Diplopia Is Frequent and Associated with Motor and Non-Motor Severity in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up

Background and objective: Diplopia is relatively common in Parkinson’s disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it. 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 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as “with diplopia” or “without diplopia” according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year ± 15 days), and V2 for the patients and at V0 and V2 for the controls. Results: The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269–4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012–1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson’s Disease Rating Scale–III (OR = 1.039; 95%CI, 1.023–1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001–1.057; p = 0.049) scores were independent factors associated with diplopia (R2 = 0.25; Hosmer and Lemeshow test, p = 0.716). Conclusions: Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity.

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Constipation Predicts Cognitive Decline in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-up and Comparison with a Control Group

Journal of Parkinson s Disease ◽

10.3233/jpd-212868 ◽

2021 ◽

pp. 1-17

Author(s):

Diego Santos García ◽

Lucía García Roca ◽

Teresa de Deus Fonticoba ◽

Carlos Cores Bartolomé ◽

Lucía Naya Ríos ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Cognitive Decline ◽

Rating Scale ◽

Cognitive Status ◽

Control Group ◽

Cognitive Changes ◽

Non Motor Symptoms

Background: Constipation has been linked to cognitive impairment development in Parkinson’s disease (PD). Objective: Our aim was to analyze cognitive changes observed in PD patients and controls from a Spanish cohort with regards to the presence or not of constipation. Methods: PD patients and controls recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were followed-up during 2 years. The change in cognitive status from baseline (V0) to 2-year follow-up was assessed with the PD-CRS (Parkinson’s Disease Cognitive Rating Scale). Subjects with a score ≥1 on item 21 of the NMSS (Non-Motor Symptoms Scale) at baseline (V0) were considered as “with constipation”. Regression analyses were applied for determining the contribution of constipation in cognitive changes. Results: At V0, 39.7% (198/499) of PD patients presented constipation compared to 11.4% of controls (14/123) (p < 0.0001). No change was observed in cognitive status (PD-CRS total score) neither in controls without constipation (from 100.24±13.72 to 100.27±13.68; p = 0.971) and with constipation (from 94.71±10.96 to 93.93±13.03; p = 0.615). The PD-CRS total score decreased significantly in PD patients with constipation (from 89.14±15.36 to 85.97±18.09; p < 0.0001; Coehn’s effect = –0.35) compared to patients without constipation (from 93.92±15.58 to 93.14±17.52; p = 0.250) (p = 0.018). In PD patients, to suffer from constipation at V0 was associated with a decrease in the PD-CRS total score from V0 to V2 (β= –0.1; 95% CI, –4.36 – –0.27; p = 0.026) and having cognitive impairment at V2 (OR = 1.79; 95% CI, 1.01 – 3.17; p = 0.045). Conclusion: Constipation is associated with cognitive decline in PD patients but not in controls.

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Levodopa–carbidopa intrajejunal infusion in Parkinson’s disease: untangling the role of age

Journal of Neurology ◽

10.1007/s00415-020-10356-x ◽

2020 ◽

Author(s):

Francesca Morgante ◽

Valentina Oppo ◽

Margherita Fabbri ◽

Enrica Olivola ◽

Chiara Sorbera ◽

...

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Control Group ◽

Motor Symptoms ◽

Study Visit ◽

Non Motor Symptoms

Abstract Objectives Levodopa–Carbidopa Intrajejunal gel (LCIG) infusion is an effective intervention for people with advanced Parkinson’s disease (PD). Although age may not be a limiting factor for LCIG implant, no data are available on late elderly PD (LE-PD) subjects. In this cross-sectional, we aimed to demonstrate if older age may impact on quality of life (QoL), motor and non-motor symptoms severity, and profile of side effects in PD treated with LCIG. Methods Out of 512 PD subjects treated with LCIG at 9 Italian PD centers, we selected 25 LE-PD defined as age ≥ 80 years at last follow-up who were available to attend the study visit. Twenty-five PD patients (Control-PD, defined as age < 75 years at last follow-up) matched to LE-PD by disease and LCIG duration served as control group. The following motor and non-motor variables were ascertained: quality of life (PDQ-8), time spent in ON, wearing-off Questionnaire, Unified PD Rating Scale, freezing of gait questionnaire, Parkinson’s disease sleep scale-2, Non Motor Symptoms Scale (NMSS), and MOCA. Results No statistically significant differences were found between LE-PD and Control-PD on PDQ-8 and several motor and non-motor variables. LE-PD had less frequent and milder impulsive–compulsive behaviors and milder dyskinesia. At multivariable regression, worse quality of life was associated with UPDRS-III and NMSS scores but not to age at study visit and age at LICG implant. Rate of adverse effects was similar in both groups. Drop-out rate calculated in the whole PD cohort was comparable between the two groups. Conclusion Our data provide evidence that valuable LCIG infusion might be achieved in late elderly PD.

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The severity progression of non-motor symptoms in Parkinson’s disease: a 6-year longitudinal study in Taiwanese patients

Scientific Reports ◽

10.1038/s41598-021-94255-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yi-Chieh Chen ◽

Rou-Shayn Chen ◽

Yi-Hsin Weng ◽

Ying-Zu Huang ◽

Chiung Chu Chen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Longitudinal Study ◽

Disease Duration ◽

Rating Scale ◽

Medical Center ◽

Motor Symptoms ◽

Disease Rating ◽

Non Motor Symptoms

AbstractNonmotor symptoms (NMSs) cause major burden in patients with Parkinson’s disease (PD). Previous NMSs progression studies mostly focused on the prevalence. We conducted a longitudinal study to identify the progression pattern by the severity. PD patients recruited from the outpatient clinics of a tertiary medical center were evaluated by the Unified Parkinson's Disease Rating Scale and Non-Motor Symptoms Scale (NMSS). A retrospective study with three-step analysis was performed. Step 1, the NMSs severity was compared among patients stratified by disease duration every 2 years up to 10 years. Step 2, patients with repeated tests in 2 years were categorized into 4 groups by the diseased duration of every 5 years. Step 3, the NMSS score changes in 6 years follow-up were determined, and the dosage of anti-PD drugs was compared to the NMSs severity changes. 676 patients completed the step 1 analysis, which showed a trend of NMSs worsening but not significant until the disease duration longer than 4–6 years. Furthermore, the severity did not change between repeated evaluations in 2 years in all patients. The progression became apparent after 6 years. Individual symptoms had different progression patterns and the increment of medications was independent to NMSs evolution. We demonstrated the NMSs severity progression in Taiwanese PD patients and the independence of the medications and NMSs progression.

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Change in fear of falling in Parkinson's disease: a two-year prospective cohort study

International Psychogeriatrics ◽

10.1017/s1041610217002514 ◽

2017 ◽

Vol 31 (1) ◽

pp. 13-20 ◽

Cited By ~ 3

Author(s):

Tatjana Gazibara ◽

Darija Kisic Tepavcevic ◽

Marina Svetel ◽

Aleksandra Tomic ◽

Iva Stankovic ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Fall Prevention ◽

Rating Scale ◽

Fear Of Falling ◽

Daily Activities ◽

First Year ◽

Factors Associated ◽

Disease Rating

ABSTRACTBackground:Fear of falling in Parkinson's disease (PD) has been suggested as predictor of future falling. The purpose of this study was to compare fear of falling score after two years of follow-up with those observed at baseline and to assess factors associated with change in fear of falling over time.Methods:A total of 120 consecutive persons with PD were recruited and followed for two years. Fear of falling was assessed by using the 10-item Falls Efficacy Scale (FES). Occurrence of falling was registered during the first year of follow-up.Results:After two years, the average FES score statistically significantly changed (p = 0.003) from 30.5 to 37.5 out of 100 (increase of 22.9%). We observed that median scores of all FES items, except for “Preparing a meal, not requiring carrying of heavy or hot objects” and “Personal grooming,” significantly increased after two-year follow-up. After accounting for age, gender, PD duration, levodopa dosage, Hoehn and Yayhr stage, Unified Parkinson's Disease Rating Scale score three, depression, anxiety, and falling, we observed that sustaining greater number of falls in the first year of follow-up was associated with higher increase in FES score after two years (odds ratio 3.08, 95% confidence interval 1.30–4.87).Conclusion:After two years of follow-up, we observed a decrease in confidence at performing nearly all basic daily activities. Fall prevention programs should be prioritized in management of PD.

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Evolution of Apathy in Early Parkinson's Disease: A 4-Years Prospective Cohort Study

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2020.620762 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ruwei Ou ◽

Junyu Lin ◽

Kuncheng Liu ◽

Zheng Jiang ◽

Qianqian Wei ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Proportional Hazards ◽

Rating Scale ◽

Early Stage ◽

Cox Proportional Hazards ◽

Lars Score ◽

Disease Rating ◽

Non Motor Symptoms

Objective: We investigated the prevalence, evolution, associated factors, and risk factors of apathy in a cohort of patients with early-stage Parkinson's disease (PD), who underwent a 4-years prospective follow-up.Methods: This study included 188 patients with PD (baseline disease duration <3 years) who underwent an annual evaluation using the Lille Apathy Rating Scale (LARS). Based on the cut-off value of −21 observed on the LARS, patients were categorized as PD with and without apathy. The generalized estimating equations (GEE) model was utilized to determine the factors associated with apathy, and the Cox proportional-hazards regression model was used to determine the predictors of apathy.Results: Apathy increased from a baseline rate of 18.6–28.8% after 4 years; notably, this rate was not persistent across patients' visits. The LARS score was independently associated with the male sex (B 8.131, p = 0.009), low Frontal Assessment Battery (FAB) scores (B 0.567, p = 0.011), low attention scores on the Montreal Cognitive Assessment (MOCA) test (B 0.217, p = 0.026), high Hamilton Depression Rating Scale (HDRS) scores (B 1.362, p < 0.001), high Unified Parkinson's Disease Rating Scale (UPDRS) part III scores (B 1.147, p < 0.001), and prolonged follow-up time (B 1.785, p = 0.048). A high HDRS score was the only predictor of apathy in PD [hazard ratio (HR) 1.043, p = 0.026].Conclusions: The risk of apathy is higher in men with progressive PD accompanied by disease-specific motor and non-motor symptoms. Depression during early-stage PD is a primary risk factor for apathy in PD.

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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

Journal of Parkinson s Disease ◽

10.3233/jpd-212860 ◽

2021 ◽

pp. 1-16

Author(s):

Michael Bartl ◽

Mohammed Dakna ◽

Sebastian Schade ◽

Tamara Wicke ◽

Elisabeth Lang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Clinical Trials ◽

Rating Scale ◽

De Novo ◽

Longitudinal Change ◽

Single Center ◽

Square Roots ◽

Disease Rating

Background: 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. Objective: To systematically dissect MDS-UPDRS to predict PD progression. Methods: 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. Results: 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. Conclusion: 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.

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BILATERAL SUBTHALAMIC DEEP BRAIN STIMULATION IN A PATIENT WITH PARKINSON'S DISEASE WHO HAD PREVIOUSLY UNDERGONE THALAMOTOMY AND AUTOLOGOUS ADRENAL GRAFTING IN THE CAUDATE NUCLEUS

Neurosurgery ◽

10.1227/01.neu.0000245585.93284.15 ◽

2006 ◽

Vol 59 (5) ◽

pp. E1140-E1140 ◽

Cited By ~ 5

Author(s):

Francesco Vergani ◽

Andrea Landi ◽

Angelo Antonini ◽

Erik P. Sganzerla

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Rating Scale ◽

Disease Rating ◽

Noticeable Reduction ◽

Surgical Treatments ◽

Deep Brain

Abstract OBJECTIVE Subthalamic (Stn) deep brain stimulation (DBS) is a valid surgical therapy for the treatment of severe Parkinson's disease. In recent years, StnDBS has been proposed for patients who previously received other surgical treatments, such as thalamotomy and pallidotomy. Nonetheless, there is no consensus about the indications of DBS in patients who previously underwent surgery. To the best of our knowledge this is the first reported case of a patient treated with DBS after previous thalamotomy and adrenal grafting. CLINICAL PRESENTATION A 62-year-old man with a long history (more than 30 yr) of Parkinson's disease received unilateral thalamotomy and autologous adrenal graft on two independent occasions. Thalamotomy led to a significant improvement, although limited to the control of contralateral tremor. The autologous adrenal graft was of no benefit. For the subsequent occurrence of L-dopa related dyskinesias and severe “off” periods, the patient was referred to our center for StnDBS. INTERVENTION The patient underwent bilateral StnDBS, obtaining a satisfactory improvement of rigidity and bradykinesia on both sides. The 1-year follow-up evaluation showed a 46% improvement in the Unified Parkinson's Disease Rating Scale motor section, along with a noticeable reduction in antiparkinsonian therapy (81%). CONCLUSION This case is consistent with previous reports from the literature, suggesting that StnDBS is feasible and safe, even in patients who previously received other surgical treatments for Parkinson's disease, such as thalamotomy or cell grafting.

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Predictors of Loss of Functional Independence in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up and Comparison with a Control Group

Diagnostics ◽

10.3390/diagnostics11101801 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1801

Author(s):

Diego Santos García ◽

Teresa de Deus Fonticoba ◽

Carlos Cores Bartolomé ◽

Lucía Naya Ríos ◽

Lucía García Roca ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Activities Of Daily Living ◽

Daily Living ◽

Functional Independence ◽

Control Group ◽

Lemeshow Test ◽

Group A ◽

And Control

Background and objective: 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). Patients and Methods: 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%. Results: 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; p < 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; p = 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; p = 0.009), have longer disease duration (OR = 1.152; p = 0.002), have a non-tremoric motor phenotype at baseline (OR = 3.574; p = 0.004), have a higher score at baseline in FOGQ (OR = 1.244; p < 0.0001) and BDI-II (OR = 1.080; p = 0.008), have a lower score at baseline in PD-CRS (OR = 0.963; p = 0.008), and have a greater increase in the score from V0 to V2 in UPDRS-IV (OR = 1.168; p = 0.0.29), FOGQ (OR = 1.348; p < 0.0001) and VAFS-Mental (OR = 1.177; p = 0.013) (adjusted R-squared 0.52; Hosmer and Lemeshow test = 0.94) were all found to be independent predictors of FD at V2. Conclusions: 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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Impact of SAfinamide on Depressive Symptoms in Parkinson’s Disease Patients (SADness-PD Study): A Multicenter Retrospective Study

Brain Sciences ◽

10.3390/brainsci11020232 ◽

2021 ◽

Vol 11 (2) ◽

pp. 232

Author(s):

Esteban Peña ◽

Carmen Borrué ◽

Marina Mata ◽

Juan Carlos Martínez-Castrillo ◽

Araceli Alonso-Canovas ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Serotonin Syndrome ◽

Rating Scale ◽

Motor Symptoms ◽

Motor Complications ◽

Daily Life Activities ◽

Patient Global Impression ◽

Disease Rating

Background: We aimed to assess the effects of safinamide on depression, motor symptoms, and the serotonin syndrome related to its co-administration with antidepressants in patients with Parkinson’s disease (PD). Methods: We retrospectively analyzed the data of patients at 1 and 3 months of follow-up compared to baseline. Results: n = 82 (safinamide 50 mg = 22, 100 mg = 60, with antidepressants = 44). First, we found improvement in depression (Hamilton Depression Rating Scale: −6 ± 5.10 at 1 month and −7.27 ± 5.10 at 3 months, p < 0.0001; Patient Global Impression of Improvement Scale: 60.3% and 69.5% of patients at 1 and 3 months reported some improvement). Second, safinamide improved the daily life activities and motor symptoms/motor complications (Unified Parkinson’s Disease Rating Scale (UPDRS-II): −2.51 ± 6.30 and −2.47 ± 6.11 at 1 and 3 months, p < 0.0001; III: −3.58 ± 8.68 and −4.03 ± 8.95 at 1 and 3 months, p < 0.0001; IV: −0.61 ± 2.61 and −0.8 ± 2.53 at 1 and 3 months, p < 0.0001). Third, 7.31% and 8.53% of patients developed non-severe adverse events related to safinamide at 1 and 3 months. Serotonin syndrome was not observed in the patients treated with antidepressants; some isolated serotonin syndrome symptoms were reported. Conclusions: Safinamide could be useful for treating depression in PD; it was effective for motor symptoms and motor complications and safe even when co-administered with antidepressants.

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Intestinal Decontamination Therapy for Dyskinesia and Motor Fluctuations in Parkinson's Disease

Frontiers in Neurology ◽

10.3389/fneur.2021.729961 ◽

2021 ◽

Vol 12 ◽

Author(s):

José Fidel Baizabal-Carvallo ◽

Marlene Alonso-Juarez ◽

Robert Fekete

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Neurodegenerative Disorder ◽

Pharmacological Therapy ◽

Motor Fluctuations ◽

Disease Rating ◽

Intestinal Decontamination ◽

Statistical Improvement

Parkinson's disease is neurodegenerative disorder with an initial robust response to levodopa. As the disease progresses, patients frequently develop dyskinesia and motor fluctuations, which are sometimes resistant to pharmacological therapy. In recent years, abnormalities in gut microbiota have been identified in these patients with a possible role in motor manifestations. Dysbiosis may reduce levodopa absorption leading to delayed “On” or “no-On” states. Among 84 consecutive patients with PD, we selected 14 with levodopa-induced dyskinesia and motor fluctuations with a Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part IV ≥ 8 points following a trial of pharmacological adjustment 2–3 months prior to study enrollment or adjustments in deep brain stimulation therapy. Patients received treatment with sodium phosphate enema followed by oral rifaximin and polyethylene glycol for 7 and 10 days, respectively. Evaluations between 14 to 21 days after starting treatment showed improvement in MDS-UPDRS-IV (P = 0.001), including duration (P = 0.001) and severity of dyskinesia (P = 0.003); duration of medication “Off”-state (P = 0.004); functional impact of motor fluctuations (P = 0.047) and complexity of motor fluctuations (P = 0.031); no statistical improvement was observed in “Off” dystonia (P = 0.109) and total motor scores (P = 0.430). Marked to moderate improvement in dyskinesia was observed in 57% of cases with blinded evaluation of videos. About 80% of patients perceived moderate to robust improvement at follow-up. A therapeutic strategy aimed at decontamination of intestines showed benefit in motor fluctuations and dyskinesia. Further studies should confirm and clarify the mechanism of improvement observed in these patients.

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