England Activities Of Daily Living Research Articles

The effects of treatment with pimavanserin on activities of daily living in patients with Parkinson's disease psychosis: a 16-week, single-arm, open-label study.

More than half of patients with Parkinson's disease will experience psychosis symptoms in the form of hallucinations or delusions at some point over the course of their disease. These symptoms can significantly impact patients' health-related quality of life, cognitive abilities, and activities of daily living (ADLs) and function. Clinical assessment of how psychosis impacts these measures is crucial; however, few studies have assessed this sufficiently, in part due to a lack of appropriate scales for comprehensively assessing function. The objective was to assess how symptoms of Parkinson's disease psychosis (PDP) impact ADLs and function, cognitive function, and health-related quality of life. To address this unmet need, we utilized a modified version of the Functional Status Questionnaire (mFSQ) to measure the impact of psychosis on ADLs and function in patients with PDP treated with pimavanserin, a US Food and Drug Administration-approved medication to treat hallucinations and delusions associated with PDP. Eligible patients entered a 16-week, single-arm, open-label study of oral pimavanserin (34 mg) taken once daily. The primary endpoint was change from baseline to Week 16 on the mFSQ. Secondary endpoints included the Movement Disorders Society-modified Unified Parkinson's Disease Rating Scale (MDS-UPDRS) I and II; Schwab and England ADL; Clinical Global Impression-Severity of Illness (CGI-S), Clinical Global Impression-Improvement (CGI-I), and Patient Global Impression-Improvement (PGI-I), and were also measured as change from baseline to Week 16 using mixed-effects model for repeated measures (MMRM) and least-squares mean (LSM). Our results in a proof-of-concept, 16-week, open-label clinical study in 29 patients demonstrated that an improvement in psychosis symptoms following treatment with pimavanserin was associated with improvements in multiple measures of ADLs and function. Notably, a significant improvement was found on the primary endpoint, change from baseline to Week 16 in mFSQ score [LSM [SE] 14.0 [2.50], n = 17; 95% CI (8.8, 19.3); p < 0.0001]. These findings highlight the potential for improvement in function with improvement of psychosis symptoms in patients with PDP and suggest that the mFSQ may be a measurement tool to evaluate the level of improvement in function. ClinicalTrials.gov Identifier: NCT04292223.

Unexpected gender differences in progressive supranuclear palsy reveal efficacy for davunetide in women

Progressive supranuclear palsy (PSP) is a pure tauopathy, implicating davunetide, enhancing Tau-microtubule interaction, as an ideal drug candidate. However, pooling patient data irrespective of sex concluded no efficacy. Here, analyzing sex-dependency in a 52 week-long- PSP clinical trial (involving over 200 patients) demonstrated clear baseline differences in brain ventricular volumes, a secondary endpoint. Dramatic baseline ventricular volume-dependent/volume increase correlations were observed in 52-week-placebo-treated females (r = 0.74, P = 2.36–9), whereas davunetide-treated females (like males) revealed no such effects. Assessment of primary endpoints, by the PSP Rating Scale (PSPRS) and markedly more so by the Schwab and England Activities of Daily Living (SEADL) scale, showed significantly faster deterioration in females, starting at trial week 13 (P = 0.01, and correlating with most other endpoints by week 52). Twice daily davunetide treatments slowed female disease progression and revealed significant protection according to the SEADL scale as early as at 39 weeks (P = 0.008), as well as protection of the bulbar and limb motor domains considered by the PSPRS, including speaking and swallowing difficulties caused by brain damage, and deterioration of fine motor skills, respectably (P = 0.01), at 52 weeks. Furthermore, at 52 weeks of trial, the exploratory Geriatric Depression Scale (GDS) significantly correlated with the SEADL scale deterioration in the female placebo group and demonstrated davunetide-mediated protection of females. Female-specific davunetide-mediated protection of ventricular volume corresponded to clinical efficacy. Together with the significantly slower disease progression seen in men, the results reveal sex-based drug efficacy differences, demonstrating the neuroprotective and disease-modifying impact of davunetide treatment for female PSP patients.

Phenotype and natural history of mitochondrial membrane protein-associated neurodegeneration.

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is an ultraorphan neurogenetic disease from the group of neurodegeneration with brain iron accumulation (NBIA) disorders. Here we report cross-sectional and longitudinal data to define the phenotype, to assess disease progression and to estimate sample sizes for clinical trials. We enrolled patients with genetically confirmed MPAN from the Treat Iron-Related Childhood-Onset Neurodegeneration (TIRCON) registry and cohort study, and from additional sites. Linear mixed-effect modelling (LMEM) was used to calculate annual progression rates for the Unified Parkinson's Disease Rating Scale (UPDRS), Barry-Albright Dystonia (BAD) scale, Schwab and England Activities of Daily Living (SE-ADL) scale and the Pediatric Quality of Life Inventory (PedsQL). We investigated 85 MPAN patients cross-sectionally, with functional outcome data collected in 45. Median age at onset was 9 years and the median diagnostic delay was 5 years. The most common findings were gait disturbance (99%), pyramidal involvement (95%), dysarthria (90%), vision disturbances (82%), with all but dysarthria presenting early in the disease course. After 16 years with the disease, 50% of patients were wheelchair dependent. LMEM showed an annual progression rate of 4.5 points in total UPDRS. The total BAD scale score showed no significant progression over time. The SE-ADL scale and the patient- and parent-reported PedsQL showed a decline of 3.9%, 2.14 and 2.05 points, respectively. No patient subpopulations were identified based on longitudinal trajectories. Our cross-sectional results define the order of onset and frequency of symptoms in MPAN, which will inform the diagnostic process, help to shorten diagnostic delay and aid in counselling patients, parents and caregivers. Our longitudinal findings define the natural history of MPAN, reveal the most responsive outcomes and highlight the need for an MPAN-specific rating approach. Our sample size estimations inform the design of upcoming clinical trials.

Compliance with National and International Guidelines in the Treatment of Nonmotor Symptoms in Late-Stage Parkinson's Disease.

National as well as international Parkinson's disease (PD) treatment guidelines are available to guide clinicians. Previous research has shown that nonmotor symptoms (NMS) are pronounced in late-stage PD and has suggested that current treatment is insufficient and could be improved. The aim of this study was to investigate to which degree the national and international treatment guidelines are followed in the treatment of NMS in late-stage PD. This Swedish cohort was part of the Care of Late-Stage Parkinsonism (CLaSP) study. Late-stage PD was defined as Hoehn and Yahr stages IV-V in "on" and/or ≤50% on the Schwab and England Activities of Daily Living (ADL) scale. NMS were assessed with the NMS scale (NMSS), cognition with the Mini-Mental State Examination (MMSE), and depressive symptoms with the Geriatric Depression Scale (GDS-30). Symptomatic individuals were defined as ≥ 6 on an item of the NMSS; for dementia, a cutoff of ≤18 on the MMSE; for depression, a cutoff of ≥10 on the GDS. All 107 participants exhibited NMS to various degrees and severities; the median NMSS score was 91. Among symptomatic individuals, for depressive symptoms, 37/63 (59%) were treated with antidepressants; for hallucinations and delusions, 9/18 (50%) and 5/13 (38%) were treated with antipsychotics; and for dementia, 9/27 (33%) were treated with rivastigmine and 1 (4%) was treated with donepezil. For orthostatic hypotension, 11/19 (58%) with lightheadedness and 7/8 (88%) with fainting were treated with antihypotensives; for sialorrhea, 2/42 (5%) were treated with botulinum toxin; and for constipation, 19/35 (54%) were treated with laxatives. For insomnia, 4/16 (25%) were treated with hypnotics, and for daytime sleepiness, 1/29 (3%) was treated with psychostimulants. The present analyses suggest a need for clinicians to further screen for and treat NMS. Optimizing treatment of NMS according to the national and international treatment guidelines may improve symptomatology and enhance quality of life in late-stage PD.

A 16-Week Open-Label Study of the Effects of Treatment With Pimavanserin on Activities of Daily Living in Subjects With Parkinson’s Disease Psychosis

AbstractIntroductionAccurate assessment of disability associated with Parkinson’s Disease Psychosis (PDP) is essential and has been poorly studied. Patients often have poor insight on impact of PDP on daily function. This phase 4 study is the first to evaluate the impact of pimavanserin on activities of daily living (ADL) in PDP patients.MethodsEligible PDP patients entered a 16-week single-arm, open-label study of oral pimavanserin (34 mg) taken once daily. Primary endpoint (modified Functional Status Questionnaire [mFSQ]) and secondary endpoints (MDS-UPDRS I &amp; II; Schwab and England ADL; CGI-S, CGI-I, and PGI-I) were measured as change from baseline to Week 16 using mixed-effects model for repeated measures (MMRM) and least-squares means (LSM).Results29 patients were treated with pimavanserin, of which 24 (82.8%) completed the study. Treated patients demonstrated significant improvements in LSM (SE) mFSQ score change from baseline to Week 12 (11.5 [2.44]) and Week 16 (14.0 [2.50]; both p&lt;0.0001). Significant improvements (p&lt;0.05) were also observed for all secondary outcomes at Week 16 (MDS-UPDRS Part I: -6.3 [0.97]; MDS-UPDRS Part II: -2.6 [0.98]; CGI-S: -1.5 [0.25]; CGI-I: 1.9 [0.17]; PGI-I: 2.0 [0.22], except for Schwab and England ADL. No new safety signals were observed.ConclusionFunctional outcomes and psychosis measures improved in PDP patients treated with pimavanserin, with safety findings consistent with previous studies. Our findings highlight the positive effect of pimavanserin in improving ADLs in patients with PDP.FundingAcadia Pharmaceuticals Inc.

Long-Term Effects of Subthalamic Stimulation on Motor Symptoms and Quality of Life in Patients with Parkinson’s Disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting both motor functions and quality of life (QoL). This study compared motor symptoms and QoL in patients with PD before and at 1 and 5 years after subthalamic nucleus deep brain stimulation (STN-DBS) surgery in Taiwan. This study included 53 patients with PD undergoing STN-DBS. The motor symptoms improved by 39.71 ± 26.52% and 18.83 ± 37.15% in the Unified Parkinson's Disease Rating Scale (UPDRS) part II and by 36.83 ± 22.51% and 22.75 ± 36.32% in the UPDRS part III at 1 and 5 years after STN-DBS in the off-medication/on-stimulation state, respectively. The Hoehn and Yahr stage significantly improved at the 1-year follow-up but declined progressively and returned to the baseline stage 5 years post-surgery. The Schwab and England Activities of Daily Living improved and sustained for 5 years following STN-DBS. Levodopa equivalent daily dose decreased by 35.32 ± 35.87% and 15.26 ± 65.76% at 1 and 5 years post-surgery, respectively. The QoL revealed significant improvement at 1 year post-surgery; however, patients regressed to near baseline levels 5 years post-surgery. The long-term effects of STN-DBS on motor symptoms were maintained over 5 years after STN-DBS surgery. At the same time, STN-DBS had no long-lasting effect on QoL. The study findings will enable clinicians to become more aware of visible and invisible manifestations of PD.

Brain and Systemic Inflammation in De Novo Parkinson's Disease.

To assess the presence of brain and systemic inflammation in subjects newly diagnosed with Parkinson's disease (PD). Evidence for a pathophysiologic role of inflammation in PD is growing. However, several key gaps remain as to the role of inflammation in PD, including the extent of immune activation at early stages, potential effects of PD treatments on inflammation and whether pro-inflammatory signals are associated with clinical features and/or predict more rapid progression. We enrolled subjects with de novo PD (n = 58) and age-matched controls (n = 62). Subjects underwent clinical assessments, including the Movement Disorder Society-United Parkinson's Disease rating scale (MDS-UPDRS). Comprehensive cognitive assessment meeting MDS Level II criteria for mild cognitive impairment testing was performed. Blood was obtained for flow cytometry and cytokine/chemokine analyses. Subjects underwent imaging with 18 F-DPA-714, a translocator protein 18kd ligand, and lumbar puncture if eligible and consented. Baseline demographics and medical history were comparable between groups. PD subjects showed significant differences in University of Pennsylvania Smell Identification Test, Schwab and England Activities of Daily Living, Scales for Outcomes in PD autonomic dysfunction, and MDS-UPDRS scores. Cognitive testing demonstrated significant differences in cognitive composite, executive function, and visuospatial domain scores at baseline. Positron emission tomography imaging showed increased 18 F-DPA-714 signal in PD subjects. 18 F-DPA-714 signal correlated with several cognitive measures and some chemokines. 18 F-DPA-714 imaging demonstrated increased central inflammation in de novo PD subjects compared to controls. Longitudinal follow-up will be important to determine whether the presence of inflammation predicts cognitive decline. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Nomogram to Predict the Probability of Functional Dependence in Early Parkinson's Disease.

Early identification of Parkinson's disease (PD) patients at risk for becoming functionally dependent is important for patient counseling. Several models describing the relationship between predictors and outcome have been reported, however, most of these require computer software for practical use. Here we report the development of a risk nomogram allowing an approximate graphical computation of the risk of becoming functionally dependent in early PD. We analyzed data form the Parkinson's Progression Markers Initiative cohort of newly diagnosed PD patients from baseline through the first 5 years of follow-up. Functional dependence was defined as a score < 80 on the Schwab & England Activities of Daily Living scale. A binary logistic model was developed to estimate the risk of functional dependence and based on the results, a nomogram for the prediction of functional dependence was drawn in order to provide an easy-to-use tool in clinical and academic settings as a part of personalized medicine approach to PD treatment. At baseline, three patients and over the five-year follow-up, 85 (22%) out of 395 patients were functionally dependent as scored by the Schwab & England Activities of Daily Living rating scale. The binary logistic model showed that clinical parameters such as MDS-UPDRS I (rater part), MDS-UPDRS II, and MDS-UPDRS axial motor score were significant predictors for functional dependence within 5 years. We here provide an easy-to-use tool to estimate the risk of functional dependence in PD patients based on the MDS-UPDRS part I, II and axial motor score.

Subjective Assessments of Voice in Parkinson's Disease Subjects with and without STN-DBS Therapy.

The causal relation between STN-DBS and speech problems and the associated clinical features are in the incipient stages of being investigated. All the Parkinson's disease (PD) subjects with and without STN-DBS who applied to our movement disorders outpatient clinics between January 2022 and June 2022 and agreed to participate in the study were enrolled. The demographic data and clinical features were noted. Besides, the MDS-UPDRS was administered during the medication off-state in all subjects. All the participants completed the voice handicap index (VHI). Besides, the Freezing of Gait Questionnaire (FOGQ) and the quality of life (QoL) scales including the Parkinson's Disease Questionnaire (PDQ-39) and the Schwab and England Activities of Daily Living (ADL) scale were also administered to all the individuals. We have included 66 patients with PD (F/M = 23/43). Thirty-five patients were those with DBS therapy whereas 31 patients were without. The results of the comparative analyses between the patients with and without DBS therapy revealed that the DBS group had a higher disease duration (P = 0.006) and FOGQ scores (P = 0.008). The VHI scores did not differ between groups (P = 0.577), and the correlation analyses did not reveal an association between the VHI scores and the duration of DBS therapy. However, the VHI scores correlated with the disease duration as well as the FOG scores. We did not find convincing evidence supporting the increased risk of speech disturbance with STN-DBS therapy. We suggest that the frequent existence of speech disturbance in this patient subgroup with STN-DBS is associated with the classical nature of PD.

Activities of daily living as a longitudinal moderator of the effect of autonomic dysfunction on anxiety and depression of Parkinson's patients.

BackgroundThere is no clear time point for the onset of depression and anxiety in Parkinson's disease (PD), and their atypical physical symptoms often overlap with other nonmotor symptoms. Autonomic dysfunction usually appears earlier than motor symptoms, seriously impairing activities of daily living (ADL), even quality of life. Whether autonomic dysfunction can affect depression and anxiety in PD patients through ADL is still unclear.MethodsWe conducted three progressive autoregressive mediation models to evaluate whether ADL may mediate the association between autonomic symptom burden, where the mediation chain with autonomic function as an independent variable, ADL as a mediating variable, and anxiety and depression as dependent variables. The ADL of PD patients were measured by the Scales for Outcomes in Parkinson's disease‐Autonomic (SCOPA‐AUT) and Modified Schwab and England ADL scale, respectively, and the status of depression and anxiety were measured by the Geriatric Depression Scale (GDS) and State‐Trait Anxiety Inventory (STAI).ResultsThere were 338 PD patients, including 220 males and 118 females. Demographic information, including age, gender, and education level, were not correlated with the depression and anxiety. Model III had the smallest AIC (AIC = 12,669.89), and the cross‐lagged relations were not statistically significant, so we selected Model II as the optimal model. In Model II, longitudinal autoregressive mediated effect and longitudinal mediated effect of autonomic dysfunction affecting anxiety and depression through ADL were not statistically significant, suggesting longitudinal changes of autonomic dysfunction were independent of anxiety and depression through ADL. Contemporaneous mediated effects of autonomic dysfunction affecting anxiety and depression through ADL were statistically significant, suggesting contemporaneous autonomic dysfunction may contribute to anxiety and depression through ADL.ConclusionsTargeted prevention and intervention measures for autonomic dysfunction and ADL should be taken to preserve and improve self‐perceived life satisfaction in the clinical practice and preventive health care of PD.

Staging Parkinson's Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life.

Introduction In a degenerative disorder such as Parkinson's disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr's motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient's quality of life (QoL) with regard to a defined clinical stage. Materials and Methods Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0–20; B: NMSS = 21–40; C: NMSS = 41–70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. Results A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p < 0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (p < 0.005; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p < 0.0001). Conclusion The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden.

Associations Between Amantadine Usage, Gait, and Cognition in PSP: A post-hoc Analysis of the Davunetide Trial.

Introduction: Amantadine anecdotally improves gait in progressive supranuclear palsy (PSP) but definitive data is lacking. We investigated associations between amantadine usage, gait, cognition, and activities of daily living in 310 subjects with PSP using data from the davunetide trial.Method: We compared baseline demographics, PSP Rating Scale (PSPRS), Repeat Battery for the Assessment of Neuropsychological Status (RBANS), and Schwab and England Activities of Daily Living (SEADL) scores between subjects taking vs. not taking amantadine using chi-square tests for categorical variables and independent sample t-tests for continuous variables. Using the general linear model (GLM), we tested whether group status predicted total PSPRS, PSPRS-gait and midline, total RBANS, RBANS-attention, and SEADL before and after the 52-weeks follow-up.Results: Subjects taking vs. not taking amantadine were similar at baseline, except subjects taking amantadine had a higher Clinical Global Impression (CGI) Score (p = 0.01). However, the CGI change score did not differ between groups at week 52 (p = 0.10). Using GLM models (controlling for covariates), we found that subjects taking vs. not taking amantadine did not significantly predict total PSPRS, PSPRS-gait and midline, total RBANS, RBANS-attention, or SEADL at baseline, week 52, or the change score between baseline and week 52.Discussion: This post-hoc analysis of the davunetide trial did not find an association between amantadine and gait or cognitive measures in PSP, but was not powered to find such a difference. Future studies should still examine amantadine for symptomatic benefit in multiple PSP subtypes.

Creation of a gene expression classifier for predicting Parkinson's disease rate of progression.

Parkinson's disease (PD) etiology is heterogeneous, genetic, and multi-factorial, resulting in a varied disease from a mild slow progression to a more severe rapid progression. Prognostic information on the nature of the patient's disease at diagnosis aids the physician in counseling patients on treatment options and life planning. In a cohort of PD patients from the PPMI study, the relative gene expression levels of SKP1A, UBE2K, ALDH1A1, PSMC4, HSPA8 and LAMB2 were measured in baseline blood samples by real-time quantitative PCR. At baseline PD patients were up to 2years from diagnosis, H&Y scale ≤ 2 and PD treatment naïve. PD-Prediction algorithm comprised of ALDH1A1, LAMB2, UBE2K, SKP1A and age was created by logistic regression for predicting progression to ≤ 70% Modified Schwab and England Activities of Daily Living (S&E-ADL). In relation to patients negative for PD-Prediction (n = 180), patients positive (n = 30) for Cutoff-1 (at 82% specificity, 80.0% sensitivity) had positive hazard ratio (HR+) of 10.6 (95% CI, 2.2-50.1), and positive (n = 23) for Cutoff-2 (at 93% specificity, 47% sensitivity) had HR+ of 17.1 (95% CI, 3.2-89.9) to progress to ≤ 70% S&E-ADL within 3years (P value < 0.0001). Likewise, patients positive for PD-Prediction Cutoff-1 (n = 49) had HR+ 4.3 (95% CI, 1.6-11.6) for faster time to H&Y 3 in relation to patients negative (n = 170) for PD-Prediction (P value = 0.0002). Our findings show an algorithm that seems to predict fast PD progression and may potentially be used as a tool to assist the physician in choosing an optimal treatment plan, improving the patient's quality of life and overall health outcome.

Prevalence, clinical features and factors associated with psychosis among Idiopathic Parkinson’s Disease (IPD) patients in Universiti Kebangsaan Malaysia Medical Centre (UKMMC)

Introduction: This was a cross sectional study of the prevalence of psychosis and its characteristic in patients with Idiopathic PD (IPD) attending the neurology clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM). Methods: The assessment was using a structured demographic data and clinical information questionnaire, Mini-International Neuropsychiatric Interview (MINI) 6.0.0, Starkstein’s Apathy Scale (AS), Mini Mental State Examination (MMSE), Movement Disorder Society – Unified Parkinson Disease Rating Scale (MDS-UPDRS) Q1-Q6, Hoehn and Yahr (H&amp;Y) stages of PD and Schwab and England Activities of Daily Living (ADL) scale. Results: 112 patients were studied. Psychosis was identified in 39 (34.8 %) patients (33 patients with hallucination only, 6 with hallucination and delusion (psychotic disorder) and none with delusions only). Among patients experiencing hallucinations, 14 (35.9%) had a visual hallucination only, 12 (30.8%) had auditory hallucinations only, and 13 (33.3%) had both visual and auditory hallucinations. Psychosis were more common in IPD patients with cognitive impairment using MDSQ1 scoring (OR 0.15; 95% CI, 0.05-0.63; P = p‹0.05) while others variables were not significant. The analysis, among patients with psychotic symptoms only and patients with psychotic disorder showed education level (p&lt;0.05), duration of illness (OR 1.8; 95% CI, (-10.7 - -3.5; p &lt;0.01), cognitive impairment score - MDSQ1 (OR 0.2; 95% CI, 0.2-0.9; p&lt;0.01), H&amp;Y score (OR 0.4; 95% CI, -2.1- -0.6; p&lt;0.01) and ADL score (OR 0.6; 95% CI, 0.3 – 2.6; p&lt;0.05) were significant. Conclusions: Lower education level, longer duration of illness, more advance stage of Parkinson disease and less functioning in ADL were significant in psychotic disorder in IPD.

Cost of Parkinson’s disease among Filipino patients seen at a public tertiary hospital in Metro Manila

BackgroundCost of illness (COI) studies are used to estimate the economic burden of a particular disease. The chronicity of Parkinson's disease (PD) and its lack of treatment make its projected economic burden to grow substantially over the next few decades. MethodsTo evaluate the cost of having PD, a COI study was done in a public tertiary hospital in Metro Manila, Philippines. PD patients who were consecutively seen at out patient clinic for a period of six months were included in this study and were interviewed using a ready-made financial burden questionnaire. To identify the possible factors that may affect the cost, European Quality of Life 5 Dimensions (EQ5D), Montreal Cognitive Assessment-Philippines (MoCA-P), Hospital Anxiety and Depression Scale-Pilipino (HADS-P), Unified Parkinson's Disease Rating Scale (UPDRS) motor and activities of daily living (ADL) scores, Schwab and England ADL and Hoehn and Yahr scoring were also administered. ResultsThirty three consecutive PD patients (mean age: 58.4 yrs, men: 52%) were identified. The annual total cost of PD per capita was Php 308,796 (USD 6175) with direct cost accounting for 23% and indirect cost 77%. The main cost components for direct medical, direct non-medical and indirect cost were pharmacotherapy (97%), home care (42.6%) and productivity loss (100%) respectively. The factors observed to have high cost of PD included being male, married, employed, the presence of wearing off phenomenon, low MOCA-P and HADS-P, low Schwab and England ADL and increasing Hoehn and Yahr stage. ConclusionThis study showed that PD is a costly neurodegenerative disease that may pose a significant economic burden on patients, health care system and society.

Application of intracranial lead reconstruction in deep brain stimulation therapy in patients with Parkinson's disease

To evaluate the feasibility of applying intracranial lead reconstruction in deep brain stimulation (DBS) therapy for Parkinsonism. We retrospectively collected the clinical data from 27 patients with Parkinson's disease (PD), who received bilateral subthalamic nucleus (STN) DBS therapy between January, 2016 and December, 2017. According to the position of the selected optimal stimulating contact of the implanted leads, the patients were divided into group A with the stimulating contacts of the bilateral leads in the STN, group B with unilateral stimulating contacts in the STN, and group C with bilateral stimulating contacts outside the STN. All the patients were assessed for improvement using Hoehn-Yahr stage, the third part of United Parkinson's Disease Rating Scale (UPDRS Ⅲ), Schwab and England Activities of Daily Living (SE-ADL), and L-dopa equivalent daily dose (LEDD). The consistency between the optimal stimulating contact selected by lead reconstruction and that by standard postoperative programming procedure was also evaluated. The patients in all the 3 groups showed postoperative improvements in Hoehn-Yahr stage, UPDRS Ⅲ score, SE-ADL score, and LEDD in the medication-off state. But at 12 months of the follow-up, such improvements were maintained only in the patients of group A. The optimal stimulating contacts selected by lead reconstruction and standard postoperative programming procedure had a matching rate of up to 77.78% (42/54), and the coordinates of the optimal contacts selected by the two methods showed no significant difference. Intracranial lead reconstruction facilitates the study of the association between the implant site of the leads and the clinical outcome of DBS therapy for PD and allows the precise selection of the optimal contact of the implanted leads in postoperative programming of DBS.

Barthel Index and modified Rankin Scale: Psychometric properties during medication phases in idiopathic Parkinson disease.

Independence in activities of daily living (ADL) is one of the most important aspects in planning treatment for people with Parkinson disease (PD). The Barthel Index (BI) and modified Rankin Scale (mRS) are commonly used in neurological diseases. This study was conducted to confirm the validity and reliability of the BI and mRS in PD during ON and OFF medication phases. We included 260 individuals with a diagnosis of idiopathic PD. The disability in ADL was measured by the BI, mRS, Parkinson's Disease Questionnaire-39 (PDQ-39), Unified Parkinson Disease Rating Scale-Activities of Daily Living (UPDRS-ADL), and Schwab and England ADL scale (SE). Test-retest, inter-rater reliability, and internal consistency were assessed by the intra-class correlation (ICC) and Cronbach α coefficients. Dimensionality was evaluated by factor analysis. Convergent validity was assessed by the SE, Berg Balance Scale (BBS), PDQ-39 and UPDRS-ADL. For the 260 participants (187 [71.9%] males; mean [SD] age 60.3 [12.3] years), both the BI and mRS achieved an acceptable level of test-retest and inter-rater reliability (ICC=0.77 to 0.91) in ON and OFF medication phases. The Cronbach α for BI was 0.85 and 0.88, respectively. We found 1 and 2 factors for BI in ON and OFF phases, respectively. Investigation of convergent validity showed moderate to high correlation for the BI with the UPDRS-ADL, SE, PDQ-39 (ADL), BBS and mRS scores in ON and OFF phases (ρ=0.51-0.74) and mRS with SE, UPDRS-ADL, PDQ-39 (ADL) and BBS scores (ρ=0.48-0.82). The BI and mRS showed acceptable validity and reliability to measure the degree of disability in patients with PD in daily activities in both ON and OFF medication phases.

Determinants of Functional Independence or Its Loss following Subthalamic Nucleus Stimulation in Parkinson’s Disease

Objective: This study aimed to describe the change in functional status following bilateral subthalamic nucleus stimulation (STN-DBS) in Parkinson’s disease (PD) and to identify predictors of postoperative functional dependence. Methods: We included PD patients with bilateral STN-DBS who had complete Schwab & England Activities of Daily Living (S&E ADL) Scale data at baseline and 6 months after surgery from our prospective registry. Functional dependence was defined as an S&E ADL score of less than 80%. All data were collected from the on-medication state and on-stimulation state (after surgery). Logistic regression analyses were performed to determine the factors predictive of functional dependence after surgery. Results: A total of 196 patients were included. At baseline, 41 patients were functionally dependent and the other 155 were functionally independent. Among the patients with preoperative dependence, 32 (78%) became functionally independent after surgery, and this conversion was associated with a lower baseline axial score (p = 0.012). Among the patients with preoperative independence, 21 (14%) developed postoperative dependence, and this conversion was associated with a higher baseline axial score (p = 0.013) and its smaller improvement (p < 0.001). Female sex (odds ratio [OR] 3.214; 95% confidence interval [CI] 1.210–8.542; p = 0.019) and a higher baseline axial score (OR 1.184; 95% CI 1.056–1.327; p = 0.004) significantly predicted the risk of postoperative functional dependence. Conclusions: We found that functional status following bilateral STN-DBS is closely related to preoperative axial symptoms. When loss of independence is a potential target for STN-DBS, clinicians should take into consideration the severity of axial impairment before surgery.

Increased Intraepidermal Nerve Fiber Degeneration and Impaired Regeneration Relate to Symptoms and Deficits in Parkinson's Disease

Background: Previous studies have shown cutaneous small fiber pathology in patients with Parkinson's disease (PD). These studies have focused on nerve degeneration, but recent reports suggest that nerve regeneration may also be important in PD pathology.Objective: To establish the extent of intraepidermal nerve fiber (IENF) degeneration and regeneration and its relationship to clinical and neurological deficits in Parkinson's disease (PD).Methods: Twenty-three PD patients and 10 age-matched controls underwent skin biopsy and assessment of somatic and autonomic symptoms and deficits. We have assessed Intraepidermal Nerve Fiber Density (IENFD) using standard PGP9.5 staining and GAP-43 to assess Mean Axonal Length (MAL) and Intraepidermal Total Nerve Fiber Length (IETNFL).Results: IENFD (p < 0.0001), MAL (p < 0.0001), IETNFL/Area (p = 0.009), and IETNFL/Length (p = 0.04) were significantly reduced in patients with PD compared to controls. IENFD correlated significantly with disease duration (p = 0.03), cumulative levodopa dose (p = 0.02), Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) (p = 0.01), Schwab and England Activities of Daily Living (ADL) (p = 0.03), NSP (p = 0.03), and 30:15 ratio (p = 0.03). IETNFL/Area correlated with the Autonomic Scale for Outcomes in Parkinson's Disease (SCOPA-AUT) (p = 0.03) and Diabetic Neuropathy Symptom score (DNS) (p = 0.04) and IETNFL/Length correlated with DNS (p = 0.03). MAL correlated with SCOPA-AUT (p = 0.01), DNS (p = 0.02), and DB-HRV (p = 0.02).Conclusion: Increased IENF degeneration and impaired regeneration correlates with somatic and autonomic symptoms and deficits in patients with PD.

Dynamics of the Motor Symptoms of Parkinson’s Disease on the Background of Chronic Bilateral Electrical Stimulation of the Subthalamic Nucleus Using Two Methods to Verify Target Structure

Objectives. To determine the efficacy of electrical stimulation of the subthalamic nucleus using different methods to verify target structure in patients with Parkinson’s disease based on assessment of the dynamics of motor symptoms. Materials and methods. A total of 60 patients with PD with chronic bilateral electrical stimulation of the subthalamic nucleus (ES of the STN) were studied. Multichannel microelectrode recording (MER) was performed during neurostimulation electrode implantation surgery in 30 cases. Intraoperative MER was not performed in 30 cases. The control group consisted of 30 patients with PD who received only conservative medication-based treatment. Patient investigations used the Hoehn and Yahr scale, the Tinetti Balance and Mobility Scale (TBMS), the Unifi ed Parkinson’s Disease Rating Scale (UPDRS), the PDQ-39 quality of life self-assessment scale for Parkinson’s disease, and the Schwab and England Activities of Daily Living (ADL) scale. The levodopa equivalent daily dose (LEDD) was determined individually for each patient. Results and conclusions. ES of the STN was found to be effective when used in combination with MER in terms of effects on the severity of the main motor symptoms, motor complications, gait, and measures of quality of life and the activities of daily living. On the background of ES of the STN, patients of both surgical groups attained significant reductions in LEDD with marked improvements in the control of the motor symptoms of PD; significant decreases in the severity of motor fluctuation (50%) and peak dose iatrogenic dyskinesias (51%) were seen. Measures of quality of life and the activities of daily living while off medication improved significantly in both groups of patients receiving ES of the STN independently of the intraoperative target selection technique (75–100%) as compared with the control group.