Levodopa Equivalent Daily Dose Research Articles

Musculoskeletal Pain in Parkinson's Disease.

BackgroundMusculoskeletal pain is commonly experienced in patients with Parkinson's disease (PD). Few studies have investigated the clinical characteristics and risk factors associated with musculoskeletal pain.ObjectivesTo investigate the distribution, clinical characteristics, and factors associated with musculoskeletal pain in a large sample of patients with PD.MethodsWe enrolled 452 patients from two clinics and used a standardized questionnaire to collect demographic and clinical information. Musculoskeletal pain was diagnosed based on the Ford Classification System, and pain severity was assessed with the numeric rating scale (NRS). Multivariate regression models explored the association between clinical features of PD and quality of life and pain.ResultsTwo hundred and six patients (45.58%) reported musculoskeletal pain, typically in their lower limbs and backs. Levodopa resulted in a ≥30% reduction in pain intensity scores in 170 subjects. Female sex (odds ratio [OR], 1.57; 95% CI, 1.07–2.29) and Levodopa-equivalent daily doses (LEDDs; OR, 3.35; 95% CI, 1.63–6.59) were associated with an increased risk for musculoskeletal pain. Pain duration (p = 0.017), motor symptoms (p < 0.001), and depression (p < 0.001) were significantly associated with quality of life.ConclusionsThe lower limbs and back are common sites of musculoskeletal pain in patients with PD, and up to 82.52% of patients were responsive to Levodopa. Female sex and LEDDs are associated with musculoskeletal pain, suggesting that dopamine deficiencies, and not the motor and non-motor impairment, might be the most critical baseline risk factor of musculoskeletal pain.

Clinical Characteristics of Minor Hallucinations in Chinese Parkinson's Disease Patients.

BackgroundPsychotic symptoms are common in Parkinson's disease (PD). However, the clinical characteristics of PD psychosis (PDP) have been rarely reported in Chinese PD patients. We aimed to categorize PDP in a PD cohort and its relationship to other clinical characteristics.MethodsA total of 149 Chinese PD patients were consecutively enrolled, and idiopathic PD patients were recruited in the study. The symptoms of PDP were assessed with the enhanced Scale for the Assessment of Positive Symptoms in PD. Then, the patients were classified into a PD-control group, isolated minor hallucination (MH) group, and complex MH group, and clinical and demographic data of different groups were compared.ResultsParkinson's disease psychosis was present in 40.3% (60/149) of our patients. The most common PDPs were MHs, present in 32.9% (49 of 149) of the cohort. Compared to patients without MHs, patients with MHs were older, had a longer disease duration, a higher levodopa equivalent daily dose, more severe motor symptoms, dyskinesia, a higher rate of rapid eye movement sleep behavior disorders, frontal lobe function impairments, and a higher percentage of cognitive impairment. Logistic regression analysis showed that advanced Hoehn-Yahr stage [odds ratio (OR): 2.697, p = 0.007)] and frontal lobe function impairment (OR: 0.684, p = 0.003) were independent risk factors for MHs.ConclusionMHs were frequent non-motor symptoms in PD patients. It was associated with increased motor and non-motor symptom burdens and reduced quality of life. MHs have been called “minor,” but they have major clinical and prognostic implications and need early screening.

Efficacy of safinamide as add-on therapy after subthalamic nucleus deep brain stimulation in Parkinson disease.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective surgical treatment for advanced Parkinson's disease (PD). However, some patients still experience motor fluctuations or dyskinesia after STN-DBS. Safinamide is approved as add-on treatment to levodopa in fluctuating PD patients. In this study, we evaluated the effect of safinamide as adjunctive therapy in PD patients still experiencing motor fluctuations and dyskinesias after STN-DBS. PD patients treated for at least 2 years with bilateral STN-DBST and with troublesome motor fluctuation and/or dyskinesias were examined by means of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the quality of life questionnaire Parkinson's Disease Questionnaire-8 (PDQ-8) and the Non-Motor Symptoms Scale (NMSS) at baseline (T0), after 1 month of treatment with safinamide 50 mg daily (T1) and after another month of treatment with safinamide 100 mg daily (T2). Twenty-nine PD patients were examined. An improvement of the MDS-UPDRS IV score (motor complications) was observed between T0 and T1, T0 and T2, and T1 and T2. The time spent in the OFF state, the functional impact and the complexity of motor fluctuations significantly improved between T0 and T1 and T0 and T2. The mean levodopa equivalent daily dose significantly decreased from T0 to T1 and from T0 to T2. Regarding non-motor symptoms, an improvement on mood and pain was observed. Safinamide seems to be an effective adjunctive treatment in PD patients treated with bilateral STN-DBS, leading to an improvement of motor complications, mood and pain.

Longitudinal Prediction of Freezing of Gait in Parkinson's Disease: A Prospective Cohort Study.

Objective: Freezing of gait (FOG) is a disabling complication in Parkinson's disease (PD). Yet, studies on a validated model for the onset of FOG based on longitudinal observation are absent. This study aims to develop a risk prediction model to predict the probability of future onset of FOG from a multicenter cohort of Chinese patients with PD.Methods: A total of 350 patients with PD without FOG were prospectively monitored for ~2 years. Demographic and clinical data were investigated. The multivariable logistic regression analysis was conducted to develop a risk prediction model for FOG.Results: Overall, FOG was observed in 132 patients (37.70%) during the study period. At baseline, longer disease duration [odds ratio (OR) = 1.214, p = 0.008], higher total levodopa equivalent daily dose (LEDD) (OR = 1.440, p < 0.001), and higher severity of depressive symptoms (OR = 1.907, p = 0.028) were the strongest predictors of future onset of FOG in the final multivariable model. The model performed well in the development dataset (with a C-statistic = 0.820, 95% CI: 0.771–0.865), showed acceptable discrimination and calibration in internal validation, and remained stable in 5-fold cross-validation.Conclusion: A new prediction model that quantifies the risk of future onset of FOG has been developed. It is based on clinical variables that are readily available in clinical practice and could serve as a small tool for risk counseling.

Salivary ATP13A2 is a potential marker of therapy-induced motor complications and is expressed by inclusions in submandibulary glands in Parkinson ́s disease

BackgroundATP13A2 holds promise as biomarker for Parkinsońs disease (PD). No study has examined how salivary ATP13A2 is related to motor features in idiopathic PD. MethodsSalivary ATP13A2 concentration was evaluated with ELISA, and statistical correlations of ATP13A2 level with PD parameters were examined. The dose intensity of the dopaminergic medication regimen was expressed as levodopa equivalent daily dose (LEDD). ATP13A2 expression on histological sections of submandibular glands was evaluated using immunohistochemistry. ResultsSalivary ATP13A2 was undetectable in many subjects (28 % of patients, 43.7 % of controls). However, all the patients with motor complications (n = 28) showed quantifiable levels of ATP13A2, that positively correlated with MDS-UPDRS (total, parts III and IV), and LEDD (p < 0.05). Dyskinetic patients showed the highest LEDD values (p < 0.05). The histological study revealed: a) ATP13A2 staining was very intense in duct cells and vascular endothelium, and b) two patterns of ATP13A2-positive deposits are observed: rounded inclusions of 10–20 µm in diameter located in the interlobular tissue of the patients, and amorphous aggregates inside duct lumen in controls and patients. ConclusionsThe sensitivity of the ELISA assay was a major limitation for quantifying ATP13A2. However, salivary ATP13A2 was detected in all patients with motor complications, where a direct relationship among ATP13A2 concentration, levodopa equivalent daily dose, and MDS-UPDRS was found. Therefore, salivary ATP13A2 might be a reliable index of therapy-induced motor complications. ATP13A2 was expressed by rounded inclusions in the submandibulary gland of patients. This is the first description of ATP13A2-positive inclusions outside the nervous system.

Seborrheic Dermatitis Is Related to Motor Symptoms in Parkinson's Disease.

Parkinson's disease (PD) patients present with numerous motor and nonmotor symptoms. Seborrheic dermatitis (SD) is reported in 18.6%-59% of PD patients. However, the etiology of SD in PD patients remains unknown. The aim of this study was to determine how motor and nonmotor symptoms, age, sex, and levodopa-equivalent daily dose (LEDD) influence the appearance and severity of SD in PD patients, and then discuss about SD possible etiology based on the obtained results. Motor symptoms were evaluated using the Unified Parkinson's Disease Rating Scale part III and nonmotor symptoms were evaluated using the Parkinson's Disease Sleep Scale, Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction, and Non-Motor Symptoms Questionnaire. LEDD was calculated and demographic data on age, sex, disease duration, and symptoms of SD prior to a PD diagnosis were collected. A dermatologist evaluated the skin for SD using the Seborrhea Area and Severity Index. SD was present in 36.1% of the PD patients. There were positive correlations between age, motor-symptoms severity, and SD. After adjusting for age, disease duration, and sex, there remained a positive correlation between the severity of motor symptoms and SD. Patients with moderate-to-severe motor symptoms had more-severe SD symptoms, and their risk of developing SD was 1.8-fold higher. There was no correlation between SD and autonomic dysfunction, sleep disturbances, or other nonmotor symptoms, and no sex difference. In PD, SD is related to motor symptoms.

Correlation Between Lacunae and the Wearing-off Phenomenon in Parkinson's Disease.

PurposeLacunae are imaging biomarkers of cerebral small vessel disease (CSVD) and are correlated with the degree of gait instability in Parkinson’s disease (PD). The wearing-off phenomenon (WO) occurs more frequently in PD patients as disease progresses. The present study aimed to investigate the overall impact of the quantity and location of lacunae on the WO in PD.Patients and MethodsThis retrospective, single-center study included 315 consecutive eligible patients with PD from Beijing Tiantan Hospital from May 2016 to August 2018. We collected data on demographics and clinical features, assessed lacunae and examined the presence of the WO. The association between lacunae and the WO was assessed using a binary logistic regression model.ResultsThe number of lacunae was significantly associated with the WO in patients with PD according to a model adjusted for age at onset, disease duration, Hoehn–Yahr (H-Y) staging, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) total score and levodopa equivalent daily dosage (LEED) (P=0.037, OR 1.156, 95% CI 1.009, 1.325) and to a model further adjusted for other CSVD imaging biomarkers (P=0.046, OR 1.172, 95% CI 1.003, 1.369). Following additional adjustment for other potential confounders, the association remained significant (P=0.043, OR 1.195, 95% CI 1.005, 1.421). Lacunae in subcortical areas (P=0.004, OR 0.498, 95% CI 0.308, 0.803) and basal ganglia (P=0.046, OR 1.616, 95% CI 1.009, 2.587), especially in the caudate nuclei (P=0.023, OR 1.104, 95% CI 0.185, 0.881), were significantly associated with the WO in PD patients.ConclusionOur finding highlights the significant association between lacune and the WO, and lacunae may be an independent contributor to the WO in PD patients. Promoting neurovascular health may prevent the progression of the WO in PD patients.

Continuous subcutaneous apomorphine infusion in the early phase of advanced Parkinson’s disease: A prospective study of 22 patients

IntroductionParkinson’s disease (PD) patients usually start treatment with apomorphine infusion (APO) in later stages of advanced PD (aPD). This timing limits the evaluation of its motor efficacy and other potential clinical benefits throughout the full course of aPD. MethodsWe prospectively analyzed the effect of APO on motor and non-motor symptoms, cognitive function and quality of life (QoL) in 22 PD patients with early stage aPD, defined as: age < 71 years and diagnosis of aPD for < 3 years. ResultsAt baseline, mean (±SD) age and disease duration were 59.4 ± 6.1 and 8.7 ± 3.5 years, respectively. After 6 months of APO treatment, daily off-time decreased from 4.98 ± 2.37 to 1.48 ± 1.47 h (p ≤ 0.001) and UPDRS IV scores from 7.00 ± 2.58 to 5.32 ± 2.48 (p = 0.018). Dyskinesia did not worsen with APO despite an overall increase in levodopa equivalent daily dose. Mean NMSS scores improved with APO, from 52.50 ± 27.24 to 38.68 ± 27.17 (p = 0.002), with particular improvements in apathy and sleep quality. Mean PDQ-39 score was reduced with APO from 31.96 ± 11.93 to 19.27 ± 11.86 (p ≤ 0.001). Overall, cognition did not change after APO, while slight improvements were observed in executive functioning (attention and planning). All but one patient eventually underwent subthalamic deep brain stimulation. ConclusionIn patients with early stage initial aPD, s substantial benefit of APO was observed on motor symptoms, driven by a 70% reduction in off-time versus baseline, superior to that observed in previous prospective studies. APO also improved frontal dysfunction in PD patients.

Levodopa-induced dyskinesias in Parkinson's disease increase cerebrospinal fluid nitric oxide metabolites' levels.

Levodopa-induced dyskinesia (LID) is a common complication of Parkinson's disease (PD) therapy. Nitric oxide in the central nervous system may have a role in its pathophysiology. The present work investigates plasma and CSF levels of nitric oxide metabolites nitrite and nitrate in patients with PD, LID, and healthy control. We measured plasma and CSF nitrite and nitrate levels in patients with PD with and without LID and in healthy controls. The levels of plasma and CSF nitrite and nitrate were measured by ozone-based chemiluminescence. Sixty-seven participants were enrolled. CSF nitrite levels in patients with PD and LID were higher than in patients with PD without LID and healthy controls. CSF/plasma ratio of nitrite was higher in patients with PD and LID than in patients with PD without LID. The CSF/plasma ratio of nitrite in patients with PD and LID was higher than 1, indicating an intrathecal production of NO in patients with this motor complication. There was an increase in nitrate levels of CSF and CSF/plasma ratio of nitrate in patients with PD and LID compared to the healthy controls. Sex, age at evaluation, disease duration, and levodopa equivalent daily doses, as well as processing and storage time, did not critically influence these results. The present study demonstrated an increase in nitrite and nitrate levels in the central nervous system of patients with PD and LID. This finding strengthens the role of NO on LID pathophysiology.

Constructing Prediction Models for Freezing of Gait by Nomogram and Machine Learning: A Longitudinal Study.

Objectives: Although risk factors for freezing of gait (FOG) have been reported, there are still few prediction models based on cohorts that predict FOG. This 1-year longitudinal study was aimed to identify the clinical measurements closely linked with FOG in Chinese patients with Parkinson's disease (PD) and construct prediction models based on those clinical measurements using Cox regression and machine learning.Methods: The study enrolled 967 PD patients without FOG in the Hoehn and Yahr (H&Y) stage 1–3 at baseline. The development of FOG during follow-up was the end-point. Neurologists trained in movement disorders collected information from the patients on a PD medication regimen and their clinical characteristics. The cohort was assessed on the same clinical scales, and the baseline characteristics were recorded and compared. After the patients were divided into the training set and test set by the stratified random sampling method, prediction models were constructed using Cox regression and random forests (RF).Results: At the end of the study, 26.4% (255/967) of the patients suffered from FOG. Patients with FOG had significantly longer disease duration, greater age at baseline and H&Y stage, lower proportion in Tremor Dominant (TD) subtype, a higher proportion in wearing-off, levodopa equivalent daily dosage (LEDD), usage of L-Dopa and catechol-O-methyltransferase (COMT) inhibitors, a higher score in scales of Unified Parkinson's Disease Rate Scale (UPDRS), 39-item Parkinson's Disease Questionnaire (PDQ-39), Non-Motor Symptoms Scale (NMSS), Hamilton Depression Rating Scale (HDRS)-17, Parkinson's Fatigue Scale (PFS), rapid eye movement sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK), Epworth Sleepiness Scale (ESS), and a lower score in scales of Parkinson's Disease Sleep Scale (PDSS) (P < 0.05). The risk factors associated with FOG included PD onset not being under the age of 50 years, a lower degree of tremor symptom, impaired activities of daily living (ADL), UPDRS item 30 posture instability, unexplained weight loss, and a higher degree of fatigue. The concordance index (C-index) was 0.68 for the training set (for internal validation) and 0.71 for the test set (for external validation) of the nomogram prediction model, which showed a good predictive ability for patients in different survival times. The RF model also performed well, the C-index was 0.74 for the test set, and the AUC was 0.74.Conclusions: The study found some new risk factors associated with the FOG including a lower degree of tremor symptom, unexplained weight loss, and a higher degree of fatigue through a longitudinal study, and constructed relatively acceptable prediction models.

Prevalence and associated factors of malnutrition in patients with Parkinson's disease using CONUT and GNRI

ObjectiveParkinson's disease (PD) is a common neurodegenerative disease, but its nutritional problems have not received enough attention. This study aims to identify the prevalence and associated factors of malnutrition in PD patients using two simple nutritional tools. MethodsWe conducted a large-scale cross-sectional study with 1478 PD patients and equal healthy controls (HC). The controlling nutritional status score (CONUT) and geriatric nutritional risk index (GNRI) were used for malnutrition stratification. ResultsBy CONUT or GNRI, the prevalence of malnutrition in PD patients was higher than that in HC (40.7% vs. 25.3% and 11.1% vs. 2.1%, respectively). The binary logistic regression model showed that malnutrition in PD was associated with male sex (OR = 0.600, P < 0.001), older age (OR = 1.015, P = 0.003), lower body mass index (BMI) (OR = 0.942, P < 0.001), higher levodopa equivalent daily doses (LEDD) (OR = 1.001, P < 0.001), worse motor symptoms (OR = 1.012, P = 0.004), more serious perceptual problems/hallucinations (OR = 1.067, P = 0.019) by CONUT. In comparison, older age (OR = 1.045, P < 0.001), lower blood lymphocyte count (OR = 0.607, P = 0.006), lower serum total cholesterol levels (OR = 0.991, P < 0.001), dyskinesia (OR = 2.231, P = 0.002), worse motor symptoms (OR = 1.016, P = 0.015), more severe depression (OR = 1.028, P = 0.008) and perceptual problems/hallucinations (OR = 1.061, P = 0.033) were associated with malnutrition in PD by GNRI. ConclusionsOur study indicated that malnutrition is more prevalent in PD patients than HC. Multidimensional risk factors for malnutrition in PD should be taken seriously.

Cerebrovascular disease associated with Parkinson’s disease in Moldovan cohort study

Background: Parkinson’s disease (PD) is frequently associated with brain vascular lesions (BVLs), which may influence the severity of the disease. Material and methods: BVLs on MRI were determined in 78.4% of 111 consecutive PD patients (mean age 64.87 ± 7.69 y.o.; disease duration 50.21 ± 38.61 mo.; 48 women (43.2%), 63 men (56.8%)). Results: White matter lesions were present in 73 patients (p.) (65.77%): 61p. (54.95%) – deep white matter, 46p. (41.44%) – periventricular white matter, and 41p. (36.94%) – both locations. Lacunas were determined in 19p. (17.12%), cerebral fissures deepening – 52p. (46.85) %), perivascular spaces dilation – 34p. (30.63%), ventricular system dilation – 29p. (26.13%). Patients with and without BVLs had similar ages, ages at PD onset and disease duration. They had insignificantly higher Beck (7.26 ± 5.62 vs 6.86 ± 4.34), PDQ39 (Parkinson’s Disease Questionnaire) (59.71 ± 20.38 vs 51.94 ± 27.69) and NMS (Non-Motor Symptoms) (75.06 ± 45.21 vs 71.67 ± 26.35) scores; and lower MoCA (Montreal Cognitive Assessment) scores (21.92 ± 4.25 vs 22.38 ± 4.57). QRISK3 scores (19.68 ± 16.16 vs 12.90 ± 6.58) and levodopa equivalent daily dose (639.98 ± 223.05 vs. 439.69 ± 404.87) were significantly higher in patients with BVLs. Conclusions: Brain vascular lesions were common in our PD patients, and were associated with higher QRISK3 scores and higher levodopa equivalent daily dose, suggesting more disease severity

Clinical Efficacy and Dosing of Vibrotactile Coordinated Reset Stimulation in Motor and Non-motor Symptoms of Parkinson's Disease: A Study Protocol.

Enhanced neuronal synchronization of the subthalamic nucleus (STN) is commonly found in PD patients and corresponds to decreased motor ability. Coordinated reset (CR) was developed to decouple synchronized states causing long lasting desynchronization of neural networks. Vibrotactile CR stimulation (vCR) was developed as non-invasive therapeutic that delivers gentle vibrations to the fingertips. A previous study has shown that vCR can desynchronize abnormal brain rhythms within the sensorimotor cortex of PD patients, corresponding to sustained motor relief after 3 months of daily treatment. To further develop vCR, we created a protocol that has two phases. Study 1, a double blinded randomized sham-controlled study, is designed to address motor and non-motor symptoms, sensorimotor integration, and potential calibration methods. Study 2 examines dosing effects of vCR using a remote study design. In Study 1, we will perform a 7-month double-blind sham-controlled study including 30 PD patients randomly placed into an active vCR or inactive (sham) vCR condition. Patients will receive stimulation for 4 h a day in 2-h blocks for 6 months followed by a 1-month pause in stimulation to assess long lasting effects. Our primary outcome measure is the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III off medication after 6 months of treatment. Secondary measures include a freezing of gait (FOG) questionnaire, objective motor evaluations, sensorimotor electroencephalography (EEG) results, a vibratory temporal discrimination task (VTDT), non-motor symptom evaluations/tests such as sleep, smell, speech, quality of life measurements and Levodopa Equivalent Daily Dose (LEDD). Patients will be evaluated at baseline, 3, 6, and 7 months. In the second, unblinded study phase (Study 2), all patients will be given the option to receive active vCR stimulation at a reduced dose for an additional 6 months remotely. The remote MDS-UPDRS part III off medication will be our primary outcome measure. Secondary measures include sleep, quality of life, objective motor evaluations, FOG and LEDD. Patients will be evaluated in the same time periods as the first study. Results from this study will provide clinical efficacy of vCR and help validate our investigational vibrotactile device for the purpose of obtaining FDA clearance.Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04877015.

The role of frailty in Parkinson's disease: a cross-sectional study.

Frailty is an age-related state of increased risk for health-related adverse outcomes that reflects multisystem physiological changes and likely influences the clinical expression and disease progression of neurodegenerative disorders. The aim of the present study was to assess the potential relationship between frailty, as assessed by a frailty index (FI), and motor symptom severity, motor subtypes, and non-motor domains in Parkinson's disease (PD). We consecutively enrolled 150 PD patients. We administered an FI specifically designed for PD that included 50 age-related multidimensional biological deficits. Patients underwent a clinical assessment that evaluated motor and non-motor manifestations of PD. Using the FI score, we classified PD patients as relatively fit (FI ≤ 0.10), less fit (0.10 < FI ≤ 0.21), or frail (FI > 0.21). A linear regression model was designed to explore possible associations between frailty level and PD motor and non-motor manifestations. Frail patients showed greater motor symptom severity and motor complications than fitter patients. A trend towards a higher prevalence of the postural instability/gait disorder subtype was also observed in frail versus relatively fit and less fit patients. The global burden of non-motor symptoms was higher in frail patients. Increased frailty was associated with more severe motor and non-motor symptoms, as well as with more pronounced cognitive deficits. These associations remained significant even when "traditional" predictors of PD severity (age, disease duration, and levodopa equivalent daily dose) were considered. The present findings indicate that the FI is associated with both motor and non-motor features of PD.

Single‐Center Study of 103 Consecutive Parkinson's Disease Patients with Levodopa‐Carbidopa Intestinal Gel

Levodopa-carbidopa intestinal gel (LCIG) effectively reduces off time and dyskinesia and increases on time in advanced Parkinson's disease (PD). However, patients with LCIG-infusion experience frequent complications and some discontinue treatment early on. The objectives of this study were to find predictive factors for early dropout from the LCIG infusion, analyze the treatment burden on the tertiary health care system, and explore changes in medication during the LCIG treatment. LCIG-infusion was administrated to 103 patients between July 2006 and May 2020 at the Helsinki University Hospital, accumulating 350 years of follow-up data. We evaluated, retrospectively, changes in medication during treatment, discontinuation of the infusion, and adverse events from the patient records. Living alone was a predictive factor for early dropout (OR=3.88; 95% CI=1.03-14.66; P=0.045). The treatment burden on the tertiary health care system increased after the initiation of LCIG infusion mostly because of common complications related to the infusion system (median change of in- and out-patient visits +1, P=0.03). Mean levodopa equivalent daily dose (LEDD) rose from baseline to 6 months (1246.7 vs. 1684.9, P=0.001) and stabilized thereafter. Patients commonly switched from "polypharmacy" to "LCIG-only" or "LCIG + oral levodopa" medication-groups during long-term treatment. Recurrent complications related to the infusion system increase the treatment burden on tertiary healthcare system after the initiation of LCIG-infusion. Most patients continue long-term with the infusion. Few patients discontinue infusion during the first year after initiation and living alone appears to be a risk factor for this outcome.

Striatal dopamine transporter availability and individual clinical course within the 1-year follow-up of deep brain stimulation of the subthalamic nucleus in patients with Parkinson's disease.

Degeneration of dopaminergic neurons in the substantia nigra projecting to the striatum is responsible for the motor symptoms in Parkinson's disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established procedure to alleviate these symptoms in advanced PD. Yet the mechanism of action, especially the effects of STN-DBS on the availability of striatal dopamine transporter (DAT) as a marker of nigrostriatal nerve cell function, remains largely unknown. The aim of this study was therefore to evaluate whether 1) DAT availability changes within 1 year of STN-DBS and 2) the clinical outcome can be predicted based on preoperative DAT availability. Twenty-seven PD patients (mean age 62.7 ± 8.9 years; mean duration of illness 13.0 ± 4.9 years; PD subtypes: akinetic-rigid, n = 11; equivalence, n = 13; and tremor-dominant, n = 3) underwent [123I]FP-CIT SPECT preoperatively and after 1 year of STN-DBS. DAT availability as determined by the specific binding ratio (SBR) was assessed by volume of interest (VOI) analysis of the caudate nucleus and the putamen ipsilateral and contralateral to the clinically more affected side. Unified Parkinson's Disease Rating Scale (UPDRS) III scores improved significantly (mean preoperative on medication 25.6 ± 12.3, preoperative off medication 42.3 ± 15.2, postoperative on medication/off stimulation 41.4 ± 13.2, and postoperative on medication/on stimulation 16.1 ± 9.4; preoperative on medication vs postoperative on medication/on stimulation, p = 0.006), while the levodopa-equivalent daily dose was reduced (mean preoperative 957 ± 440 mg vs postoperative 313 ± 189 mg, p < 0.001). The SBR did not differ significantly before and 1 year after DBS, regardless of PD subtype. Preoperative DAT availability was not related to the change in UPDRS III score, but the change in DAT availability was significantly correlated with the change in UPDRS III score (contralateral head of the caudate VOI, p = 0.014; contralateral putamen VOI, p = 0.018). Overall, DAT availability did not change significantly after 1 year of STN-DBS. However, on an individual basis, the improvement in UPDRS III score was associated with an increase in DAT availability, whereas DAT availability before STN-DBS surgery did not predict the clinical outcome. Whether a subtype-specific pattern of preoperative DAT availability can become a reliable predictor of successful STN-DBS must be evaluated in larger study cohorts.

Age at Parkinson's disease onset modulates the effect of levodopa on response inhibition: Support for the dopamine overdose hypothesis from the antisaccade task

The antisaccade task is an established eye-tracking paradigm to explore response inhibition. While many studies showed that antisaccade performance is impaired in Parkinson's disease (PD), the effect of dopaminergic medication is still an area of debate. According to the dopamine overdose hypothesis, intrinsic basal dopamine levels in ventral parts of the striatum determine whether levodopa intake has beneficial or detrimental effects on dopamine-dependent cognitive tasks. The objective of this study was therefore to explore the effect of several disease-related factors on changes in antisaccade performance after levodopa intake in PD. Thirty-five individuals with PD (and 30 healthy controls) performed antisaccades in OFF and ON medication state. Multiple linear regressions were calculated to predict the change in antisaccade latency, directive errors and express saccade rate based on age at PD onset, disease duration, levodopa-equivalent daily dose, motor symptom severity and executive functions.Levodopa intake did not alter antisaccade performance on a group level. However, the effect of levodopa was differentially modulated by age at PD onset and motor symptom severity. Earlier disease onset and milder motor symptoms in OFF medication state were associated with reduced response inhibition capacity after levodopa intake measured as increased express saccade and error rates.Our results indicate that levodopa may have opposing effects on oculomotor response inhibition dependent on the age at PD onset and motor disease severity. Assuming less dopaminergic loss in ventral parts of the striatum in early compared to late onset PD, these findings support the dopamine overdose hypothesis.

Choroidal Thickness Correlates with Clinical and Imaging Metrics of Parkinson's Disease: A Pilot Study.

Parkinson's disease (PD) is marked clinically by motor symptoms and pathologically by Lewy bodies and dopamine neuron loss in the substantia nigra pars compacta (SNc). Higher iron accumulation, assessed by susceptibility MRI, also is observed as PD progresses. Recently, evidence has suggested that PD affects the retina. To better understand retinal alterations in PD and their association to clinical and SNc iron-related imaging metrics. Ten PD and 12 control participants (2 eyes each) from an ongoing PD imaging biomarker study underwent enhanced depth imaging optical coherence tomography evaluation. Choroidal (vascular) thickness and nerve layers were measured in 4 subregions [superior, temporal, inferior, and nasal] and at 3 foveal distances (1, 1.5, and 3 mm). These metrics were compared between PD and control groups. For significantly different metrics, their associations with clinical [levodopa equivalent daily dosage (LEDD), motor and visuospatial function] and SNc susceptibility MRI metrics [R2* and quantitative susceptibility mapping (QSM)] were explored. Compared to control participants, PD participants had a thicker choroid (p = 0.005), but no changes in nerve layers. Higher mean choroidal thickness was associated with lower LEDD (p < 0.01) and better visuospatial function (p < 0.05). Subregion analyses revealed higher choroidal thickness correlated with lower LEDD and better motor and visuospatial measures. Higher mean choroidal thickness also was associated with lower nigral iron MRI (p < 0.05). A small cohort of PD research participants displayed higher choroidal thickness that was related to better clinical performance and less nigral pathology. These intriguing findings warrant further investigation.

Neuropsychiatric Burden Is a Predictor of Early Freezing and Motor Progression in Drug-Naïve Parkinson's Disease.

Neuropsychiatric symptoms (NPS) are the most common non-motor symptom in Parkinson's disease (PD). To investigate the association between the burden of NPS and motor prognosis in patients with PD. We enrolled 329 drug-naïve patients with PD, who was non-demented and followed-up≥2 years after their first visit to the clinic with baseline dopamine transporter (DAT) imaging and neuropsychiatric inventory (NPI) scores. We performed a survival analysis and a linear mixed model analysis to assess longitudinal motor outcomes according to the NPI total score. The Kaplan-Meier analysis showed no difference in the development of levodopa-induced dyskinesia and wearing-off according to the NPI total score. However, higher burden of NPI total score was associated with earlier freezing of gait (FOG) development in the time-dependent Cox regression models after adjusting for age at symptom onset, sex, disease duration, Unified PD Rating Scale motor score, baseline Mini-Mental State Examination score, DAT activity in the posterior putamen and levodopa-equivalent daily dose (LEDD) (Hazard ratio 1.047, p = 0.002). A linear mixed model analysis revealed that patients with a higher NPI total score had a more rapid LEDD increment (NPI×time, p = 0.003). Among 52 patients with PD who eventually developed FOG during the follow-up period, there was a significant correlation between the NPI total score and time with FOG development (γ= -0.472; p = 0.001) after adjusting for confounding factors. The present study demonstrated that the severity of NPS is a predictor of early freezing and motor progression in patients with PD.

A Cross-Sectional Comprehensive Assessment of the Profile and Burden of Non-motor Symptoms in Relation to Motor Phenotype in the Nigeria Parkinson Disease Registry Cohort.

Data on non-motor symptoms (NMS) in black Africans with Parkinson's disease (PD) are sparse. To describe the profile of NMS in the Nigeria PD Registry (NPDR) cohort and explore the relationship between NMS and PD motor phenotype. We conducted a cross-sectional study of the frequency and burden of NMS, based on the non-motor symptoms scale (NMSS) and the Chaudhuri method respectively in our cohort. Baseline demographics, disease characteristics (Hoehn and Yahr stage, MDS-UPDRS total score and Part III motor score), motor phenotype (based on Stebbin et al's algorithm), and levodopa equivalent daily dose (LEDD) were documented. Data are presented for 825 PD whose mean age at study was 63.7 ± 10.1 years, female sex-221 [26.8%] while median PD duration was 36 months. PD phenotypes included tremor-dominant 466 (56.5%), postural instability and gait disorder (PIGD) 259 (31.4%), and indeterminate 100 (12.1%). 82.6% were on treatment (median LEDD of 500 mg/24 hours). 804 (97.5%) endorsed at least 1 NMS. The median NMSS score was 26.0 while subscores for urinary and sexual function domains were significantly higher in males (P< 0.05). PIGD-PD had more frequent NMS and higher frequency of severe/very severe NMSS burden (P= 0.000 for both). Nocturia and fatigue were the most prevalent NMS overall and across motor subtypes. PIGD phenotype and total UPDRS scores were the independent determinants of NMSS scores (P= 0.000). The profile and burden of NMS, and association with motor subtype in our black African cohort is largely similar to descriptions from other populations.