Levodopa Equivalent Dose Research Articles

MELATONIN ON SLEEP IN PARKINSON’S DISEASE: A RANDOMIZED DOUBLE BLIND PLACEBO CONTROLLED TRIAL

BackgroundSleep disturbances are one of the most common non-motor symptoms in Idiopathic Parkinson’s Disease (IPD) patients. However, the effect of melatonin on sleep problems in Parkinson's disease patients is unclear. Aims and objectivesTo study the effect of melatonin on sleep in IPD patients through subjective and objective assessment. MethodsBetween August 2023 to February 2024, we conducted a randomized, double-blind, placebo-controlled trial on IPD patients. We randomized eligible subjects to melatonin (3mg) (n=43) or placebo (n=43) for 8 weeks. The primary endpoint was sleep quality assessed through the Pittsburgh sleep quality index and daytime sleepiness using Epworth sleepiness scale. Secondary endpoints were polysomnographic sleep parameters, quality of life, motor and non-motor symptoms. Assessments were done at baseline and at the end of 8 weeks. ResultsWe screened 107 IPD patients and 86 patients were included in the study. Seventy three patients (melatonin, 35 and placebo, 38) completed the study. The mean change in Pittsburgh Sleep Quality Index (PSQI) score between the two groups was 1.87 (95% CI: 1.5–2.1; p = 0.001) and Epworth Sleepiness Scale (ESS) score was 1.25 (95% CI: 0.80-1.71; p = 0.001) favoring melatonin. The mean difference between the two groups for Non-Motor Symptoms Scale (NMSS) was 6.11 (95% CI 5.27-6.92; p = 0.001), Parkinson's Disease Questionnaire (PDQ 39) 8.12 (95% CI 6.97-9.50; p = 0.001) & Polysomnography (PSG) parameters [sleep latency 8.36 (95% CI 4.38-12.34; p = 0.001) and total sleep time 14.51 (95% CI 5.00-24.41; p = 0.005)] favoring melatonin. Side effects attributable to melatonin were minimal. ConclusionMelatonin is an effective and safe treatment option for sleep problems in PD patients, and beneficial effects on sleep quality are associated with improved non-motor symptoms and quality of life. We need to emphasize the fact that though we had statistically significant changes in our outcomes, it is not clear whether such changes would have real-life impact (meaningfulness) that would be relevant to licensing authorities or management as patients in our study are young, have short disease duration, have high use of anticholinergics and on modest levodopa equivalent dose. So, we are doubtful if this could be generalized to the typical PD population who are older, have longer disease duration and are on potentially sedating medications or not.

Efficacy and safety of safinamide in Parkinson's disease patients with motor fluctuations without levodopa dosage escalation over 18 weeks: KEEP study.

This multicentre, prospective, single-arm study evaluated safinamide as add-on therapy to levodopa in Korean patients with Parkinson's disease (PD) with motor fluctuations with≥1.5 h of "off" time daily, who took levodopa≥3 times/day (n = 199). Baseline levodopa and dopamine agonist doses were maintained without escalation during the 18-week treatment period. Participants received safinamide 50 mg/day for 2 weeks and 100 mg/day thereafter. PD diaries and questionnaires (Parkinson's Disease Questionnaire, PDQ-39; Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale, MDS-UPDRS part 3 and part 4; King's Parkinson's Disease Pain Scale, KPPS; Mini-Mental State Examination, MMSE) were assessed at baseline and at week 18. Treatment-emergent adverse events (TEAEs) were recorded. Mean disease duration was 6.6 years, and mean levodopa equivalent daily dose was 721.1 mg/day. At week 18, significant improvements from baseline were seen for the co-primary endpoints, mean daily "off" time (-1.3±2.4 h, p<0.001) and quality of life (QoL) based on PDQ-39 summary index (-2.7±10.3, p<0.001), Moreover, significant improvements were seen in motor symptoms and motor complications (MDS-UPDRS part 3 and 4), daily "on" time without dyskinesia (all p<0.001) and pain (KPPS; p = 0.013). TEAEs occurred in 40.2% of patients, with most being mild in severity. In conclusion, safinamide at a dosage of 100 mg/day significantly improved motor symptoms, QoL, and pain, and demonstrated a favourable safety profile without levodopa dosage escalation during the 18-week treatment period in Korean patients with PD.Trial registration number and date: NCT05312632, First Posted: April 5, 2022.

Evaluating efficacy and safety of Saffron add-on treatment in improvement of motor and depressive symptoms of patients with Parkinson’s disease: a randomized, double-blind, placebo-controlled clinical trial

AimEvidence has highlighted neuroprotective effects of saffron in animal models of Parkinson’s disease (PD). The present study investigated the efficacy and safety of add-on saffron on motor and depressive symptoms of patients with PD. MethodsThis study was an 8-week, randomized, double-blind, and parallel-group clinical trial. Known cases of PD with depression were randomized to receive either a routine treatment (levodopa or levodopa-equivalent dose of a dopamine agonist) plus saffron capsule (15 mg bid) or routine treatment plus placebo. All participants were assessed using the Hamilton Depression Rating Scale (HAMD), Geriatric Depression Scale-30 (GDS-30), item 3 of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part 1, MDS-UPDRS part 3, and H and Y scale at baseline and at week 8. ResultsA total of 52 patients (25 in saffron and 27 in placebo groups) were included. Our results demonstrated that saffron could not improve motor symptoms of PD patients (F=0.53, df=1, p=0.424). However, repeated-measures analysis showed a significant effect of time × treatment (F=8.24, df=1, p=0.006) on HAMD scores, indicating a greater improvement of depressive symptoms in saffron compared to placebo groups. Our study showed nonsignificant findings regarding the secondary outcome measures (GDS-30, item 3 of MDS-UPDRS part 1, and H and Y scale). We showed that treatment with saffron is safe in PD. ConclusionWe substantiated that add-on treatment with saffron significantly improved depression, but not motor symptoms, in PD. Further trials with larger sample sizes and longer follow-ups are needed to confirm our findings.

Effectiveness and safety of levodopa-entacapone-carbidopa infusion in Parkinson disease: A real-world data study.

Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is a recently developed device-aided therapy for advanced Parkinson disease (PD) patients. The aim of this study was to report real-world evidence about the effectiveness, tolerability, and safety of LECIG in PD patients. A multicenter observational retrospective study of the first patients who initiated LECIG in Spain was performed. All neurologists with an experience of at least two patients treated until 30 March 2024 were invited to participate. Data about effectiveness and safety from the medical records (V0, pre-LECIG; V1, initiation of LECIG; V2, post-LECIG follow-up) with a total of 246 variables were collected. Seventy-three PD patients (61.6% males, 70.1 ± 9.1 years old) from 21 Spanish centers with a mean disease duration of 14.4 ± 6.3 years (range = 5-31) were included. Twenty-six patients (35.6%) were switched directly from levodopa-carbidopa intestinal gel. The mean exposure to LECIG was 177.3 ± 110.5 days (range = 7-476). The mean daily OFF time decreased from 5.2 ± 3 (pre-LECIG) to 1.9 ± 1.8 (post-LECIG; n = 66, p < 0.0001). Global improvement was observed in >85% of the patients. No significant change was detected in the levodopa equivalent daily dose from V0 to V2. Only 7% received 24-h infusion, and 24.7% required more than one cartridge per day at V2. Thirty-four patients (46.6%) had at least one adverse event related to LECIG and/or the device system. Five patients (6.8%) discontinued LECIG. LECIG was safe and effective in advanced PD patients.

Changes in serum uric acid, glutathione, and amyloid-β1-42 levels in Parkinson’s disease patients and their association with disease progression and cognitive decline

Objective This study aims to evaluate the diagnostic significance of serum uric acid (UA), glutathione (GSH), and amyloid-β1-42 (Aβ1-42) levels in relation to disease progression and cognitive impairment in patients with Parkinson’s disease (PD). Methods A total of 209 PD patients with disease duration ranging from 4.0 to 6.8 years were enrolled. Based on the Hoehn-Yahr staging system, patients were classified into Early (n = 67), Medium-term (n = 70), and Advanced (n = 72) stages. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), dividing the cohort into CD (cognitive dysfunction, n = 94) and NO-CD (no cognitive dysfunction, n = 115) groups. Serum UA, GSH, and Aβ1-42 levels were analyzed for correlations with clinical data. Independent risk factors and diagnostic value were determined through multivariable logistic regression models and receiver operating characteristic curve analysis. Results Serum UA and GSH levels progressively declined with advancing disease stage, while Aβ1-42 increased. Compared to the NO-CD group, the CD group showed lower serum UA and GSH levels, and higher Aβ1-42 levels. Serum UA and GSH were inversely correlated with disease duration, levodopa equivalent daily dose, and Unified Parkinson's Disease Rating Scale scores, while Aβ1-42 showed positive correlations. UA (p = 0.006), GSH (p < 0.001), and Aβ1-42 (p = 0.040) were independent predictors of disease stage. Similarly, UA (p = 0.003), GSH (p < 0.001), and Aβ1-42 (p < 0.001) were independent predictors of cognitive dysfunction. The combined assessment of these markers demonstrated a higher area under the curve (AUC) than individual markers for disease and cognitive decline identification. Conclusions Serum UA, GSH, and Aβ1-42 are independent predictors of disease progression and cognitive decline in PD patients. Their combined use offers enhanced diagnostic accuracy for disease staging and cognitive impairment in PD.

Sleep Quality in Parkinson Disease: Clinical Insights and PSQI Reliability Assessment

AbstractSleep disturbances are prevalent in Parkinson disease (PD), encompassing a spectrum from parasomnias like REM sleep behavior disorder to symptoms of sleep-wake cycle dysregulation, such as insomnia and daytime sleepiness. This research investigates sleep quality in PD patients compared with a matched healthy control group and explores the relationships between PD clinical characteristics and sleep parameters. Additionally, the study assesses the reliability of the Pittsburgh Sleep Quality Index (PSQI) for PD patients by examining internal consistency. The study comprises 52 participants, 27 in the PD group and 25 in the healthy control group, matched for sex and age. Sleep quality revealed that PD patients experienced significantly poorer sleep quality than the control group (p = 0.009). Weak correlations were found between PSQI scores and the modified Hoehn and Yahr scale (p = 0.062), with no correlation observed with the daily equivalent dose of levodopa (L-DOPA). The prevalence of poor sleep quality (PSQI score &gt; 5) was 85.1% for PD patients and 68% for the control group. The internal consistency analysis of the PSQI yielded a Cronbach's α of 0.588 for the PD group. While the PSQI demonstrates utility in detecting general sleep abnormalities and gauging patient perceptions of sleep quality in PD, its limitation as a global score is emphasized. The index prioritizes sleep habits and may not fully capture important sleep disorders in this population. These findings underscore the complex relationship between PD and sleep quality, suggesting the need for a comprehensive approach to assess and address sleep disturbances in PD patients.

Prescription trends in Japanese advanced Parkinson's disease patients with non-motor symptoms: J-FIRST.

Non-motor symptoms (NMS) are important factors when selecting treatments for patients with advanced Parkinson's disease (PD). We sought to elucidate the prescribing practices for advanced PD patients with NMS in Japanese clinical practice. We examined the prescription rates and doses of anti-PD drugs, and the use of non-steroidal anti-inflammatory drugs (NSAIDs) in post hoc analyses of a 52-week observational study of 996 PD patients with wearing-off on levodopa-containing therapy and ≥1 NMS. Dopamine agonists were the most frequently prescribed drugs combined with levodopa-containing drugs, followed by entacapone, zonisamide, istradefylline, selegiline, and amantadine. The daily dose of levodopa-containing drugs, rotigotine, entacapone, istradefylline, and droxidopa, and the levodopa-equivalent dose increased during the observation period. In a subgroup analysis of patients stratified by NMS status (improved/unchanged/deteriorated), the deteriorated group had higher prescription rates of entacapone and istradefylline, whereas the improved group had higher prescription rates of NSAIDs and zonisamide at Week 52. Prescriptions varied by geographical region for anti-PD drugs and by NMS status for NSAIDs. There were significant changes in the prescriptions and dosing of selected anti-PD drugs, especially newer drugs. Anti-PD drug and NSAID prescriptions also varied by changes in NMS status and geographic region.

Impact of Duration of Parkinsonism and Antiparkinsonian Drugs on Coagulation Parameters in Patients with Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder involving depletion of dopaminergic neurons. Pathogenetic mechanisms leading to striatonigral degeneration are debatable. Chronic inflammation is proposed as one of the mechanisms. In any disease with underlying inflammation, immune system mediators called cytokines are released, leading to a procoagulant state. Our aim was to study the coagulation parameters in patients with PD and find their correlation with disease duration and antiparkinsonian drugs. This cross-sectional study was conducted between January 2021 and December 2021 in a tertiary care center. Sixty-eight patients with PD were subcategorized based on disease duration (<5 and ≥5 years), number of antiparkinsonian drugs (one drug and ≥2 drugs), and levodopa equivalent daily dose (LEDD; <350 and ≥350 mg). Hemoglobin (Hb), prothrombin time (PT), fibrinogen, bleeding time, and platelet aggregation study with adenosine diphosphate and collagen were assessed. In our cohort of 68 patients, 53 were men and 15 were women. Mean disease duration was 5.97 ± 4.37 years. Hb was negatively associated with LEDD ( P = 0.012) and duration of the disease ( P = 0.02). Similarly, PT was negatively associated with disease duration ( P = 0.041) and number of antiparkinsonian drugs ( P = 0.03). LEDD showed a positive association with collagen-induced platelet aggregation ( P = 0.03). In our study, patients using multiple antiparkinsonian drugs and higher LEDD were observed to have a prothrombotic state. Further studies are needed to confirm these findings.

Lack variation of low slow-wave activity over time in the frontal region in NREM sleep may be associated with dyskinesia in Parkinson's disease.

Levodopa-induced dyskinesia (DYS) adversely affects the quality of life of Parkinson's disease (PD) patients. However, few studies have focused on the relationship between DYS and sleep and electroencephalography (EEG). Our study aimed to establish the objective physiological indicators assessed by polysomnography (PSG) that are associated with DYS in PD patients. We enrolled 122 patients with PD, divided into two groups: PD with DYS (n = 27) and PD without DYS group (non-DYS, n = 95). The demographics and clinical characteristics and sleep assessment in the two groups were collected. More importantly, overnight six-channel PSG parameters were compared in the two groups. We also compared different bands and brain regions of average power spectral density within each group. Compared with the non-DYS group, the DYS group tended to have a significantly higher percentage of nonrapid eye movement sleep (NREM). Gender, levodopa equivalent daily dose (LEDD), rapid eye movement (REM) sleep (min), and the NREM percentage were positively correlated with the occurrence of DYS. After adjusting for gender, disease duration, LEDD, taking amantadine or not, and Montreal Cognitive Assessment (MoCA), NREM%, N3%, and REM (min), the percentage of NREM sleep (p = 0.035), female (p = 0.002), and LEDD (p = 0.005), and REM sleep time (min) (p = 0.012) were still associated with DYS. There was no significant difference in whole-night different bands of average power spectral density between two groups. There was no significant difference in normalized average power spectral density of slow wave activity (SWA) (0.5-2 Hz, 0.5-4 Hz, and 2-4 Hz) of early and late NREM sleep in the DYS group. Dynamic normalized average power spectral density of SWA of low-frequency (0.5-2 Hz) reduction in the frontal region (p = 0.013) was associated with DYS in logistic regression after adjusting for confounding factors. PD patients with DYS have substantial sleep structure variations. Higher NREM percentage and less REM percentage were observed in PD patients with DYS. Dynamic normalized average power spectral density of low-frequency (0.5-2 Hz) SWA reduction in the frontal area could be a new electrophysiological marker of DYS in PD.

Importance of focusing on subjective symptoms to maintain quality of life in patients with Parkinson's disease for over 5 years

Parkinson's disease (PD) is a neurodegenerative disorder that causes a variety of motor and non-motor symptoms (NMS), which affect the patient's quality of life (QOL). This study aimed to compare QOL and background in patients with PD based on the disease duration and investigate the factors affecting QOL. Patients with PD were evaluated based on age, sex, disease duration (≤5 years and > 5 years groups), Mini Mental State Examination (MMSE), Japanese version of Montreal Cognitive Assessment (MoCA-J), Levodopa equivalent daily dose (LEDD), Hoehn and Yahr (HY) severity, movement disorder society-sponsored revision of the unified Parkinson's disease rating scale (MDS-UPDRS) parts I–IV, and QOL using the Parkinson's disease questionnaire (PDQ-8). Overall, 102 patients with PD (58 males; mean age = 70.0 years; mean disease duration = 7.3 years) were included in this study. QOL was significantly correlated (r > 0.30, p < 0.05) with disease duration and MDS-UPDRS parts I–IV total scores. When the PDQ-8 total score was compared with MDS-UPDRS parts I–IV total scores based on disease duration classification, it was positively correlated with the scores for parts I and II in the >5 years group. Moreover, MDS-UPDRS parts I and II total scores appeared to be the factors most significantly affecting QOL. The factors affecting QOL in patients with PD were subjective NMS and motor symptoms. Since, physician-rated motor symptoms were not associated with QOL in patients with >5 years PD, subjective symptoms should be evaluated and treated to maintain QOL.

Levodopa / opicapone as a complement to STN-DBS in clinical practice. A retrospective single-centre analysis.

ObjectiveDeep brain stimulation of the subthalamic nucleus (STN-DBS) is a well-established treatment option in Parkinson's disease with motor and non-motor fluctuations allowing for postoperative reduction of dopaminergic medication. However, evidence is scarce on optimal medication adjustments following STN-DBS implantation. Opicapone allows for long-lasting inhibition of the catechol-O-methyltransferase (COMT) thereby enabling more constant dopaminergic stimulation compared to levodopa alone. However, especially COMT inhibitors are regularly discontinued after STN-DBS surgery. In this single-centre retrospective analysis, we aimed to analyse the clinical phenotype of patients selected for opicapone treatment following STN-DBS implantation and to define clinical determinants of patients requiring more intense dopamine-stabilising strategies after STN-DBS implantation. MethodsA patient cohort treated with STN-DBS + levodopa + opicapone (n = 16) was compared to an age-matched control cohort without opicapone treatment at baseline before and ≥ 5 months post-surgery. As main outcomes we assessed the MDS-UPDRS III and IV scores and reduction of the cumulative dopaminergic medication quantified by the levodopa equivalent dosages (LED). ResultsWhilst the MDS-UPDRS III (median [min – max]) in patients with STN-DBS as well as anatomical electrode positions did not differ significantly between the opicapone 20 [4–40] and control cohort 14 [1–44], the patients selected for opicapone treatment showed a significantly higher degree of dyskinesias already preoperatively as reflected by a UPDRS-IV A subscore of 2 [0–4] compared to controls 0 [0–4]. Postoperatively, the opicapone cohort showed stronger motor fluctuations MDS-UPDRS IV 6 [0–14] compared to the controls 0 [0−10], albeit without statistical significance. Moreover, the opicapone cohort showed significantly less reduction of dopaminergic medication (−36.4 % vs. -46.2 % in the control cohort) following STN-DBS implantation independent from the intake of dopamine agonists. ConclusionThese results indicate a clinical phenotype characterised by more motor fluctuations requiring a more stable dopamine replacement therapy to address the patients' disease biology. In these cases, levodopa + COMT inhibition by opicapone represents a therapeutic approach but determination of the potential clinical benefit requires further prospective studies.

Levodopa-carbidopa intestinal gel for advanced Parkinson's disease: Impact of LRRK2 and GBA1 mutations

BackgroundAdvanced Parkinson's disease (PD) can be treated with Levodopa-Carbidopa Intestinal Gel (LCIG). ObjectiveTo compare descriptive data of LCIG treatment in GBA1-PD and LRRK2-PD. MethodsThis multicenter retrospective study compared clinical data obtained from electronic medical records of PD patients treated with LCIG. Patients were grouped based on their genetic status. ResultsFifty-two iPD, 15 LRRK2-PD and 23 GBA1-PD were included in this study. No difference in daily dose of LCIG or levodopa equivalent daily dose were detected. GBA1-PD had significantly shorter disease duration at LCIG initiation (p = 0.01) and experienced more hallucinations (p = 0.03) compared with LRRK2-PD and iPD. LRRK2-PD and iPD had significantly longer duration of LCIG treatment compared with GBA1-PD (p < 0.01). ConclusionOverall, LCIG treatment was well tolerated in LRRK2-PD and GBA1-PD. GBA1-PD required LCIG earlier in their course of their disease and had higher frequencies of hallucinations during treatment, attesting to a more severe disease course.

Long-term outcomes of subthalamic nucleus deep brain stimulation for Parkinson's disease in Singapore.

Subthalamic nucleus deep brain stimulation (STN-DBS) is a proven treatment modality for Parkinson's disease (PD), reducing dyskinesia and time spent in the "OFF" state. This study evaluates the long-term outcomes of STN-DBS in PD patients up to 10 years post-surgery in Singapore. We conducted a retrospective review of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores, activities of daily living (ADLs), disease milestones, dopaminergic drug prescriptions, and adverse events in patients before and after STN-DBS surgery. A total of 94 PD patients who underwent bilateral STN-DBS were included. STN-DBS reduced time in the "OFF" state by 36.9% at 1 year (P=0.034) and 40.9% at 5 years (P=0.006). Time with dyskinesia did not significantly change. Levodopa equivalent daily dose was reduced by 35.1% by 5 years (P<0.001). MDS-UPDRS-II and III scores increased from 5 years post-DBS by 40.5% and 35.4%, respectively. Independence in ADLs decreased, though not significantly. The prevalence of frequent falls increased at 5 years. Surgery- and device-related adverse events were uncommon and generally mild. STN-DBS provides sustained relief from motor complications and reduced medication requirements in PD patients in Singapore. This study highlights STN-DBS as an effective treatment option, significantly enhancing the quality of life for those with PD.

Long-term outcomes of subthalamic nucleus deep brain stimulation for Parkinson’s disease in Singapore

Introduction: Subthalamic nucleus deep brain stimulation (STN-DBS) is a proven treatment modality for Parkinson’s disease (PD), reducing dyskinesia and time spent in the “OFF” state. This study evaluates the long-term outcomes of STN-DBS in PD patients up to 10 years post-surgery in Singapore. Method: We conducted a retrospective review of Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) scores, activities of daily living (ADLs), disease milestones, dopaminergic drug prescriptions, and adverse events in patients before and after STN-DBS surgery. Results: A total of 94 PD patients who underwent bilateral STN-DBS were included. STN-DBS reduced time in the “OFF” state by 36.9% at 1 year (P=0.034) and 40.9% at 5 years (P=0.006). Time with dyskinesia did not significantly change. Levodopa equivalent daily dose was reduced by 35.1% by 5 years (P&lt;0.001). MDS-UPDRS-II and III scores increased from 5 years post-DBS by 40.5% and 35.4%, respectively. Independence in ADLs decreased, though not significantly. The prevalence of frequent falls increased at 5 years. Surgery- and device-related adverse events were uncommon and generally mild. Conclusion: STN-DBS provides sustained relief from motor complications and reduced medication requirements in PD patients in Singapore. This study highlights STN-DBS as an effective treatment option, significantly enhancing the quality of life for those with PD.

Utilizing Entropy of Cadence to Optimize Cycling Rehabilitation in Individuals With Parkinson’s Disease

Background Previous studies have established that increased Sample Entropy (SampEn) of cadence, a measure of non-linear variability, during dynamic cycling leads to greater improvements in motor function for individuals with Parkinson’s disease (PD). However, there is significant variability in responses among individuals with PD due to symptoms and disease progression. Objectives The aim of this study was to develop and test a paradigm for adapting a cycling exercise intervention using SampEn of cadence and rider effort to improve motor function. Methods Twenty-two participants were randomized into either patient-specific adaptive dynamic cycling (PSADC) or non-adaptive (NA) group. SampEn of cadence was calculated after each of the 12 sessions, and motor function was evaluated using the Kinesia test. Pearson’s correlation coefficient was used to analyze the relationship between SampEn of cadence and motor function improvement. Multiple linear regression (MLR) was used to identify the strongest predictors of motor function improvement. Results Pearson’s correlation coefficient revealed a significant correlation between SampEn of cadence and motor function improvements (R2 = −.545, P = .009), suggesting that higher SampEn of cadence led to greater motor function improvement. MLR demonstrated that SampEn of cadence was the strongest predictor of motor function improvement (β = −8.923, t = −2.632, P = .018) over the BMI, Levodopa equivalent daily dose, and effort. Conclusions The findings show that PSADC paradigm promoted a greater improvement in motor function than NA dynamic cycling. These data will be used to develop a predictive model to optimize motor function improvement after cycling in individuals with PD.

The reduction of LEDD leads to visual dysfunction in patients with PD after STN-DBS: a randomized clinical trial

Background: Medication adjustment after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson’s disease (PD) may influence visual function. However, no clinical trials have been designed specifically to investigate this effect. Objectives: To compare the effects of levodopa equivalent daily dose (LEDD) reduction and non-reduction on visual function in patients with Parkinson’s disease (PD) following STN-DBS. Methods: This was a multi-center, prospective, randomized, double-blinded clinical trial. A total of 208 patients with Parkinson’s disease were referred for DBS between June 2019 and July 2021 and analyzed between June 2023 and July 2023. STN-DBS was performed, and the LEDD was reduced in one study arm but not in the other. The primary outcome measure was visual impairment in Parkinson’s disease questionnaire (VIPD-Q) with or without LEDD reduction 12 months postoperatively, and the secondary outcomes included retinal nerve fiber layer (RNFL) thickness, vessel density, eye-tracking system results, contrast sensitivity and visual field. Results: During the short-term follow-up, DBS implantation and stimulation did not significantly affect visual function (VIPD-Q, baseline vs. 1 month, 9.269±8.385 vs. 8.938±7.666, Mann–Whitney U tests; P=0.6746). In the long-term follow-up, the reduction group demonstrated a significant decline in visual function, RNFL thickness, and vessel density after STN-DBS compared with the control group without STN-DBS (P&lt;0.001). Conclusions: Visual dysfunction, particularly a thinner RNFL and lower vessel density, is related to LEDD reduction after STN-DBS. Prolonged administration of dopamine-mimetic drugs prevents visual symptoms. Thus, physicians should consider LEDD adjustment when patients report visual dysfunction before surgery or severe visual symptoms after STN-DBS.

Safety and efficiency of deep brain stimulation in the elderly patients with Parkinson's disease.

Deep brain stimulation (DBS) is not routinely performed in elderly patients (≥75 years old) to date because of concerns about complications and decreased benefit. This study aimed to evaluate the safety and efficacy of DBS in elderly patients with Parkinson's disease. A retrospective analysis was performed using data from 40 elderly patients from four centers who were treated with neurosurgical robot-assisted DBS between September 2016 and December 2021. These patients were followed up for a minimum period of 2 years, with a subgroup of nine patients followed up for 5-7 years. Patient demographic characteristics, surgical information, pre- and postoperative motor scores, non-motor scores, activities of daily living, and complications were retrospectively analyzed. The mean surgical procedure duration was 1.65 ± 0.24 h, with a mean electrode implantation duration of 1.10 ± 0.23 h and a mean pulse generator implantation duration of 0.55 ± 0.07 h. The mean pneumocephalus volume, electrode fusion error, and Tao's DBS surgery scale were 16.23 ± 12.81 cm3, 0.81 ± 0.23 mm, and 77.63 ± 8.08, respectively. One patient developed a skin infection, and the device was removed. The Unified Parkinson's disease rating scale, Unified Parkinson's disease rating scale of Part III, tremor, rigidity, bradykinesia, axial, and Barthel index for activities of daily living (ADL-Barthel) scores significantly improved at the 2-year follow-up (p < 0.05). The levodopa equivalent daily dose (LEDD) was significantly reduced at the 2-year follow-up (p < 0.05). However, the Montreal cognitive assessment, Hamilton depression scale, and Hamilton anxiety scale scores did not significantly change during the 2-year follow-up (p > 0.05). Additionally, in the subgroup with a 5-year follow-up, the motor symptoms, ADL-Barthel score, and cognitive function worsened over time compared to baseline. However, there was still an improvement in motor symptoms and ADL with DBS on-stimulation compared with the off-stimulation state. The LEDD increased 5 years after surgery compared to that at baseline. Eleven patients had passed away during follow-up, the mean survival time was 38.3 ± 17.3 months after surgery, and the mean age at the time of death was 81.2 (range 75-87) years. Robot-assisted DBS surgery for the elderly patients with Parkinson's disease is accurate and safe. Motor symptoms and ADL significantly improve and patients can benefit from long-term neuromodulation, which may decrease the risk of death.

Awake versus asleep deep brain stimulation for Parkinson's disease: a comprehensive systematic review and meta-analysis.

Deep brain stimulation (DBS) has become an effective and safe treatment in patients with Parkinson's disease (PD) not responding to conventional treatments. With the growing body of literature regarding the use of DBS in different movement disorders, there remain controversies regarding performing awake or asleep DBS. This systematic review provides the most comprehensive review of the literature comparing the two techniques from various aspects in detail. A systematic review of the PubMed, Scopus, Web of Science, and Cochrane Library databases was conducted. All studies comparing any aspects of asleep and awake DBS were included. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies of Interventions tool. Meta-analysis was conducted with consideration of baseline characteristics. Thirty-one studies with 2563 PD patients were included. A total of 1423 patients underwent asleep DBS. The two groups were comparable regarding their baseline characteristics. The follow-up ranged from 3 to 60 months. The two DBS techniques were comparable in terms of motor symptom improvements and levodopa equivalent daily doses. However, the asleep technique showed slightly better improvements in Mattis Dementia Rating Scale and Parkinson's Disease Questionnaire scores. Moreover, the asleep technique was associated with more surgical adverse events, whereas pneumocephalus and psychological disorders such as mood, affect, and cognitive disorders were more common in the awake technique. Subgroup analyses revealed no significant differences in outcomes between asleep and awake DBS when categorized by targeted brain nuclei, use of intraoperative or preoperative imaging, and whether microelectrode recordings were used. These findings suggest comparable clinical outcomes between the two DBS approaches. The two methods had their salient differences in terms of lead passes and specific adverse events. The decision to perform awake or asleep DBS should be based on the patient's preference, the surgeon's experience, the availability of advanced intraoperative imaging, and the patient's tolerance for specific adverse events.

Dual-task performance and brain morphologic characteristics in Parkinson's disease.

Introduction Parkinson's disease (PD) reduces an individual's capacity for automaticity which limits their ability to perform two tasks simultaneously, negatively impacting daily function. Understanding the neural correlates of dual-tasks (DT) may pave the way for targeted therapies. To better understand automaticity in PD, we aimed to explore whether individuals with differing DT performances possessed differences in brain morphologic characteristics. Methods Data were obtained from 34 individuals with PD and 47 healthy older adults including: 1) demographics (age, sex), 2) disease severity (Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn &amp; Yahr, levodopa equivalent daily dose (LEDD)), 3) cognition (Montreal Cognitive Assessment), 4) Levodopa Equivalent Daily Dose, 5) single task- and DT- performance during a DT-Timed-Up-and-Go test utilizing a serial-subtraction task, and 6) Cortical thicknesses and subcortical volumes obtained from volumetric MRI. Participants were categorized as low or high DT performers if their combined DT-effect was greater than the previously determined mean value for healthy older adults (μ=74.2). Nonparametric testing using Quade's ANCOVA was conducted to compare cortical thicknesses and brain volumes between the highDT and lowDT groups while controlling for covariates: age, sex, MDS-UPDRS part III, LEDD, and intracranial volume. Secondarily, similar comparisons were made between the healthy older adult group the highDT and lowDT groups. Lastly, a hierarchical linear regression model was conducted regressing combined DT-effect on covariates (block one) and cortical thicknesses (block 2) in stepwise fashion. Results The highDT group had thicker cortices than the lowDT group in the right primary somatosensory (p=0.001), bilateral primary motor (p=&lt;0.001, left; p=0.002, right), bilateral supplementary motor area (p=0.001, left; p&lt;0.001, right), and mean of the bilateral hemispheres (p=0.001, left; p&lt;0.001, right). Of note, left primary cortex thickness (p=0.002), left prefrontal cortex thickness (p&lt;0.001), and right supplementary motor area thickness (p=0.003) differed when adding a healthy comparison group. Additionally, the regression analysis found that the left paracentral lobule thickness explained 20.8% of the variability in combined DT-effect (p=0.011) beyond the influence of covariates. Conclusions These results suggest regions underlying dual-task performance; specifically, a convergence of neural control relying sensorimotor integration, motor planning, and motor activation to achieve higher levels of DT performance for individuals with PD.

Precision Dopaminergic Treatment in a Cohort of Parkinson's Disease Patients Carrying Autosomal Recessive Gene Variants: Clinical Cohort Data and a Mini Review.

Parkinson's disease (PD) patients harboring recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal recessive PD forms are still scarce. Demographic and treatment data of a cohort of PD carriers of recessive genes (nine homozygous or compound heterozygous PRKN carriers, four heterozygous PRKN carriers, and three biallelic PINK1 carriers) were evaluated. The average levodopa equivalent daily dose (LEDD) was 806.8 ± 453.5 (range 152-1810) in PRKN carriers and 765 ± 96.6 (range 660-850) in PINK1 carriers. The majority responded to low/moderate doses of levodopa. The response to dopamine agonists (DAs) was often favorable both as initial and longitudinal therapy. In total, 8/13 PRKN and 1/3 PINK1 carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate levodopa or DAs. In the era of personalized treatment, the therapeutic approach in recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any levodopa treatment decades after disease initiation. DAs or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in recessive PD genes, including device-aided treatments, will be further discussed.