Prevalence of radicular neuropathic pain in idiopathic Parkinson's disease: A systematic review and meta-analysis.

Parkinson's disease (PD) is estimated to impact up to 1 % of the global population aged 60 years and older. Among the non-motor manifestations of idiopathic PD, radicular neuropathic pain emerges as a noteworthy concern due to its potential for debility in affected individuals. In, this systematic review and meta-analysis we aimed to evaluate the prevalence of radicular neuropathic pain and thus provide evidence of how this painful symptom affects the lives of patients with idiopathic PD. We registered the research protocol for this study in PROSPERO (CRD42022327220). We searched the Embase, Scopus, and PubMed platforms for studies on PD and neuropathic pain until April 2023. The search yielded 36 articles considered to have a low risk of bias. The prevalence of radicular neuropathic pain in patients with PD was 12.7 %, without a difference when we consider the duration of diagnosis (cut-off < 7 years) or levodopa dosage (cut-off <600 mg/dL). Moreover, there was no variation in the prevalence of radicular neuropathic pain regarding a Hoehn and Yahr stage cut-off of <2.5 or >2.5. Of note, a limited number of patients received pain treatment (21.5 %). We also found that the source of publication bias is the use of the Ford criteria (FC), suggesting that this type of diagnostic criteria may contribute to an underdiagnosis of radicular neuropathic pain in patients with PD. This study underlines the necessity for a more discerning and comprehensive approach to the diagnosis and management of radicular neuropathic pain in patients with idiopathic PD.

Assessment of Pulmonary Functions in Parkinson's Disease and Unveiling the Role of Levodopa Therapy: A Cross-Sectional Study.

INTRODUCTION: This investigation aimed to thoroughly characterize the range of pulmonary function abnormalities present in individuals with Parkinson's disease (PD) and to evaluate the effects of levodopa therapy on these respiratory dysfunctions. METHODS:  Ninety-five PD patients diagnosed via the UK Parkinson's Disease Society Brain Bank Diagnostic Criteria were recruited, excluding those with a smoking history or unable to perform pulmonary function tests (PFTs). Severity was assessed using the Hoehn and Yahr Scale. Spirometry-measured PFT parameters (forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow rate (PEFR)) were compared against matched predicted values. The changes in PFT parameters post-levodopa challenge were assessed. RESULTS: Most of the PD patients were aged between 51-60 years, with a mean age of 55.89 ± 8.37 years. Of these, 65.3% were male. A significant proportion of the cohort exhibited restrictive pulmonary patterns (73.7%), while a smaller fraction displayed obstructive (7.4%) or normal (18.9%) pulmonary function patterns. Notably, levodopa treatment correlated with marked improvements in all measured PFT parameters, especially evident in the enhancements from the "off" medication stage to the "on" stage for FVC and FEV1 (P=0.0001). A weak positive correlation between the severity of respiratory restriction and the duration of PD (r = 0.139, P = 0.021) was found, suggesting that PD's progression exerts an increasingly adverse effect on respiratory function over time. CONCLUSION:  The findings of this study illustrate that restrictive pulmonary abnormalities are more prevalent than obstructive patterns in PD patients and that these patients respond favorably to levodopa therapy.

Correlation between 25-hydroxy-vitamin D and Parkinson's disease.

Background: Previous cross-sectional studies have shown that Parkinson's disease (PD) patients have lower serum 25-hydroxyvitamin D (25(OH)D) concentrations than controls. Other studies have not yet tested whether research findings from other regions are generalizable to Chinese populations. In this case-control study, we examined the correlation between 25-hydroxyvitamin D and Parkinson's disease. Methods: We established an association between 25-hydroxyvitamin D deficiency and PD in a case-control study of 100 PD patients and 100 control subjects free of neurological disease at the First Affiliated Hospital of Xinjiang Medical University. Results: Total 25-hydroxyvitamin D levels were deficient in 21 % of patients with PD compared with 4 % of controls. In univariate analyses, plasma levels of 25-hydroxyvitamin D were associated with PD (p < 0.001). In multivariate analyses, vitamin D deficiency (25(OH)D < 20 ng/mL) was significantly associated with PD (p = 0.008, Odds Ratio =17.13, 95 % CI= 2.082-141.075). Individuals with 25(OH)D levels in the lowest quartile had the highest prevalence of PD (p = 0.026, OR=11.786, 95 % CI =1.342-103.51 compared to individuals with values in the highest quartile). Conclusions: Our study reveals an association between 25-hydroxyvitamin D and PD. Patients with incident PD had significantly lower serum 25(OH)D concentrations than age-matched controls. High-risk PD patients with vitamin D deficiency who have not yet developed exercise impairment should undergo vitamin D measurement and any necessary treatment as soon as possible. Limitations of the study: the study needs further assessment of populations with low vitamin D levels in other regions of China; further assessment of the effect of different sources of vitamin D on PD; further study of longitudinal cohorts at different time points.

Analysis of Voice in Parkinson's Disease Utilizing the Acoustic Voice Quality Index.

OBJECTIVES: The purpose of this study was to analyze the acoustic voice quality index (AVQI) in relation to perceptual analysis and disease stage in speakers with Parkinson's disease (PD). STUDY DESIGN: Cross-sectional study. METHODS: The following data were gathered from the Parkinson's Disease Speech corpus of Tampere University (PDSTU): prolonged vowels and reading samples from native Finnish speakers with PD (n = 34), speaker demographic information, and Hoehn and Yahr scale scores. AVQIv03.01 analysis was completed with Praat. Expert raters utilized the GRBASI scale (GRBASI: grade, roughness, breathiness, asthenia, strain, instability) to assess voice quality. AVQI scores were analyzed in relation to GRBASI ratings and disease stage, as measured by the Hoehn and Yahr scale, utilizing correlation analysis. RESULTS: AVQI scores ranged from -0.11 to 4.46 (mean = 1.64, SD = 1.39), GRBASI average total scores ranged from 0-1.83 (mean = 0.66, SD = 0.50), and Hoehn and Yahr scale scores ranged from 1- 4. A statistically significant correlation between AVQI scores and GRBASI ratings was found (rs = 0.508, P = 0.01). Several significant correlations were also found between the parameters of AVQI and scores for G, R, B and A from GRBASI. Hoehn and Yahr scores correlated significantly with GRBASI total score (rs =0.437, P = 0.01) but not with AVQI. CONCLUSION: A significant correlation was found between GRBASI ratings and Hoehn and Yahr scores, but not between AVQI and Hoehn and Yahr scores. DATA AVAILABILITY: Due to the nature of this research, participants of this study did not agree for their data to be shared publicly. Data may be made available on a case-by-case basis. Data will be available after the active phase of the study in 2028.

Depression in Patients With Parkinson's Disease: A Hospital-Based Cross-Sectional Study.

INTRODUCTION: Depression, a common non-motor symptom in Parkinson's disease (PD), is often underdiagnosed and can significantly impact the quality of life (QOL) and treatment outcomes. Specific disease-related factors and non-specific factors may contribute to depression, and these factors should be identified early to plan the appropriate interventions that promote positive mood. The study aimed to assess the prevalence of depression in PD patients and to find out the factors associated with depression among patients with PD attending the neurology OPD of a tertiary care teaching hospital in Trivandrum. METHODS: A cross-sectional study was conducted at the neurology OPD of Government Medical College Hospital, Trivandrum, from December 2021 to February 2023. We included patients with PD diagnosed according to the United Kingdom PD Society Brain Bank criteria. We collected data from 220 patients with PD by interview technique. Hospital Anxiety and Depression Scale (HADS) was used to assess depression and anxiety in this study. Staging and the severity of the motor symptoms were assessed using the Hoehn and Yahr scale and the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS UPDRS Part III), respectively. RESULTS: Among 220 patients with PD, 31.8% (95% CI: 4.36-5.40) had depression. The non-specific variables, such as education, living arrangements, and gender, and disease-specific variables, such as the severity of motor symptoms (MDS UPDRS Part III score) and the Hoehn and Yahr staging of PD, had a statistically significant association with depression. Logistic regression analysis showed that the severity of motor symptoms (OR=2.69, p=0.004)) and female gender (OR=1.830, p= 0.05) were the independent factors associated with depression. CONCLUSION: Depression is a common non-motor symptom of PD that is often underdiagnosed and undertreated and can significantly impact the QOL of patients and their caregivers. Hence, it should be identified early and managed by pharmacological and non-pharmacological strategies.

Shaping the course of early-onset Parkinson's disease: insights from a longitudinal cohort.

INTRODUCTION: Early -onset Parkinson's disease (EOPD) labels those cases with onset earlier than fifty. Although peculiarities emerged either in clinical or pathological features, EOPD is managed alike typical, late-onset PD. A customized approach would be, instead, better appropriate. Accordingly, a deeper characterization of the clinical course, with an estimation of the disease progression rate, the therapy flow, and the main motor and non-motor complications occurrence, is needed. METHODS: A longitudinal cohort of 193 EOPD patients (selected on a single-centre population of 2000 PD cases) was retrospectively analysed, providing descriptive statics on a series of clinical parameters (genetics, phenotype, comorbidities, therapies, motor and non-motor complications, marital and gender issues) and modelling the trajectories from diagnosis to 10 years later of both Hoehn and Yahr (H&Y) stage and levodopa equivalent daily dose (LEDD). RESULTS: EOPD had a prevalence of 9.7%, including few monogenic cases. It mostly appeared as a motor syndrome, with asymmetric, rigid-akinetic presentation. H&Y linearly progressed with an increment of 0.92 points/10 years; LEDD flow had a non-linear trend, increasing of 526.90 mg/day in 0-5 years, and 166.83 mg/day in 5-10 years. Motor fluctuations started 6.5 ± 3.2 years from onset, affecting up to 80% of the cohort. Neuropsychiatric troubles interested the 50%, sexual complaints the 12%. Gender-specific motor disturbances emerged. CONCLUSION: We shaped EOPD course, modelling a "brain-first" PD subtype, slowly progressive, with non-linear dopaminergic requirement. Major burden mostly resulted from motor fluctuations, neuropsychiatric complications, sexual and marital complaints, with a considerable gender-effect.

Non-Motor Symptoms Burden in Early Stages of Parkinson's Disease.

Background: Non-motor symptoms (NMSs) in Parkinson's disease (PD) are often overlooked and thus can impede clinical management and significantly reduce the patient's quality of life. Aims: The study aimed to determine the burden of NMS in the early stages of PD. Material and Methods: A 1-year observational cross-sectional study was conducted at Mayo Hospital, Lahore, in 2019. The MDS-PD criteria were used to diagnose PD patients. The study included patients with Hoehn and Yahr (HY) stages 1-3. The frequency of NMSs was assessed using a non-motor symptom questionnaire (NMSQ), and the non-motor symptom scale (NMSS) score was derived using the NMSS. Results: A total of 100 PD patients were enrolled in the study. Sixty-three (63%) were males and 37 (37%) were females. Their age ranged between 45 and 75 years with a mean ± SD of 57.46 ± 8.46. At least one NMS was reported by 84% of patients, with neuropsychiatric symptoms (68%) preponderant, followed by a change in taste and smell (64%). The mean NMSS score is 46.22 ± 22.098 (median 44) with a range from 0 to 88, with the trend being increasing score with the advancing stage. Conclusion: The use of the NMSQ and NMSS tools should be standard in clinical practice to identify the severity of the disease and commence appropriate care.

Blood neurofilament light chain in Parkinson's disease.

Blood neurofilament light chain (NfL) is an easily accessible, highly sensitive and reliable biomarker for neuroaxonal damage. Currently, its role in Parkinson's disease (PD) remains unclear. Here, we demonstrate that blood NfL can distinguish idiopathic PD from atypical parkinsonian syndromes (APS) with high sensitivity and specificity. In cross-sectional studies, some found significant correlations between blood NfL with motor and cognitive function, whereas others did not. In contrast, prospective studies reported very consistent associations between baseline blood NfL with motor progression and cognitive worsening. Amongst PD subtypes, especially postural instability and gait disorder (PIGD) subtype, symptoms and scores are reliably linked with blood NfL. Different non-motor PD comorbidities have also been associated with high blood NfL levels suggesting that the neuroaxonal damage of the autonomic nervous system as well as serotonergic, cholinergic and noradrenergic neurons is quantifiable. Numerous absolute NfL cutoff levels have been suggested in different cohort studies; however, validation across cohorts remains weak. However, age-adjusted percentiles and intra-individual blood NfL changes might represent more valid and consistent parameters compared with absolute NfL concentrations. In summary, blood NfL has the potential as biomarker in PD patients to be used in clinical practice for prediction of disease severity and especially progression.

Time Taken for and Causes of a Decline to Hoehn and Yahr Stage 5 in Patients with Parkinson's Disease.

Objective Prediction of time until and causes of becoming bedridden may help patients with Parkinson's disease (PD) plan their productive lives. This study assessed the relationship between the age at the PD onset and time taken to reach Hoehn and Yahr stage (HY) 5 as well as the causes of motor decline to HY5 in Japanese patients with PD. Patients We enrolled patients with PD who visited our institute between April 2015 and December 2020, met the UK brain bank criteria, had medical records from the early PD stage, and had had HY5 for over three months. The relationship between the age at the PD onset and the disease duration was evaluated. Data on the possible causes of motor decline to HY5 were obtained from patients, caregivers or medical records. Results In total, 123 patients with PD (mean age at the PD onset was 69.3 years old; 80 women and 43 men) were included. The age at the PD onset was significantly and negatively correlated with the time until the decline to HY5. Among the 123 patients, 49 reported that the natural course of PD caused the decline to HY5. Possible events that accelerated the motor decline to HY5 included traumatic injury, pneumonia, and other medical or social conditions that might have resulted in reduced daily activities. Conclusion The time until the decline to HY5 can be estimated based on the age at the PD onset. In addition to natural PD progression, medical or social conditions that reduce physical activity may accelerate motor decline to HY5.

Can the prediction model using regression with optimal scale improve the power to predict the Parkinson's dementia?

BACKGROUND: Efficiently detecting Parkinson's disease (PD) with dementia (PDD) as soon as possible is an important issue in geriatric medicine. AIM: To develop a model for predicting PDD based on various neuropsychological tests using data from a nationwide survey conducted by the Korean Centers for Disease Control and Prevention and to present baseline data for the early detection of PDD. METHODS: This study comprised 289 patients who were 60 years or older with PD [110 with PDD and 179 Parkinson's Disease-Mild Cognitive Impairment (PD-MCI)]. Regre-ssion with optimal scaling (ROS) was used to identify independent relationships between the neuropsychological test results and PDD. RESULTS: In the ROS analysis, Korean version of mini mental state ex-amination (MMSE) (KOREAN version of MMSE) (b = -0.52, SE = 0.16) and Hoehn and Yahr staging (b = 0.44, SE = 0.19) were significantly effective models for distinguishing PDD from PD-MCI (P < 0.05), even after adjusting for all of the Parkinson's motor symptom and neuropsychological test results. The optimal number of categories (scaling factors) for KOREAN version of MMSE and Hoehn and Yahr Scale was 10 and 7, respectively. CONCLUSION: The results of this study suggest that among the various neuropsychological tests conducted, the optimal classification scores for KOREAN version of MMSE and Hoehn and Yahr Scale could be utilized as an effective screening test for the early discrimination of PDD from PD-MCI.

[Direct medical costs of Parkinson's disease by Hoehn and Yahr severity in Japan: An analysis of administrative claims data].

To estimate the medical costs related to Parkinson's disease (PD) by Hoehn and Yahr (HY) scale, we conducted a descriptive study by using a large-scale hospital based administrative claims database in Japan. Approximately 20,000 PD patients who had a diagnosis of PD with HY severity between April 2008 and December 2018 were included in the analysis. Estimated PD related outpatient costs, frequency of hospitalization, length of stay, and inpatient costs were increased with HY severity. Our estimates of the PD related medical costs are based on the large-scale claims database, despite limitations such as the reliability of HY severity in the claims data, could be used in future cost-effectiveness studies for treatment of PD.

Apathy-Related Symptoms Appear Early in Parkinson's Disease.

BACKGROUND: Apathy, often-unrecognized in Parkinson's Disease (PD), adversely impacts quality-of-life (QOL) and may increase with disease severity. Identifying apathy early can aid treatment and enhance prognoses. Whether feelings related to apathy (e.g., loss of pleasure) are present in mild PD and how apathy and related feelings increase with disease severity is unknown. METHODS: 120 individuals (M age: 69.0 ± 8.2 y) with mild (stages 1-2, n = 71) and moderate (stages 2.5-4; n = 49) PD were assessed for apathy and apathy-related constructs including loss of pleasure, energy, interest in people or activities, and sex. Correlations were used to determine the association of apathy with apathy-related constructs. Regression models, adjusted for age, cognitive status, and transportation, compared groups for prevalence of apathy and apathy-related feelings. RESULTS: Apathy-related constructs and apathy were significantly correlated. Apathy was present in one in five participants with mild PD and doubled in participants with moderate PD. Except for loss of energy, apathy-related constructs were observed in mild PD at a prevalence of 41% or greater. Strong associations were noted between all apathy-related constructs and greater disease severity. After adjustment for transportation status serving as a proxy for independence, stage of disease remained significant only for loss of pleasure and loss of energy. CONCLUSION: People with mild PD showed signs of apathy and apathy-related feelings. Loss of pleasure and energy are apathy-related feelings impacted by disease severity. Clinicians should consider evaluating for feelings related to apathy to enhance early diagnosis in individuals who might otherwise not exhibit psychopathology.

Serum neurofilament light chain and postural instability/gait difficulty (PIGD) subtypes of Parkinson's disease in the MARK-PD study.

The PIGD (postural instability / gait difficulty) subtype of Parkinson´s disease (PD) is associated with faster cognitive and motor decline. So far, there are no quantifiable biomarkers to aid clinical subtyping. Neurofilament light chain (NfL) is a highly specific marker of neuro-axonal damage and can be assessed in blood. Here, we investigated if serum NfL concentrations are associated with PIGD subtype and PIGD scores in PD patients at advanced disease stages. Furthermore, we evaluated if serum NfL is associated with motor and cognitive function assessed with MDS-UPDRS part III and Montreal cognitive assessment (MoCA). Serum NfL levels were analyzed with Single Molecule Assays (Simoa) in blood of 223 PD patients from the bioMARKers in Parkinson's Disease (MARK-PD) study. Serum NfL concentrations were higher in PIGD patients independent of age, sex and disease duration. In linear regression analysis, serum NfL levels were associated with MoCA, MDS-UPDRS III and PIGD scores in unadjusted models, but remained significant after adjustment only with PIGD scores. In conclusion, increased serum NfL levels were associated with PIGD subtype and PIGD scores in patients with advanced PD.

Quantitative evaluation of brain iron accumulation in different stages of Parkinson's disease.

BACKGROUND AND PURPOSE: Excessive brain iron deposition is involved in Parkinson's disease (PD) pathogenesis. However, the correlation of iron accumulation in various brain nuclei is not well-established in different stages of the disease. This cross-sectional study aims to evaluate quantitative susceptibility mapping (QSM) as an imaging technique to measure brain iron accumulation in PD patients in different stages compared to healthy controls. METHODS: Ninety-six PD patients grouped by their Hoehn and Yahr (H&Y) stages and 31 healthy controls were included in this analysis. The magnetic susceptibility values of the substantia nigra (SN), red nucleus (RN), caudate, putamen, and globus pallidus were obtained and compared. RESULTS: Iron level was increased in the SN of PD patients in all stages versus controls (p < .001), with no significant difference within stages. Iron in the RN was significantly increased in stage II versus controls (p = .013) and combined stages III and IV versus controls (p < .001). The iron levels in caudate, putamen, and globus pallidus were not different between any groups. CONCLUSIONS: Our data suggest iron accumulation occurs early in the disease course and only in the SN and RN of these patients. This is a large cross-sectional study of brain iron deposition in PD patients according to H&Y staging. Prospective studies are warranted to further validate QSM as a method to follow brain iron, which could serve as a disease biomarker and a therapeutic target.

Alterations of Regional Homogeneity in the Mild and Moderate Stages of Parkinson's Disease.

Objectives: This study aimed to investigate alterations in regional homogeneity (ReHo) in early Parkinson's disease (PD) at different Hoehn and Yahr (HY) stages and to demonstrate the relationships between altered brain regions and clinical scale scores. Methods: We recruited 75 PD patients, including 43 with mild PD (PD-mild; HY stage: 1.0-1.5) and 32 with moderate PD (PD-moderate; HY stage: 2.0-2.5). We also recruited 37 age- and sex-matched healthy subjects as healthy controls (HC). All subjects underwent neuropsychological assessments and a 3.0 Tesla magnetic resonance scanning. Regional homogeneity of blood oxygen level-dependent (BOLD) signals was used to characterize regional cerebral function. Correlative relationships between mean ReHo values and clinical data were then explored. Results: Compared to the HC group, the PD-mild group exhibited increased ReHo values in the right cerebellum, while the PD-moderate group exhibited increased ReHo values in the bilateral cerebellum, and decreased ReHo values in the right superior temporal gyrus, the right Rolandic operculum, the right postcentral gyrus, and the right precentral gyrus. Reho value of right Pre/Postcentral was negatively correlated with HY stage. Compared to the PD-moderate group, the PD-mild group showed reduced ReHo values in the right superior orbital gyrus and the right rectus, in which the ReHo value was negatively correlated with cognition. Conclusion: The right superior orbital gyrus and right rectus may serve as a differential indicator for mild and moderate PD. Subjects with moderate PD had a greater scope for ReHo alterations in the cortex and compensation in the cerebellum than those with mild PD. PD at HY stages of 2.0-2.5 may already be classified as Braak stages 5 and 6 in terms of pathology. Our study revealed the different patterns of brain function in a resting state in PD at different HY stages and may help to elucidate the neural function and early diagnosis of patients with PD.

Several miRNAs derived from serum extracellular vesicles are potential biomarkers for early diagnosis and progression of Parkinson's disease.

BACKGROUND: Blood-based test for predicting disease progression and early diagnosis of Parkinson's disease (PD) is an unmet need in the clinic. The profiles of microRNAs (miRNAs) are regarded as potential diagnostic biomarkers for human diseases, whereas miRNAs in the periphery are susceptible to the influence of various components. MiRNAs enriched in serum extracellular vesicles (EVs) have demonstrated disease-specific advantages in diagnosis due to their high abundance, stability and resistance to degradation. This study was aimed to screen differentially expressed EV-derived miRNAs between healthy controls and PD patients to aid in diagnosis of PD. METHODS: A total of 31 healthy controls and 72 patients with a diagnosis of PD at different Hoehn and Yahr stages in Tangdu Hospital were included. In total, 185 differentially expressed miRNAs were obtained through RNA sequencing of serum EVs as well as edgeR and t-test analyses. Subsequently, the weighted gene co-expression network analysis (WGCNA) was utilized to identify the commonly expressed miRNAs in all stages of PD by constructing connections between modules, and specifically expressed miRNAs in each stage of PD by functional enrichment analysis. After aligning these miRNAs with PD-related miRNAs in Human miRNA Disease Database, the screened miRNAs were further validated by receiver operating characteristic (ROC) curves and quantitative real-time polymerase chain reaction (qRT-PCR) using peripheral blood EVs from 40 more participants. RESULTS: WGCNA showed that 4 miRNAs were commonly associated with all stages of PD and 13 miRNAs were specifically associated with different stages of PD. Of the 17 obtained miRNAs, 7 were validated by ROC curve analysis and 7 were verified in 40 more participants by qRT-PCR. Six miRNAs were verified by both methods, which included 2 miRNAs that were commonly expressed in all stages of PD and 4 miRNAs that were specifically expressed in different stages of PD. CONCLUSIONS: The 6 serum EV-derived miRNAs, hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-199a-3p, hsa-miR-28-5p, hsa-miR-22-5p and hsa-miR-151a-5p, may potentially be used as biomarkers for PD progression and for early diagnosis of PD in populations.

Parkinson's disease in Sweden-resource use and costs by severity.

OBJECTIVES: To estimate resource use and costs, including direct and indirect costs, in relation to levels of severity in individuals with Parkinson's disease (PD) in a Swedish setting. MATERIALS AND METHODS: Patients with idiopathic PD registered in the National Parkinson's Disease Patient Registry (PARKreg), with registrations of Hoehn and Yahr (H&Y) and "off time" in the Skåne Region, were included. Annual costs of healthcare contacts, drugs, formal and informal care, and productivity loss associated with PD were estimated using data from PARKreg linked with regional and national healthcare registers between 2013 and 2019. RESULTS: In total, 960 patients and 1324 observations (patient-years) were included. Total average cost per patient-year was SEK 168,982 (EUR 15,958) and ranged from SEK 62,404 (EUR 5893) for H&Y stage I to SEK 1,056,324 (EUR 99,755) in H&Y stage V. The dominating part of total costs for early stages were indirect costs accounting for 50-60% while formal care made up for 55% and 81% of total costs in H&Y IV and V, respectively. Total mean costs for formal care, informal care, and productivity loss also increased with increasing off-time. CONCLUSION: Advanced and late stages of PD are associated with significant societal costs as patients in those stages often require resource-intensive and costly formal care. Thus, there are potential savings to be made, by optimizing the pharmacological and surgical symptomatic treatment of patients with advanced disease.

Sphingosine-1-Phosphate, Motor Severity, and Progression in Parkinson's Disease (MARK-PD).

BACKGROUND: Treatment with sphingosine-1-phosphate (S1P) agonists confers neuroprotective effects in animal models of Parkinson's disease (PD). OBJECTIVES: We assessed the association of serum S1P levels with motor and cognitive symptoms in patients with PD. METHODS: S1P concentrations were analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) in serum of 196 PD patients and in 196 age- and sex-matched controls. Motor (Unified Parkinson's disease rating scale III [UPDRS III], Hoehn and Yahr) and cognitive (Montreal Cognitive Assessment [MoCA]) function were assessed at baseline. Follow-up data was available from 64 patients (median [interquartile range], 513 [381-677] days). RESULTS: S1P levels were lower in PD patients compared with controls, that is 1.75 (1.38-2.07) and 1.90 (1.59-2.18) µmol/L, respectively (P = 0.001). In PD patients, lower S1P concentrations were associated with higher UPDRS III scores and Hoehn and Yahr stage. In the follow-up cohort, S1P concentrations below the median were associated with faster motor decline (hazard ratio: 4.78 [95% CI, 1.98, 11.50]), but not with cognitive worsening. CONCLUSIONS: Our observations reveal an association of S1P with PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Prevalence of Non-motor Symptoms in Parkinson's Disease and Its Impact on Quality of Life in Tertiary Care Center in India.

CONTEXT: Parkinson's disease (PD) is a neurodegenerative disease characterized by traditional motor features. Non-motor symptoms (NMS) are also seen in PD, which inevitably emerge through the disease progression and are often under-recognized and untargeted. AIMS: We studied the prevalence of NMS in PD and their impact on health-related quality of life (HRQoL). MATERIALS AND METHODS: A cross-sectional observational study from January 2017 to July 2017 of PD patients (n = 100) was done. NMS and HRQoL are measured using NMS scoring scale; PD questionnaire-39 and Hoehn and Yahr scale, respectively. Motor symptoms were assessed using scales for outcome in Parkinson's disease (SCoPA) - motor scoring scale. STATISTICAL ANALYSIS: Descriptive statistics calculated for NMS' prevalence. Continuous variables were assessed by two-tailed t-test and discrete and categorical variables by chi-square test. Multiple linear regression analysis was done among scoring scales to identify the influence on 39-item Parkinson's disease questionnaire (PDQ-39) scoring scale. All statistical data collected are analyzed with SSPS software version- 20 for windows. RESULTS: In 100 study population, 66 were males and 34 females. The mean age was 68.35 years and median onset of duration of PD was 3.49 with 64.6% on treatment. Fatigue, pain, and lightheadedness were more prevalent NMS with 78%, 75%, and 69%, respectively. With regression analysis, strongest predictor was NMSS score (P = 0.000), with each unit increase, it is associated with nearly 0.65 increase in PDQ-39 score. CONCLUSION: Though motor symptoms define the disease, NMS have a larger impact on HRQoL in PD and on caregiver's life. Understanding the pattern and effect of NMS is needed for targeted treatment strategies.

Autonomic Testing Profiles in Scans without Evidence of Dopaminergic Deficit (SWEDD).

BACKGROUND: Scans without evidence of dopaminergic deficit (SWEDDS) on 123I-FP-CIT SPECT (DAT) can occur in patients with clinical evidence of Parkinsonism. In this patient population, autonomic function testing may elucidate the underlying clinical disorder. OBJECTIVE: To evaluate SWEDD patients undergoing autonomic testing and determine the severity and pattern of autonomic dysfunction. METHODS: All patients with a diagnosis of SWEDD and formal autonomic function testing at Mayo Clinic, MN were retrospectively reviewed. Autonomic failure was quantified using composite autonomic severity score (CASS). The Modified Hoehn and Yahr score (HYS) determined Parkinsonism severity. RESULTS: Of 1,874 patients with DAT imaging at Mayo Clinic, 13 met diagnostic criteria of SWEDD. The median age of symptom onset was 56.0 (IQR 40.5-75.5). Autonomic dysfunction was present in 12/13 on ARS and/or TST. The median CASS was 2.50 (IQR 1.00-3.00). Distal anhidrosis was most common (7/13) while 3/13 had widespread anhidrosis on TST and/or QSART testing. Patients with a distal pattern of anhidrosis had a median score of 3.0 (IQR 2.38-4.25) on the HYS versus 2.0 (IQR 1.00-2.00) for those with a diffuse pattern (p = 0.048). Patients with more advanced Parkinsonism were more likely to respond to L-Dopa, with higher HYS in the dopa-responsive versus non-Dopa-responsive (p = 0.026). No correlation existed between severity of Parkinsonism, and CASS (p = 0.39). CONCLUSION: Autonomic function testing may detect autonomic dysfunction in most patients with SWEDD. The pattern of dysfunction is suggestive of the degree of clinical Parkinsonism, and autonomic testing may predict whether patients with SWEDD respond to L-Dopa.