months), and the MRE successfully predicted the increase of levodopa equivalent dose after two years. In the DTI analysis, fractional anisotropy values of medial, inferior frontal, and temporal lobes, limbic structures, nucleus accumbens, and thalamus were positively correlated with the MRE, while no brain structures were correlated with mean diffusivity. Additionally, degree centrality derived from the structural connectivity of the frontal and temporal lobes and limbic structures was positively correlated with the MRE. Our results show empirical evidence for MR in PD and brain structures relevant to MR, particularly, the extra-basal ganglia system including the limbic and frontal structures.

Tinetti balance performance is associated with mortality in older adults with late-onset Parkinson’s disease: a longitudinal study

BackgroundParkinson’s disease (PD) is associated with a 3-fold mortality risk, which is closely related to advancing age. Evidence is lacking regarding the factors associated with the risks of mortality or nursing-home (NH) admission, in elderly patients with PD. We aimed at identifying the clinical characteristics associated with these outcomes, in older community-dwelling patients with late-onset PD.MethodsRetrospective, observational analysis of data from geriatric day hospital patients. Motor assessment included Unified Parkinson Disease Rating Scale (UPDRS) part III score, Tinetti Performance Oriented Mobility Assessment (POMA) balance and gait tests, and gait speed. Levodopa equivalent dose, comorbidity, cognitive performance, Activities of Daily Living performance were examined. Cox proportional hazards models were performed to identify the factors associated with mortality and NH admission rate (maximum follow-up time = 5 years).ResultsWe included 98 patients, mean age 79.4 (SD = 5.3) of whom 18 (18.3%) died and 19 (19.4%) were admitted into NH, over a median follow-up of 4 years. In multivariate Cox models, poor balance on the Tinetti POMA scale (HR = 0.82 95%CI (0.66–0.96), p = .023) and older age (HR = 1.12 95%CI (1.01–1.25), p = .044) were the only variables significantly associated with increased mortality risk. A Tinetti balance score below 11/16 was associated with a 6.7 hazard for mortality (p = .006). No specific factor was associated with NH admissions.ConclusionsAge and the Tinetti POMA score were the only factors independently associated with mortality. The Tinetti POMA scale should be considered for balance assessment and as a screening tool for the most at-risk individuals, in this population.

Both Motor and Non-Motor Fluctuations Matter in the Clinical Management of Patients with Parkinson's Disease: An Exploratory Study.

Non-motor symptoms (NMS) characterize the Parkinson's disease (PD) clinical picture, and as well as motor fluctuations, PD patients can also experience NMS fluctuations (NMF). The aim of this observational study was to investigate the presence of NMS and NMF in patients with PD using the recently validated Non-Motor Fluctuation Assessment questionnaire (NoMoFa) and to evaluate their associations with disease characteristics and motor impairment. Patients with PD were consecutively recruited, and NMS, NMF, motor impairment, motor fluctuations, levodopa-equivalent daily dose, and motor performance were evaluated. One-third of the 25 patients included in the study (10 females, 15 males, mean age: 69.9 ± 10.3) showed NMF, and patients with NMF presented a higher number of NMS (p < 0.01). Static NMS and NoMoFa total score were positively associated with motor performance assessed with the Global Mobility Task (p < 0.01 and p < 0.001), and the latter was also correlated with motor impairment (p < 0.05) but not with motor fluctuations. Overall, this study shows evidence that NMF are frequently reported by mild-to-moderate PD patients and associated with an increased number of NMS. The relationship between NoMoFa total score and motor functioning highlights the importance of understanding the clinical role of NMS and NMF in the management of PD patients.

Are the EEG microstates correlated with motor and non-motor parameters in patients with Parkinson's disease?

ObjectivesThis study compared electroencephalography microstates (EEG-MS) of patients with Parkinson's disease (PD) to healthy controls and correlated EEG-MS with motor and non-motor aspects of PD. MethodsThis cross-sectional exploratory study was conducted with patients with PD (n = 10) and healthy controls (n = 10) matched by sex and age. We recorded EEG-MS using 32 channels during eyes‐closed and eyes‐open conditions and analyzed the four classic EEG-MS maps (A, B, C, D). Clinical information (e.g., disease duration, medications, levodopa equivalent daily dose), motor (Movement Disorder Society - Unified Parkinson Disease Rating Scale II and III, Timed Up and Go simple and dual-task, and Mini-Balance Evaluation Systems Test) and non-motor aspects (Mini-Mental State Exam [MMSE], verbal fluency, Hospital Anxiety and Depression Scale, and Parkinson's Disease Questionnaire-39 [PDQ-39]) were assessed in the PD group. Mann-Whitney U test was used to compare groups, and Spearman's correlation coefficient to analyze the correlations between coverage of EEG-MS and clinical aspects of PD. ResultsThe PD group showed a shorter duration of EEG-MS C in the eyes-closed condition than the control group. We observed correlations (rho = 0.64 to 0.82) between EEG-MS B, C, and D and non-motor aspects of PD (MMSE, verbal fluency, PDQ-39, and levodopa equivalent daily dose). ConclusionAlterations in EEG-MS and correlations between topographies and cognitive aspects, quality of life, and medication dose indicate that EEG could be used as a PD biomarker. Future studies should investigate these associations using a longitudinal design.

Assessing the risks of treatment in Parkinson disease psychosis: An in-depth analysis.

Parkinson disease (PD) psychosis (PDP) is a disabling non-motor symptom. Pharmacologic treatment is limited to pimavanserin, quetiapine, and clozapine, which do not worsen parkinsonism. A Food and Drug Administration black box warning exists for antipsychotics, suggesting increased mortality in elderly patients with dementia. However, the reasons for higher mortality are unknown. Expanding on prior work exploring mortality in treated PDP patients, we conducted a retrospective comparison to understand the links between treatment regimen, clinical characteristics, and negative outcomes. Electronic medical record data extraction included clinically diagnosed PD patients between 4/29/16-4/29/19 and excluded patients with primary psychiatric diagnoses or atypical parkinsonism. Mortality and clinical characteristics during the study period were compared between untreated patients and those receiving pimavanserin, quetiapine, or both agents (combination). Mortality analyses were adjusted for age, sex, levodopa equivalent daily dose (LEDD), and dementia. The pimavanserin group (n = 34) had lower mortality than the untreated group (n = 66) (odds ratio = 0.171, 95% confidence interval: 0.025-0.676, p = 0.026). The untreated group had similar mortality compared to the quetiapine (n = 147) and combination (n = 68) groups. All treated groups had a higher LEDD compared to the untreated group, but no other differences in demographics, hospitalizations, medical comorbidities, medications, or laboratory values were found between the untreated and treated groups. PDP patients receiving pimavanserin had lower mortality than untreated patients. We found no other clear differences in clinical characteristics to explain the mortality risk. Prospective randomized trials are needed to definitively identify the optimal PDP treatment regimen and associated risks.

Septum Pellucidum Cyst in Patient with Parkinson’s Disease-minimally Invasive Staged Therapy

Background: The aim of the case report is to present the minimally invasive staged treatment of a patient with motor complications of Parkinson’s disease with a large septum pellucidum cyst.&#x0D; Material and Method: A two-stage surgical strategy was proposed by the movement disorders team: neuroendoscopic cyst fenestration with subsequent implantation of deep brain stimulation electrodes (subthalamic nucleus) depending on the effect of neuroendoscopic treatment.&#x0D; Results: Despite the technical success of a neuroendoscopic cyst fenestration, as evidenced by a reduction in cyst volume, intraoperative ventriculocystography and postoperative CT showing free communication between the cyst and the ventricular system the motor symptoms caused by Parkinson’s disease remained unchanged. A bilateral subthalamic deep brain stimulation system was implanted with good functional results as documented by her UPRDS III score in the off-medication state (52 points preoperative and 34 point after 6 years postoperative) and reduction of L-DOPA equivalent dose (60% of the pre-deep brain stimulation level). &#x0D; Conclusion: Minimally invasive therapy-neuroendoscopic cyst fenestration, followed by a bilateral subthalamic stimulation implantation-led to the substantial and lasting improvement of the patient’s symptoms.&#x0D;

Characteristics of behavioural addiction in Parkinson’s disease patients with self-reported impulse control disorder and controls matched for levodopa equivalent dose: a matched case–control study

Impulse control disorders (ICD) in Parkinson’s disease (PD) frequently occur, not always as a direct consequence of dopaminergic medication. This study investigated premorbid personality traits and behavioural characteristics in non-demented PD patients with self-reported symptoms of ICD (PD-srICD). From a total of 200 non-demented PD patients who filled out questionnaires assessing symptoms and severity of ICD, those were classified as PD-srICD (n = 32) who reported current occurrence of at least one compulsive behaviour (gambling, sexual behaviour, buying behaviour, or eating). As a control group, 32 patients with no self-reported ICD symptoms were matched for levodopa equivalent daily dose. The demographic, clinical, and premorbid personality profiles were compared between both groups. Frequency of psychological characteristics indicating substance use disorder was evaluated in patients with PD-srICD. Patients with PD-srICD were more frequently male, younger at examination, had earlier PD onset, more depression, higher non-motor burden, less quality of life (p < 0.05, respectively), and more frequently reported premorbid sensation seeking/novelty orientation (p = 0.03) and joyful experience of stress (p = 0.04) than patients in the control group. Of patients with PD-srICD, 90.6% reported at least one behavioural characteristic of substance use disorder, most frequently positive expectations following ICD behaviour and illusional beliefs about its behavioural control. Signs of addiction were common among patients with PD-srICD. Therefore, the profile of psychological characteristics in patients with PD-srICD resembled that of patients with substance use disorder. It can be concluded that dopamine replacement therapy (DRT) alone does not account for PD-srICD and that thorough psychological diagnostics are recommended.

An Institutional Experience of Directional Deep Brain Stimulation and a Review of the Literature

IntroductionDirectional deep brain stimulation (dDBS) has been suggested to have a similar therapeutic effect when compared with the traditional omnidirectional DBS, but with an improved therapeutic window that yields optimized clinical effect owing to the ability to better direct, or “steer,” electric current. We present our single-center, retrospective analysis of our experience in the use of dDBS in patients with movement disorders and provide a review of the literature. Materials and MethodsWe identified all patients with Parkinson disease (PD) and essential tremor (ET) who received a dDBS system between 2018 and 2022 and retrospectively examined characteristics of their longitudinal treatment. A total of 70 leads were identified across 42 patients (28 PD, 14 ET). ResultsThree types of systems were implemented (single-segment activation, 45.2% of patients; multiple independent current control, 50.0%; and local field potential sensing-enabled, 4.7%). The subthalamic nucleus or globus pallidus internus was targeted in PD, and the ventral intermediate nucleus of the thalamus in ET. Across the entire cohort (n = 70 leads), at initial programming, 54.2% of leads (n = 38) were programmed using directional stimulation. At the most recent reprogramming, 58.6% of leads (n = 41) implemented directionality. In patients with PD, the average decrease in levodopa-equivalent daily dose at six months after implantation was 35.4% ± 39.2%. Despite the ability to steer current to relieve stimulation-induced side effects, ten leads in six patients required surgical revision owing to electrode malposition. ConclusionsWe show wide adaptability and implementation of directional stimulation, adding to the growing compendium of real-world uses of dDBS therapy. We used directionality to improve clinical response in both patients with PD and patients with ET and found that its programming flexibility was used at high rates long after implantation and initial programming. In patients with PD, dDBS led to a significant reduction in dopaminergic medication, suggesting sustained clinical improvement. Nonetheless, accurate surgical placement remains necessary to ensure optimal clinical outcomes.