INTRODUCTION:
Essential Tremor (ET) treatment is focused on medical management of motor symptoms and includes pharmacotherapy and ventral intermediate nucleus (VIM) thalamotomy, which is being ...largely replaced by thalamic Deep Brain Stimulation (DBS) as the surgical treatment of choice. DBS of the VIM thalamus is recommended as a therapeutic option for appropriate subjects with ET (Elble RJ., et al. Expert Rev Neurother. 2018).
METHODS:
This is a prospective, on-label, multi-center, international DBS outcomes study conducted at up to 50 implanting centers. All participants are implanted with a multiple-source, constant-current directional DBS system (Vercise, Boston Scientific). Subjects are followed for up to 3-years post implantation where their overall improvement in quality of life and ET symptoms are evaluated. Clinical endpoints evaluated at baseline and follow-up timepoints include: The Essential Tremor Rating Assessment Scale (TETRAS), Quality of Life in Essential Tremor Questionnaire (QUEST), Fahn-Tolosa-Marin Rating Scale (TRS), and Global Impression of Change. Adverse events also collected.
RESULTS:
To date, 18-implanted subjects with a mean disease duration of 15.1 ± 14.6-years and a baseline QUEST Summary Index score of 35.0 ± 12.4. At 6-months post-DBS, a clinically significant improvement in quality of life (∆ = 19.5-point change in QUEST SI score) was reported. In addition, a mean 9-hours of tremor reduction was noted (14-hours at Baseline, 6.9-hours at 6-months) in a typical day at 6-months. All subjects (100%) reported mild disability, and no subject reported moderate or marked disability (89% at baseline) as reported by TRS at 6 months.
CONCLUSIONS:
This work represents the first comprehensive, large scale collection of real-world outcomes and evaluation of safety and effectiveness of a multiple-source, constant-current DBS system capable of providing directionality for use in treatment of Essential Tremor.
The NF-κB pathway is involved in the pathogenesis of neurological disorders that have inflammation as a hallmark, including Parkinson’s disease (PD). Our objective was to determine whether common ...functional variants in the
NFKB1, NFKBIA
and
NFKBIZ
genes were associated with the risk of PD. A total of 532 Spanish PD cases (61% male; 38% early-onset, ≤ 55 years) and 300 population controls (50% ≤55 years) were genotyped for the
NFKB1
rs28362491 and rs7667496,
NFKBIA
rs696, and
NFKBIZ
rs1398608 polymorphisms. We compared allele and genotype frequencies between early and late-onset, male and female, and patient’s vs. controls. We found that the two
NFKB1
alleles were significantly associated with PD in our population (
p
= 0.01; total patients vs. controls), without difference between Early and Late onset patients. The frequencies of the
NFKB1
variants significantly differ between male and female patients. Compared to controls, male patients showed a significantly higher frequency of rs28362491 II (
p
= 0.02, OR = 1.52, 95%CI = 1.10–2.08) and rs28362491 C (
p
= 0.003, OR = 1.62, 95%CI = 1.18–2.22). The two
NFKB1
variants were in strong linkage disequilibrium and the I-C haplotype was significantly associated with the risk of PD among male (
p
= 0.002). In conclusion, common variants in the NF-kB genes were associated with the risk of developing PD in our population, with significant differences between male and female. These results encourage further studies to determine the involvement of the NF-kB components in the pathogenesis of Parkinson´s disease.
Background and purpose
The objective of this study was to analyze the relationship between motor complications and non‐motor symptom (NMS) burden in a population of patients with Parkinson’s disease ...(PD) and also in a subgroup of patients with early PD.
Methods
Patients with PD from the COPPADIS cohort were included in this cross‐sectional study. NMS burden was defined according to the Non‐Motor Symptoms Scale (NMSS) total score. Unified Parkinson’s Disease Rating Scale (UPDRS) part IV was used to establish motor complication types and their severity. Patients with ≤5 years of symptoms from onset were included as patients with early PD.
Results
Of 690 patients with PD (62.6 ± 8.9 years old, 60.1% males), 33.9% and 18.1% presented motor fluctuations and dyskinesia, respectively. The NMS total score was higher in patients with motor fluctuations (59.2 ± 43.1 vs. 38.3 ± 33.1; P < 0.0001) and dyskinesia (63.5 ± 40.7 vs. 41.4 ± 36.3; P < 0.0001). In a multiple linear regression model and after adjustment for age, sex, disease duration, Hoehn & Yahr stage, UPDRS‐III score and levodopa equivalent daily dose, UPDRS‐IV score was significantly related to a higher NMSS total score (β = 0.27; 95% confidence intervals, 2.81–5.61; P < 0.0001), as it was in a logistic regression model on dichotomous NMSS total score (≤40, mild or moderate vs. >40, severe or very severe) (odds ratio, 1.31; 95% confidence intervals, 1.17–1.47; P < 0.0001). In the subgroup of patients with early PD (n = 396; mean disease duration 2.7 ± 1.5 years), motor fluctuations were frequent (18.1%) and similar results were obtained.
Conclusions
Motor complications were frequent and were associated with a greater NMS burden in patients with PD even during the first 5 years of disease duration.
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.
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.
Quality of life (QOL) plays an important role in independent living in Parkinson's disease (PD) patients, being crucial to know what factors impact QoL throughout the course of the disease. Here we ...identified predictors of QoL impairment in PD patients from a Spanish cohort. PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016, to November 2017, were followed up during 2 years. Health-related QoL (HRQoL) and global QoL (GQoL) were assessed with the 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8), respectively, at baseline (V0) and at 24 months ± 1 month (V2). Clinically significant QoL impairment was defined as presenting an increase (PDQ-39SI) or decrement (EUROHIS-QOL8) at V2 ≥ 10% of the score at baseline (V0). A comparison with a control group was conducted for GQoL. GQoL did not change significantly in PD patients (N = 507; p = 0.686) or in the control group (N = 119; p = 0.192). The mean PDQ-39SI was significantly increased in PD patients (62.7 ± 8.5 years old; 58.8% males; N = 500) by 21.6% (from 16.7 ± 13 to 20.3 ± 16.4; p < 0.0001) at V2. Ninety-three patients (18.6%) presented a clinically significant HRQoL impairment at V2. To be younger (OR = 0.896; 95% CI 0.829-0.968; p = 0.006), to be a female (OR = 4.181; 95% CI 1.422-12.290; p = 0.009), and to have a greater increase in BDI-II (Beck Depression Inventory-II) (OR = 1.139; 95% CI 1.053-1.231; p = 0.001) and NMSS (Non-Motor Symptoms Scale) (OR = 1.052; 95% CI 1.027-1.113; p < 0.0001) total scores from V0 to V2 were associated with clinically significant HRQoL impairment at the 2-year follow-up (Hosmer-Lemeshow test, p = 0.665; R
= 0.655). An increase in ≥5 and ≥10 points of BDI-II and NMSS total score at V2 multiplied the probability of presenting clinically significant HRQoL impairment by 5 (OR = 5.453; 95% CI 1.663-17.876; p = 0.005) and 8 (OR = 8.217; 95% CI, 2.975-22.696; p = 0.002), respectively. In conclusion, age, gender, mood, and non-motor impairment were associated with clinically significant HRQoL impairment after the 2-year follow-up in PD patients.
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.