Levodopa Equivalent Daily Dose Research Articles

Real-World Prescription Patterns For Patients With Young-Onset Parkinson's Disease in China: A Trend Analysis From 2014 to 2019.

Introduction Pharmacotherapy is one of the main treatments for patients with young-onset Parkinson’s disease (YOPD). Although numerous studies on the treatment of YOPD have been published, the real-world prescription patterns of these populations remain unclear in China. Methods A national comprehensive evaluation was performed to reveal the pharmacological treatment patterns in Chinese patients with Parkinson’s disease from 1 January 2014 to 31 December 2019, with patients aged 21–50 years classified as having YOPD for the subgroup analysis. Information on patients and drugs was extracted to analyse the demographic characteristics, prescription patterns, and levodopa equivalent daily dose (LED) during disease progression. Results A total of 1,134 patients with YOPD were included, and the majority were aged 41–50 years. Prescription of L-DOPA/benserazide and pramipexole accounted for more than 30 and 20%, respectively, in each year from 2014 to 2019. There was no difference in prescription patterns in terms of age, sex and geographical areas. Half of the patients with YOPD were on monotherapy, but the proportion decreased from 2016. Correspondingly, the proportion of patients receiving polytherapy increased, especially those who were prescribed more than two anti-Parkinson’s disease drugs. During the disease course, LED showed high variability, which increased over time. Conclusion L-DOPA/benserazide and pramipexole were the most frequently prescribed anti-PD drugs for patients with YOPD in China. There was a slight trend in the transition from monotherapy to polytherapy. LED increased with disease duration. Thus, we provided an overview of the prescription patterns for patients with YOPD in China.

Motor Fluctuations Development Is Associated with Non-Motor Symptoms Burden Progression in Parkinson’s Disease Patients: A 2-Year Follow-Up Study

Objective: The aim of the present study was to analyze the progression of non-motor symptoms (NMS) burden in Parkinson’s disease (PD) patients regarding the development of motor fluctuations (MF). Methods: PD patients without MF at baseline, who were recruited from January 2016 to November 2017 (V0) and evaluated again at a 2-year follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this analysis. MF development at V2 was defined as a score ≥ 1 in the item-39 of the UPDRS-Part IV, whereas NMS burden was defined according to the Non-motor Symptoms Scale (NMSS) total score. Results: Three hundred and thirty PD patients (62.67 ± 8.7 years old; 58.8% males) were included. From V0 to V2, 27.6% of the patients developed MF. The mean NMSS total score at baseline was higher in those patients who developed MF after the 2-year follow-up (46.34 ± 36.48 vs. 34.3 ± 29.07; p = 0.001). A greater increase in the NMSS total score from V0 to V2 was observed in patients who developed MF (+16.07 ± 37.37) compared to those who did not develop MF (+6.2 ± 25.8) (p = 0.021). Development of MF after a 2-year follow-up was associated with an increase in the NMSS total score (β = 0.128; p = 0.046) after adjustment to age, gender, years from symptoms onset, levodopa equivalent daily dose (LEDD) and the NMSS total score at baseline, and the change in LEDD from V0 to V2. Conclusions: In PD patients, the development of MF is associated with a greater increase in the NMS burden after a 2-year follow-up.

Advanced-Stage Parkinson's Disease: From Identification to Characterization Using a Nationwide Database.

As Parkinson's disease (PD) progresses, response to oral medications decreases and motor complications appear. Timely intervention has been demonstrated as effective in reducing symptoms. However, current instruments for the identification of these patients are often complicated and inadequate. It has been suggested that anti-PD intensified therapy (IT) can serve as a proxy for increased burden of disease. To explore whether IT aligns with events reflecting advanced PD (APD) burden. This was a retrospective analysis of PD beneficiaries in the second-largest healthcare provider in Israel. Patients with PD diagnosed between January 2000 and June 2018 and treated with levodopa (l-dopa) ≥5 times/day and/or ≥1000 mg l-dopa equivalent daily dose were defined as the IT cohort (n=2037). Treated patients with PD not fulfilling this criterion were defined as the nonintensified therapy (NIT) cohort (n=3402). Point prevalence and 5- and 10-year cumulative incidence of IT were assessed. Baseline demographic and comorbidities, 1-year healthcare resource use, health costs, and time to clinical events were assessed and compared between cohorts. IT was associated with significantly (P< 0.05) higher healthcare resource use compared with NIT. In turn, IT patients incurred higher healthcare costs (P< 0.001) and were at greater risk for mortality, hospitalization, disability, and device-aided therapy use (P< 0.001, for all comparisons). Treatment intensity can serve as an objective and robust indicator of more APD. This readily extractable marker can be easily integrated into electronic medical record alerts to actively target more advanced patients and to guide risk-appropriate care.

Long-term directional deep brain stimulation: Monopolar review vs. local field potential guided programming

BackgroundDirectional subthalamic stimulation in Parkinson's disease can increase stimulation threshold for adverse effects and widen the therapeutic window. However, selection of programming settings is time consuming, requiring a thorough monopolar clinical review. To overcome this, programming may be guided by intraoperatively recording local field potential beta oscillations (13–35 Hz). Objectives1) Evaluate whether the power of beta oscillations recorded intraoperatively can predict the clinically most effective directional contacts; and 2) assess long-term directional stimulation outcomes between patients programmed based on clinical monopolar review and patients programmed based on beta activity. MethodsWe conducted a non-randomized, prospective study with 24 Parkinson's disease patients divided into two groups. In group A (14 patients, 2016–2018), we investigated whether beta activity in the directional contacts correlated with clinical efficacy. Stimulating parameters were selected according to clinical monopolar review and mean follow-up was 27 months. In group B (10 patients, 2018–2019), stimulating parameters were selected according to beta activity and mean follow-up was 13 months. ResultsNeurophysiological results showed a strong correlation between clinical efficacy and the low-beta sub-band. Contacts with highest beta peaks increased the therapeutic window by 25%. Selecting the two contacts with highest beta peaks provided an 82% probability of selecting the best clinical contact. Clinical results showed similar improvements in group A (motor score, 72% reduction; levodopa-equivalent daily dose, 65% reduction) and B (72% and 63% reduction, respectively), maintained at long-term follow-up. ConclusionsOur results validate the long-term efficacy of directional stimulation guided by intraoperative local field potential beta oscillations.

Fiber selectivity of peripheral neuropathy in patients with Parkinson's disease.

To determine the function of each type of peripheral nerve fiber and investigate the possible role of levodopa (LD) in peripheral neuropathy (PN) in Parkinson's disease (PD) patients. We enrolled 60 patients with idiopathic PD. All PD patients were divided into three groups: levodopa exposure >3years (LELD), levodopa exposure ≤3years (SELD) and de novo patients with PD (NOLD). The current perception threshold (CPT), which was measured by Neurometer at 2000, 250 and 5Hz, the level of homocysteine, Vitamin B12 and folic acid in plasma, were compared with those of sex- and age-matched healthy controls (HCs). Current perception threshold was higher at 250Hz (p<.05) and 5Hz (p<.05) in the LELD group than the NOLD, SELD, and control group. CPT was lower at 5Hz in the NOLD than in the HCs group (p<.05). The CPT of the more affected side of PD patients was positively correlated with H-Y stage at 5Hz current stimulation (r=.42, p=.01). Multivariate logistic regression analysis showed that elevated homocysteine levels were the risk factor of sensory nerve injury in PD patients (p<.01). Serum homocysteine levels were positively correlated with levodopa (LD) daily dose, LD equivalent daily dose, and LD cumulative lifetime dose (p<.05). Peripheral neuropathy in PD patients can occur in the early stage of PD exhibiting as hyperesthesia and is fiber selectivity, especially for Aδ and C nerve fibers. PN in PD patients is related to PD itself and long-term LD exposure. Elevated plasma homocysteine is a risk factor for PN in PD patients.

Gender gap in deep brain stimulation for Parkinson\u2019s disease

Previous studies have shown less access to deep brain stimulation (DBS) for Parkinson’s disease (PD) in women compared to men raising concerns about a potential gender gap resulting from nonclinical factors or gender differences in clinical efficacy for postoperative quality of life (QoL), motor, and nonmotor symptoms (NMS) outcomes. This was a cross-sectional and a longitudinal, prospective, observational, controlled, quasi-experimental, international multicenter study. A total sample size of 505 consisted of 316 consecutively referred patients for DBS indication evaluation at the University Hospital Cologne (01/2015–09/2020) and 189 consecutively treated patients at DBS centers in the University Hospitals Cologne and Marburg, Salford’s Royal Hospital Manchester, and King’s College Hospital London. In the cross-sectional cohort, we examined gender proportions at referral, indication evaluations, and DBS surgery. In the longitudinal cohort, clinical assessments at preoperative baseline and 6-month follow-up after surgery included the PD Questionnaire-8, NMSScale, Scales for Outcomes in PD-motor scale, and levodopa-equivalent daily dose. Propensity score matching resulted in a pseudo-randomized sub-cohort balancing baseline demographic and clinical characteristics between women with PD and male controls. 316 patients were referred for DBS. 219 indication evaluations were positive (women n = 102, respectively n = 82). Women with PD were disproportionally underrepresented in referrals compared to the general PD population (relative risk [RR], 0.72; 95%CI, 0.56–0.91; P = 0.002), but more likely to be approved for DBS than men (RR, 1.17; 95%CI, 1.03–1.34; P = 0.029). Nonetheless, their total relative risk of undergoing DBS treatment was 0.74 (95%CI, 0.48–1.12) compared to men with PD. At baseline, women had longer disease duration and worse dyskinesia. Exploring QoL domains, women reported worse mobility and bodily discomfort. At follow-up, all main outcomes improved equally in both genders. Our study provides evidence of a gender gap in DBS for PD. Women and men with PD have distinct preoperative nonmotor and motor profiles. We advocate that more focus should be directed toward the implementation of gender equity as both genders benefit from DBS with equal clinical efficacy. This study provides Class II evidence of beneficial effects of DBS in women with PD compared to male controls.

Comparison of Montreal cognitive assessment and Mattis dementia rating scale in the preoperative evaluation of subthalamic stimulation in Parkinson's disease.

IntroductionThe preoperative evaluation of Parkinson’s Disease (PD) patients for subthalamic nucleus deep brain stimulation (STN-DBS) includes the assessment of the neuropsychological status of the patient. A widely used preoperative test is the Mattis Dementia rating scale (MDRS). However, the Montreal cognitive assessment (MoCA) has also been proven to be a sensitive, time-sparing tool with high diagnostic validity in PD. We evaluate the utility of the MoCA as a preoperative screening test for PD patients undergoing bilateral STN-DBS.MethodsIn this single-centre, retrospective study, we analysed pre- and postoperative assessments of MoCA, MDRS, Movement disorder society-Unified PD Rating Scale-motor examination, PD Questionnaire-39 and levodopa equivalent daily dose. Longitudinal outcome changes were analysed using paired t-test, Pearson’s correlation coefficient, linear regression and CHAID (chi-square automatic interaction detector) regression tree model.ResultsClinical motor and cognitive scores of 59 patients (61.05±7.73 years, 24 females) were analysed. The MoCA, but not the MDRS, identified significant postoperative cognitive decline in PD patients undergoing STN-DBS. The preoperative MoCA score correlated with postoperative quality of life improvement, whereas the MDRS did not. PD patients with a MoCA score ≤ 23 points had a significant decline of quality of life after DBS surgery compared to patients > 23 points.ConclusionThis study identifies the MoCA as an alternative test within the preoperative evaluation of PD patients for the detection of neuropsychological deficits and prediction of the postoperative improvement of quality of life.

Association between sleep disturbances and pain subtypes in Parkinson's disease.

To explore the influence of sleep disturbances on the various pain subtypes experienced by patients with Parkinson's disease (PD). A cohort of eighty-eight patients with PD-related pain was recruited for this study. Their demographic and clinical features, including age, disease duration, levodopa equivalent daily dose (LEDD), and scores on the Unified Parkinson's Disease Rating Scale-III (UPDRS III), Hoehn-Yahr Scale (H&Y), Pittsburgh Sleep Quality Index (PSQI), King's Parkinson's disease Pain Scale (KPPS), visual analog scale (VAS), Mini-Mental State Examination (MMSE), activities of daily living scale (ADL), Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Rating Scale (HAMA), were recorded. The prevalence of sleep disorders was 76.1% in patients with PD-related pain. Among these patients, the group of poor sleep had more severe motor symptoms, more anxiety and depression symptoms, lower functional independence, and experienced more pain, such as musculoskeletal pain, chronic pain, fluctuation related pain, nocturnal pain, and discoloration/edema/swelling (p < 0.05). In addition, PSQI scores correlated positively with the scores of all 7 domains in KPPS (p < 0.05). H&Y stage and PSQI were significant independent variables explaining 50.0% of the variance in KPPS scores. Sleep disturbance showed an association with pain in PD patients and may have a greater effect on some certain subtypes of PD-related pain than others.

Factors Contributing to Malnutrition in Parkinson's Disease Patients With Freezing of Gait.

Background and PurposeLittle is known about the nutritional status and clinical characteristics of patients with Parkinson's disease with freezing of gait (PDFOG). The purpose of this study was to describe the relationship between nutritional status and characteristics of patients with PDFOG.MethodsIn this cross-sectional study, 178 PDFOG patients were recruited and classified as nutritionally normal or at risk of malnutrition/already malnourished based on their Mini Nutritional Assessment (MNA) scores. Each participant underwent a structured questionnaire, physical examination and routine serum biochemical tests.ResultsWe found that 44.4 and 37.1% of PDFOG patients were malnourished [mini nutritional assessment (MNA) score <17] and at risk of malnutrition (17 ≤ MNA score ≤ 23.5), respectively. Compared to patients with normal nutrition, PDFOG patients with malnutrition and at risk of malnutrition had longer duration of Parkinson's disease (PD) and freezing of gait (FOG), more levodopa equivalent daily doses (LEDD), lower body mass index (BMI), more motor symptoms according to the Unified PD Rating Scale-III (UPDRS-III) and non-motor symptoms according to the PD Non-motor Symptoms Questionnaire (PD-NMS) (P < 0.05). Uric acid, albumin, prealbumin, and total cholesterol (TC) differed between the two groups (P < 0.05). High Hoehn and Yahr (H-Y) stage, high Freezing of Gait Questionnaire (FOGQ) scores, low TC and low uric acid were risk factors for malnutrition in patients with PDFOG.ConclusionOur results showed disease severity, motor symptoms, TC levels and uric acid levels were all associated with nutritional status in patients with PDFOG. This study suggest early discovery of the nutritional status of PDFOG patients is important.

Elevation of Plasma Homocysteine and Minor Hallucinations in Parkinson's Disease: A Cross-Sectional Study.

Purpose Minor hallucinations (MHs) are the most common psychotic phenomena in Parkinson's disease (PD), and it has important clinical and prognostic implications in PD. Plasma homocysteine (Hcy) has been reported to predict the outcome of PD; whether or not Hcy is associated with MH is not known. We aim to investigate the Hcy level and related factors in patients with PD and MH. Methods We conducted a cross-sectional study and included 99 patients with PD, 34 with MH, and 65 without any hallucinations. The clinical and demographic data of the patients with and without hallucinations were compared. Hcy-related clinical factors were also analyzed. Results The plasma Hcy level was higher in MH patients than in patients without hallucinations, and the result was more pronounced in male patients than in female patients. Differences were also observed when the groups were divided on the basis of levodopa equivalent daily dose and disease duration. The high Hcy concentration was correlated with some symptoms in patients with MH, including motor dysfunction and nonmotor symptoms, such as symptoms of the gastrointestinal tract, angiocarpy, sleep/fatigue, and poor visuospatial/executive function. Conclusions Results indicated a higher plasma Hcy concentration in MH patients than in their counterparts and revealed that Hcy is associated with certain motor and nonmotor symptoms in patients with MH. Hcy may be a marker of MH and have important therapeutic implications in PD.

Pain Assessment in Chinese Parkinson’s Disease Patients Using King’s Parkinson’s Disease Pain Scale

PurposeTo assess Parkinson’s disease (PD)-related pain using the Chinese translation of King’s Parkinson’s disease Pain Scale (KPPS).Patients and MethodsA cohort of 200 patients with primary PD was recruited for this study. Their demographic and clinical features, including age, disease duration, levodopa equivalent daily dose (LEDD), and scores on the Unified Parkinson’s Disease Rating Scale-III (UPDRS III), Hoehn-Yahr Scale (H&Y), Mini-Mental State Examination (MMSE), Activities of Daily Living Scale (ADL), Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Pittsburgh Sleep Quality Index (PSQI), Visual Analogue Scale (VAS) and KPPS, were recorded.ResultsThe prevalence of PD-related pain was 44.5%. Among the patients with PD-related pain, the average KPPS score was 41.2 ± 26.8. Pain was most commonly located in the lower limbs (60.7%), upper limbs (22.5%) and waist (21.3%). The most common pain type was musculoskeletal pain (68.5%). Compared with the PD group without pain, the PD group with pain had a longer disease duration (p = 0.022), higher LEDD (p = 0.008), higher UPDRSIII score (p = 0.018), higher H&Y stage (p = 0.003), higher HAMD score (p < 0.001), higher HAMA score (p < 0.001), lower ADL score (p = 0.046) and higher PSQI score (p < 0.001). PD-related pain was correlated with the H&Y stage and the PSQI score (p < 0.05). Cut-off points of 0, 34, and 70 were obtained to discriminate pain severity levels between no pain, mild, moderate, and severe pain, respectively.ConclusionChinese version of KPPS is not only an easy tool for characterization and scoring of pain in PD patients but also has the ability to distinguish between different levels of pain severity.

Asleep deep brain stimulation with intraoperative magnetic resonance guidance: a single-institution experience.

Deep brain stimulation (DBS) is traditionally performed on an awake patient with intraoperative recordings and test stimulation. DBS performed under general anesthesia with intraoperative MRI (iMRI) has demonstrated high target accuracy, reduced operative time, direct confirmation of target placement, and the ability to place electrodes without cessation of medications. The authors describe their initial experience with using iMRI to perform asleep DBS and discuss the procedural and radiological outcomes of this procedure. All DBS electrodes were implanted under general anesthesia by a single surgeon by using a neuronavigation system with 3-T iMRI guidance. Clinical outcomes, operative duration, complications, and accuracy were retrospectively analyzed. In total, 103 patients treated from 2015 to 2019 were included, and all but 1 patient underwent bilateral implantation. Indications included Parkinson's disease (PD) (65% of patients), essential tremor (ET) (29%), dystonia (5%), and refractory epilepsy (1%). Targets included the globus pallidus pars internus (12.62% of patients), subthalamic nucleus (56.31%), ventral intermedius nucleus of the thalamus (30%), and anterior nucleus of the thalamus (1%). Technically accurate lead placement (radial error ≤ 1 mm) was obtained for 98% of leads, with a mean (95% CI) radial error of 0.50 (0.46-0.54) mm; all leads were placed with a single pass. Predicted radial error was an excellent predictor of real radial error, underestimating real error by only a mean (95% CI) of 0.16 (0.12-0.20) mm. Accuracy remained high irrespective of surgeon experience, but procedure time decreased significantly with increasing institutional and surgeon experience (p = 0.007), with a mean procedure duration of 3.65 hours. Complications included 1 case of intracranial hemorrhage (asymptomatic) and 1 case of venous infarction (symptomatic), and 2 patients had infection at the internal pulse generator site. The mean ± SD voltage was 2.92 ± 0.83 V bilaterally at 1-year follow-up. Analysis of long-term clinical efficacy demonstrated consistent postoperative improvement in clinical symptoms, as well as decreased drug doses across all indications and follow-up time points, including mean decrease in levodopa-equivalent daily dose by 53.57% (p < 0.0001) in PD patients and mean decrease in primidone dose by 61.33% (p < 0.032) in ET patients at 1-year follow-up. A total of 205 leads were placed in 103 patients by a single surgeon under iMRI guidance with few operative complications. Operative time trended downward with increasing institutional experience, and technical accuracy of radiographic lead placement was consistently high. Asleep DBS implantation with iMRI appears to be a safe and effective alternative to standard awake procedures.

Tau and Amyloid-β Peptides in Serum of Patients With Parkinson's Disease: Correlations With CSF Levels and Clinical Parameters.

Relevance of blood-based biomarkers is increasing into the neurodegenerative diseases field, but data on Parkinson's disease (PD) remain still scarce. In this study, we used the SiMoA technique to measure serum content of total tau protein and amyloid-β peptides (Aβ-42, Aβ-40) in 22 PD patients and ten control subjects. Serum levels of each biomarker were correlated with the respective CSF levels in both the groups; in PD patients, also the correlations between serum biomarkers and main clinical parameters were tested (motor, non-motor, cognitive scores and levodopa equivalent daily dose). Serum biomarkers did not exhibit quantitative differences between patients and controls; however, only PD patients had inter-fluids (serum-CSF) associations in tau and amyloid-β-42 levels. Moreover, serum content of tau protein was inversely correlated with cognitive performances (MoCA score). These findings, albeit preliminary, indicate that brain-derived peptides may change in parallel in both peripheral blood and CSF of PD patients, eventually even in association with some clinical features. Further studies are now needed to validate the use of blood-based biomarkers in PD.

Energy Delivered by Subthalamic Deep Brain Stimulation for Parkinson Disease Correlates With Depressive Personality Trait Shift

ObjectivesDespite the large amount of literature examining the potential influence of subthalamic nucleus deep brain stimulation (STN-DBS) on psychiatric symptoms and cognitive disorders, only a few studies have focused on its effect on personality. We investigated the correlation between total electrical energy delivered (TEED) and the occurrence of depressive traits in patients with Parkinson disease (PD) after one year of DBS. Materials and MethodsOur study involved 20 patients with PD (12 women, mean [±SD] age 57.60 ± 7.63 years) who underwent bilateral STN-DBS, whose personality characteristics were assessed using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), according to the core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD) procedure. ResultsWe found that despite a marked improvement in motor functions and quality of life after 12 months, patients showed a significant increase in MMPI-2 subscales for depression (D scale and Depression scale) and in other content component scales (low self-esteem, work interference, and negative treatment indicators). Interestingly, only the TEED on the right side was inversely correlated with the changes in scale D (rs = −0.681, p = 0.007), whereas depressive traits did not correlate with disease duration, levodopa equivalent daily dose (LEDD) reduction, patient’s age, or severity of motor symptoms. ConclusionsOur preliminary observations indicate that despite the excellent motor outcome and general improvement in quality of life, DBS treatment can result in patients poorly adjusting to their personal, familiar, and socio-professional life. Different influences and multiple factors (such as TEED, intra/postsurgical procedure, coping mechanisms, and outcome expectations) may affect depressive traits. Further advances are expected to improve stimulation methods.

Dopaminergic medication reduces interhemispheric hyper-synchronization in Parkinson's disease

IntroductionWe previously reported on interhemispheric cortical hyper synchronization in PD. The aim of the present study was to address the hypothesis that increased interhemispheric cortical synchronization in PD is related to dopamine deficiency and is correlated with motor function. MethodsWe studied participants with PD and characterized cortical synchronization with reference to brain regions. Electroencephalography (EEG) was recorded from 20 participants with PD while OFF and ON their dopaminergic medications (two separate visits), during quiet standing and straight-line walking. Cortical interactions in the theta, alpha, beta, and gamma brain wave frequency bands were evaluated using interhemispheric phase synchronization (inter-PS). ResultsInter-PS values were found to be significantly higher during the OFF state as compared to the ON state in standing and walking trials for theta, alpha and beta bands.In addition, inter-PS reduction from OFF to ON was associated with mobility improvement evaluated by the Timed Up and Go test, and with daily levodopa equivalent dose across individuals. Higher differences in inter-PS values between OFF and ON states were evident mainly in the occipital-parietal cortex. ConclusionsPersons with PD have increased inter-PS during the OFF state compared to their ON state, and this increase in inter-PS is associated with the clinical improvement between OFF and ON. We speculate that these findings, together with previous evidence of higher inter-PS in PD as compared to healthy older adults, reflect neuronal processes consequential to asymmetric subcortical dopamine deficiency.

Antiparkinsonian Drug Reduction After Directional Versus Omnidirectional Bilateral Subthalamic Deep Brain Stimulation

BackgroundSeveral pilot trials and the Clinical Evaluation of the Infinity Deep Brain Stimulation System (PROGRESS) study have found that directional stimulation can provide a wider therapeutic window and lower therapeutic current strength than omnidirectional stimulation. ObjectiveWe conducted a single-center, open-label, registry-based, comparative trial to test the hypothesis that directional stimulation can be associated with a greater reduction in the total daily dose of antiparkinsonian medications (ApMeds) than omnidirectional stimulation. Materials and MethodsA total of 52 patients with directional and 57 subjects with omnidirectional bilateral subthalamic deep brain stimulation (STN-DBS) were enrolled. Preoperatively and 12 months postoperatively, the dose of different ApMeds, the number of tablets used daily, the severity of motor and nonmotor symptoms using the Movement Disorder Society–sponsored Unified Parkinson Disease Rating Scale, and the health-related quality of life (HRQoL) using the 39-item Parkinson’s Disease Questionnaire (PDQ-39) were assessed. ResultsAccording to the changes in the levodopa equivalent daily dose, directional STN-DBS led to a 13% greater reduction in the total daily dose of ApMed. The 10.3% greater reduction in the dose of levodopa was the main contributor to this difference. The number of different ApMed types also could be decreased in a greater manner with directional stimulation. The improvement in the severity of motor and nonmotor symptoms was comparable; however, we detected a 15.8% greater improvement in the global HRQoL among patients with directional stimulation according to the changes in the summary index of the PDQ-39. The total electrical energy delivered per second was comparable between the groups at 12-month postoperative visit, whereas the amplitude of stimulation was significantly lower and the impedance was significantly higher with directional leads. ConclusionsDirectional programming can further increase the reduction in the total daily dose of ApMed after STN-DBS. In addition, directional stimulation can have additional beneficial effects on the global HRQoL. The greater reduction of ApMed doses did not require more energy-consuming stimulation with directional stimulation.

HP18: Analysis of functional connectivity in non-motor symptoms in Parkinson’s Disease

The underlying pathophysiology of the occurrence of non-motor symptoms (NMSs) in Parkinson’s disease (PD) have been unclear. Our study aims to evaluate the association between NMSs and implications of brain functional connectivity (FC) in PD patients. Methods: A total of 20 sporadic PD patients were included in this study, and were evaluated for motor symptoms and NMSs, including hallucination, REM sleep behavior disorder (RBD), cognitive impairment, pain, anxiety, and decreased motivation. We investigated the FC in brain network quantified by electroencephalography (EEG) coherence analysis in whole-brain and regional coherence, using phase-coupling for each frequency. Results: Whole-brain coherence values were compared between NMS-positive and -negative patients. Hallucination and cognitive impairment positive patients showed a significant decrease in coherence in theta and alpha ranges than negative (p<0.05). RBD positive patients showed a significant decrease in coherence in the alpha range than negative (p<0.05). Pain-positive patients showed a trend for higher whole-brain coherence in the alpha range than negative (p=0.11). Whole-brain coherence showed a strong correlation with disease duration (r=−0.395), MDS-UPDRS total scores (r=−0.489) and MMSE (r=0.490), by contrast no correlation with age and levodopa equivalent daily dose. The regional coherence in the left frontal-left parietal region showed a higher correlation with the MMSE scores (r=0.583) than that in the right frontal-left parietal region (r=0.456). Conclusions: The difference of EEG coherence across each NMS may indicate a compensatory response of the brain to the neuropathology of PD. Our results suggested decreased brain efficiency and impaired neural synchronization in PD patients with NMSs.

The quality of life in patients with Parkinson's disease: Focus on gender difference.

BackgroundTo improve understanding of gender differences on quality of life (QoL) in patients with Parkinson's disease (PWP) of a different race, the differences of clinical features and health‐related quality of life (HRQoL) between male and female PWP were studied in a small cohort early to middle stage of Chinese PWP.MethodsA cross‐sectional study was carried out. PWP were consecutively included from April 2020 to July 2021 in Beijing Rehabilitation Hospital. HRQoL, motor symptoms, and nonmotor symptoms in each patient were evaluated. The differences of demographic, motor symptoms assessments, nonmotor symptoms assessments, and QoL between two gender groups were tested using t‐test statistics, Mann–Whitney–Wilcoxon test, or χ 2 depending on the data type. To eliminate the possible factors contributing to the QoL, linear regression models were constructed to sort out the effect of gender.ResultsOne hundred and sixty‐two Parkinson's disease (PD) patients were included. Demographic, clinical characteristics, and symptom scale assessments had no statistical differences except for levodopa equivalent daily dose, Hamilton Anxiety Rating Score, REM sleep behavior disorder sleep questionnaire, and Hyposmia Rating Scale score. After baseline imbalance corrections, a significantly higher score of PD Questionnaire‐39 (PDQ‐39) in female than in male patients(p<.05) was found. In the questionnaire, summary Index and bodily discomfort, stigma, and emotional well‐being subscores were the main contribution differences.ConclusionsGender differences are associated with the QoL in the early to middle stage PWP in China. Female patients have poorer QoL than male patients, especially bodily discomfort, stigma, and emotional well‐being.

Longitudinal Change and Progression Indicators Using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale in Two Independent Cohorts with Early Parkinson's Disease.

The MDS-Unified Parkinson's disease (PD) Rating Scale (MDS-UPDRS) is the most used scale in clinical trials. Little is known about the predictive potential of its single items. To systematically dissect MDS-UPDRS to predict PD progression. 574 de novo PD patients and 305 healthy controls were investigated at baseline (BL) in the single-center DeNoPa (6-year follow-up) and multi-center PPMI (8-year follow-up) cohorts. We calculated cumulative link mixed models of single MDS-UPDRS items for odds ratios (OR) for class change within the scale. Models were adjusted for age, sex, time, and levodopa equivalent daily dose. Annual change and progression of the square roots of the MDS-UDPRS subscores and Total Score were estimated by linear mixed modeling. Baseline demographics revealed more common tremor dominant subtype in DeNoPa and postural instability and gait disorders-subtype and multiethnicity in PPMI. Subscore progression estimates were higher in PPMI but showed similar slopes and progression in both cohorts. Increased ORs for faster progression were found from BL subscores I and II (activities of daily living; ADL) most marked for subscore III (rigidity of neck/lower extremities, agility of the legs, gait, hands, and global spontaneity of movements). Tremor items showed low ORs/negative values. Higher scores at baseline for ADL, freezing, and rigidity were predictors of faster deterioration in both cohorts. Precision and predictability of the MDS-UPDRS were higher in the single-center setting, indicating the need for rigorous training and/or video documentation to improve its use in multi-center cohorts, for example, clinical trials.

Axial Impairment Following Deep Brain Stimulation in Parkinson's Disease: A Surgicogenomic Approach.

Background: Postoperative outcome following deep brain stimulation (DBS) of the subthalamic nucleus is variable, particularly with respect to axial motor improvement. We hypothesized a genetic underpinning to the response to surgical intervention, termed “surgicogenomics”.Objective: We aimed to identify genetic variants associated with clinical heterogeneity in DBS outcome of Parkinson’s disease (PD) patients that could then be applied clinically to target selection leading to improved surgical outcome.Methods: Retrospective clinical data was extracted from 150 patient’s charts. Each individual was genotyped using the genome-wide NeuroX array tailored to study neurologic diseases. Genetic data were clustered based on surgical outcome assessed by comparing pre- and post-operative scores of levodopa equivalent daily dose and axial impairment at one and five years post-surgery. Allele frequencies were compared between patients with excellent vs. moderate/poor outcomes grouped using a priori defined cut-offs. We analyzed common variants, burden of rare coding variants, and PD polygenic risk score.Results:NeuroX identified 2,917 polymorphic markers at 113 genes mapped to known PD loci. The gene-burden analyses of 202 rare nonsynonymous variants suggested a nominal association of axial impairment with 14 genes (most consistent with CRHR1, IP6K2, and PRSS3). The strongest association with surgical outcome was detected between a reduction in levodopa equivalent daily dose and common variations tagging two linkage disequilibrium blocks with SH3GL2.Conclusion:Once validated in independent populations, our findings may be implemented to improve patient selection for DBS in PD.