A good response to levodopa is a key factor to indicate device-aided therapies in people with Parkinson's disease (PwPD). The aim of the present study was to analyze the response to levodopa in PwPD ...with motor fluctuations followed for 4 years.
PwPD with motor fluctuations recruited from January 2016 to November 2017 from the COPPADIS cohort and assessed annually (from baseline to 4-year follow-up) during the OFF and ON states were included in this analysis. At each visit, the Unified Parkinson's Disease Rating Scale – part III (UPDRS-III) was applied during the OFF state (without medication during the last 12 h) and during the ON state. General linear model repeated measures were used to test for changes in the mean UPDRS–III–OFF, UPDRS–III–ON, and ΔUPDRS-III (UPDRS–III–OFF – UPDRS–III–ON) between visits. Levodopa equivalent daily dose (LEDD) was included as covariate.
Sixty-three patients (63.94 ± 8.42 years old; 68.3% males) were included. Mean disease duration was 7.81 ± 3.64 years. From baseline to 4-year follow-up visit, a significant increase in both the UPDRS–III–OFF (from 27.98 ± 9.58 to 31.75 ± 12.39; p = 0.003) and the UPDRS–III–ON (from 15.92 ± 7.93 to 18.84 ± 8.17; p = 0.006) was observed despite the significant increase in the LEDD (from 896.35 ± 355.65 to 1085.51 ± 488.29; p = 0.003). However, no significant differences were detected between visits in the ΔUPDRS-III.
In this cohort of PwPD with motor fluctuations, the response to levodopa did not weaken after a 4-year follow-up.
•A good response to levodopa is a key factor to indicate device-aided or on-demand therapies in Parkinson's disease.•Response to levodopa did not weaken after a 4-year follow-up in 63 fluctuators PD patients.•On and off scores worsen at the expense of axial symptoms and in parallel with conservation of the levodopa response.•There were no differences by motor phenotype.
ABSTRACT
Background
Dopamine replacement therapy reduces most motor and nonmotor features of Parkinson's disease. However, with disease progression, adjustments of dopaminergics and the application ...of advanced therapies must be considered.
Objectives
To validate the OPTIMIPARK questionnaire as a tool to help clinicians make therapeutic decisions on patients treated with levodopa.
Methods
We tested a questionnaire including 9 items encompassing motor and nonmotor signs, complications, and disability in a multicenter, observational, cross‐sectional study. A neurologist (neurologist 1 N1) assessed patients according to regular clinical practice and blinded to the OPTIMIPARK questionnaire score. Therapeutic decisions were classified as “no changes,” “adjustment of conventional treatment,” and “advanced therapy indicated.” External neurologists (neurologist 3 N3 and neurologist 4 N4), who only knew the patient age, years of disease, and current treatment, made their therapeutic decisions based on the OPTIMIPARK score. Concordance between the criterion of the N1 versus the OPTIMIPARK‐based N3–N4 consensus was analyzed applying weighted κ. The area under Receiving Operating Characteristic (ROC) curves was calculated for OPTIMIPARK scores.
Results
A total of 113 patients with Parkinson's disease were included. The OPTIMIPARK‐based decision led to a higher proportion of patients requiring therapeutic modification than N1 assessment (74% vs. 60%; P = 0.002). Concordance between the N1 and N3–N4 decisions was moderate, whereas interobserver agreement among N3 and N4 was high. Area Under the Curve(AUC) values of 0.83 and 0.82 were found for “no changes” and “advanced therapy indicated” decisions by the N1 neurologist.
Conclusions
OPTIMIPARK might be more sensitive than regular clinical practice in suggesting the need for a therapeutic change. Furthermore, the low and high scores identify with high accuracy well‐adjusted patients and candidates for advanced therapy, respectively.
Camptocormia is an involuntary flexion between 15-45° of the thoracolumbar spine when standing, walking or sitting, which disappears completely in the supine position. Is associated to Parkinson's ...disease and other neurodegenerative conditions, being its physiopatology unknown. We report three cases of atypical anti-psychotic induced camptocormia.
Visual hallucinations (VH) and subjective cognitive complaints (SCC) are associated with cognitive impairment (CI) in Parkinson's disease. Our aims were to determine the association between VH and ...SCC and the risk of CI development in a cohort of patients with Parkinson's disease and normal cognition (PD-NC).
Patients with PD-NC (total score of >80 on the Parkinson's Disease Cognitive Rating Scale PD-CRS) recruited from the Spanish COPPADIS cohort from January 2016 to November 2017 were followed up after 2 years. Subjects with a score of ≥1 on domain 5 and item 13 of the Non-Motor Symptoms Scale at baseline (V0) were considered as "with SCC" and "with VH," respectively. CI at the 2-year follow-up (plus or minus 1 month) (V2) was defined as a PD-CRS total score of <81.
At V0 (
=376, 58.2% males, age 61.14±8.73 years mean±SD), the frequencies of VH and SCC were 13.6% and 62.2%, respectively. VH were more frequent in patients with SCC than in those without: 18.8% (44/234) vs 4.9% (7/142),
<0.0001. At V2, 15.2% (57/376) of the patients had developed CI. VH presenting at V0 was associated with a higher risk of CI at V2 (odds ratio OR=2.68, 95% confidence interval=1.05-6.83,
=0.0.039) after controlling for the effects of age, disease duration, education, medication, motor and nonmotor status, mood, and PD-CRS total score at V0. Although SCC were not associated with CI at V2, presenting both VH and SCC at V0 increased the probability of having CI at V2 (OR=3.71, 95% confidence interval=1.36-10.17,
=0.011).
VH were associated with the development of SCC and CI at the 2-year follow-up in patients with PD-NC.
Background and objective
Recently, we demonstrated that staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on four axes (motor, non‐motor, cognition, and ...dependency) and five stages, correlated with disease severity and patients’ quality of life. Here, we analyzed the correlation of MNCD staging with PD caregiver's status.
Patients and methods
Data from the baseline visit of PD patients and their principal caregiver recruited from 35 centers in Spain from the COPPADIS cohort from January 2016 to November 2017 were used to apply the MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) in this cross‐sectional analysis. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory‐II (BDI‐II), PQ‐10, and EUROHIS‐QOL 8‐item index (EUROHIS‐QOL8).
Results
Two hundred and twenty‐four PD patients (63 ± 9.6 years old; 61.2% males) and their caregivers (58.5 ± 12.1 years old; 67.9% females) were included. The frequency of MNCD stages was 1, 7.6%; 2, 58.9%; 3, 31.3%; and 4–5, 2.2%. A more advanced MNCD stage was associated with a higher score on the ZCBI (p < .0001) and CSI (p < .0001), and a lower score on the PQ‐10 (p = .001), but no significant differences were observed in the BDI‐II (p = .310) and EUROHIS‐QOL8 (p = .133). Moderate correlations were observed between the MNCD total score and the ZCBI (r = .496; p < .0001), CSI (r = .433; p < .0001), and BDI‐II (r = .306; p < .0001) in caregivers.
Conclusion
Staging PD according to the MNCD classification is correlated with caregivers’ strain and burden.
Recently, it has been reported that staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on 4 axes (Motor; Non‐motor; Cognition; Dependency) and 5 stages, correlated with disease severity and patients' quality of life. In this new manuscript, we observed that staging PD according to the MNCD classification correlated with caregivers' strain and burden.
Introduction. Drooling in Parkinson’s disease (PD) is frequent but often goes underrecognized. Our aim was to examine the prevalence of drooling in a PD cohort and compare it with a control group. ...Specifically, we identified factors associated with drooling and conducted subanalyses in a subgroup of very early PD patients. Patients and Methods. PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30-day follow-up (V2) from 35 centers in Spain from the COPPADIS cohort were included in this longitudinal prospective study. Subjects were classified as with or without drooling according to item 19 of the NMSS (Nonmotor Symptoms Scale) at V0, V1 (1-year ± 15 days), and V2 for patients and at V0 and V2 for controls. Results. The frequency of drooling in PD patients was 40.1% (277/691) at V0 (2.4% (5/201) in controls; p < 0.0001), 43.7% (264/604) at V1, and 48.2% (242/502) at V2 (3.2% (4/124) in controls; p < 0.0001), with a period prevalence of 63.6% (306/481). Being older (OR = 1.032; p = 0.012), being male (OR = 2.333; p < 0.0001), having greater nonmotor symptom (NMS) burden at the baseline (NMSS total score at V0; OR = 1.020; p < 0.0001), and having a greater increase in the NMS burden from V0 to V2 (change in the NMSS total score from V0 to V2; OR = 1.012; p < 0.0001) were identified as independent predictors of drooling after the 2-year follow-up. Similar results were observed in the group of patients with ≤2 years since symptom onset, with a cumulative prevalence of 64.6% and a higher score on the UPDRS-III at V0 (OR = 1.121; p = 0.007) as a predictor of drooling at V2. Conclusion. Drooling is frequent in PD patients even at the initial onset of the disease and is associated with a greater motor severity and NMS burden.
For specialists in charge of Parkinson's disease (PD), one of the most time-consuming tasks of the consultations is the assessment of symptoms and motor fluctuations. This task is complex and is ...usually based on the information provided by the patients themselves, which in most cases is complex and biased. In recent times, different tools have appeared on the market that allow automatic ambulatory monitoring. The MoMoPa-EC clinical trial (NCT04176302) investigates the effect of one of these tools-Sense4Care's STAT-ON-can have on routine clinical practice. In this sub-analysis the agreement between the Hauser diaries and the STAT-ON sensor is analyzed.
Eighty four patients from MoMoPa-EC cohort were included in this sub-analysis. The intraclass correlation coefficient was calculated between the patient diary entries and the sensor data.
The intraclass correlation coefficient of both methods was 0.57 (95% CI: 0.3-0.73) for the OFF time (%), 0.48 (95% CI: 0.17-0.68) for the time in ON (%), and 0.65 (95% CI%: 0.44-0.78) for the time with dyskinesias (%). Furthermore, the Spearman correlations with the UPDRS scale have been analyzed for different parameters of the two methods. The maximum correlation found was -0.63 (
< 0.001) between Mean Fluidity (one of the variables offered by the STAT-dON) and factor 1 of the UPDRS.
This sub-analysis shows a moderate concordance between the two tools, it is clearly appreciated that the correlation between the different UPDRS indices is better with the STAT-ON than with the Hauser diary.
https://clinicaltrials.gov/show/NCT04176302 (NCT04176302).
Sex plays a role in Parkinson's disease (PD) mechanisms. We analyzed sex difference manifestations among Spanish patients with PD.
PD patients who were recruited from the Spanish cohort COPPADIS from ...January 2016 to November 2017 were included. A cross-sectional and a two-year follow-up analysis were conducted. Univariate analyses and general linear model repeated measure were used.
At baseline, data from 681 PD patients (mean age 62.54 ± 8.93) fit the criteria for analysis. Of them, 410 (60.2%) were males and 271 (39.8%) females. There were no differences between the groups in mean age (62.36 ± 8.73 vs. 62.8 ± 9.24;
= 0.297) or in the time from symptoms onset (5.66 ± 4.65 vs. 5.21 ± 4.11;
= 0.259). Symptoms such as depression (
< 0.0001), fatigue (
< 0.0001), and pain (
< 0.00001) were more frequent and/or severe in females, whereas other symptoms such as hypomimia (
< 0.0001), speech problems (
< 0.0001), rigidity (
< 0.0001), and hypersexuality (
< 0.0001) were more noted in males. Women received a lower levodopa equivalent daily dose (
= 0.002). Perception of quality of life was generally worse in females (PDQ-39,
= 0.002; EUROHIS-QOL8,
= 0.009). After the two-year follow-up, the NMS burden (Non-Motor Symptoms Scale total score) increased more significantly in males (
= 0.012) but the functional capacity (Schwab and England Activities of Daily Living Scale) was more impaired in females (
= 0.001).
The present study demonstrates that there are important sex differences in PD. Long-term prospective comparative studies are needed.
The management of motor fluctuations in Parkinson's disease (PD) can be challenging, and current therapeutic options include the use of monoamine oxidase B inhibitors (MAO-B inhibitors), among ...others. The aim of this study was to evaluate the effectiveness and safety of safinamide in the clinical practice carried out in the Toledo Movement Disorders Unit.
This is a retrospective study in which data were collected at baseline and at six months from PD patients who were started on safinamide as an add-on therapy with a stable dose of levodopa in line with standard clinical practice. An analysis was performed by subgroups: patients who were given low-dose safinamide and patients who previously received rasagiline.
Ninety patients (47 previously received rasagiline) completed the six-month follow-up. A statistically significant decrease in morning akinesia, nocturnal akinesia, wearing off, unpredictable off phenomenon and Unified Parkinson's Disease Rating Scale-III was observed both in those who previously received rasagiline and in those treated with low doses of safinamide. No variation was found in the dyskinesias. The adverse events described were mild, with generalised weakness, dizziness, nausea, headache and alopecia.
Safinamide has been shown to be effective and safe in improving motor fluctuations, motor symptoms and the subjective perception of disease severity in PD patients previously receiving rasagiline and in those receiving low-dose safinamide, all of which is accompanied by a good safety profile.
The aim of this study was to compare the progression of independence in activities of daily living (ADL) in Parkinson's disease (PD) patients versus a control group, as well as to identify predictors ...of disability progression and functional dependency (FD).
PD patients and control subjects, who were recruited from 35 centers of Spain from the COPPADIS cohort between January 2016 and November 2017 (V0), were included. Patients and subjects were then evaluated again at the 2-year follow-up (V2). Disability was assessed with the Schwab & England Activities of Daily Living Scale (S&E-ADLS) at V0 and V2. FD was defined as an S&E-ADLS score less than 80%.
In the PD group, a significant decrease in the S&E-ADLS score from V0 to V2 (N = 507; from 88.58 ± 10.19 to 84.26 ± 13.38;
< 0.0001; Cohen's effect size = -0.519) was observed but not in controls (N = 124; from 98.87 ± 6.52 to 99.52 ± 2.15;
= 0.238). When only patients considered functional independent at baseline were included, 55 out of 463 (11.9%) converted to functional dependent at V2. To be a female (OR = 2.908;
= 0.009), have longer disease duration (OR = 1.152;
= 0.002), have a non-tremoric motor phenotype at baseline (OR = 3.574;
= 0.004), have a higher score at baseline in FOGQ (OR = 1.244;
< 0.0001) and BDI-II (OR = 1.080;
= 0.008), have a lower score at baseline in PD-CRS (OR = 0.963;
= 0.008), and have a greater increase in the score from V0 to V2 in UPDRS-IV (OR = 1.168;
= 0.0.29), FOGQ (OR = 1.348;
< 0.0001) and VAFS-Mental (OR = 1.177;
= 0.013) (adjusted R-squared 0.52; Hosmer and Lemeshow test = 0.94) were all found to be independent predictors of FD at V2.
In conclusion, autonomy for ADL worsens in PD patients compared to controls. Cognitive impairment, gait problems, fatigue, depressive symptoms, more advanced disease, and a non-tremor phenotype are independent predictors of FD in the short-term.
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