Non-motor Symptoms Burden Research Articles

Rock Steady Boxing (RSB) participants with Parkinson’s disease have better quality of life and lower burden of non-motor symptoms than non-participants (1210)

Rock Steady Boxing (RSB) participants with Parkinson’s disease have better quality of life and lower burden of non-motor symptoms than non-participants (1210)

5-2-1 Criteria: A Simple Screening Tool for Identifying Advanced PD Patients Who Need an Optimization of Parkinson's Treatment.

Objective 5- (5 times oral levodopa tablet taken/day) 2- (2 hours of OFF time/day) 1- (1 hour/day of troublesome dyskinesia) criteria have been proposed by a Delphi expert consensus panel for diagnosing advanced Parkinson's disease (PD). The aim of the present study is to compare quality of life (QoL) in PD patients with “5-2-1 positive criteria” vs QoL in PD patients without “5-2-1 positive criteria” (defined as meeting ≥1 of the criteria). Methods This is a cross-sectional, observational, monocenter study. Three different instruments were used to assess QoL: the 39-Item Parkinson's Disease Quality of Life Questionnaire Summary Index Score (PDQ-39SI); a subjective rating of perceived QoL (PQ-10); and the EUROHIS-QOL 8-Item Index (EUROHIS-QOL8). Results From a cohort of 102 PD patients (65.4 ± 8.2 years old, 53.9% males; disease duration 4.7 ± 4.5 years), 20 (19.6%) presented positive 5-2-1 criteria: 6.9% for 5, 17.6% for 2, and 4.9% for 1. 37.5% (12/32) and 25% (5/20) of patients with motor complications and dyskinesia, respectively, presented 5-2-1 negative criteria. Both health-related (PDQ-39SI, 25.6 ± 14 vs 12.1 ± 9.2; p < 0.0001) and global QoL (PQ-10, 6.1 ± 2 vs 7.1 ± 1.3; p=0.007; EUROHIS-QOL8, 3.5 ± 0.5 vs 3.7 ± 0.4; p=0.034) were worse in patients with 5-2-1 positive criteria. Moreover, nonmotor symptoms burden (Non-Motor Symptoms Scale total score, 64.8 ± 44.8 vs 39.4 ± 35.1; p < 0.0001) and autonomy for activities of daily living (ADLS scale, 73.5 ± 13.1 vs 89.2 ± 9.3; p < 0.0001) were worse in patients with 5-2-1 positive criteria. Patient's principal caregiver's strain (Caregiver Stain Index, 4.3 ± 3 vs 1.5 ± 1.6; p < 0.0001), burden (Zarit Caregiver Burden Inventory, 28.4 ± 12.5 vs 10.9 ± 9.8; p < 0.0001), and mood (Beck Depression Inventory II, 12.2 ± 7.2 vs 6.2 ± 6.1; p < 0.0001) were worse in patients with 5-2-1 positive criteria as well. Conclusions QoL is worse in patients meeting ≥1 of the 5-2-1 criteria. This group of patients and their caregivers are more affected as a whole. These criteria could be useful for identifying patients in which it is necessary to optimize Parkinson's treatment.

Executive Function Is Related to the Urinary Urgency in Non-demented Patients With Parkinson's Disease.

Introduction: Evidence suggests urinary urgency is associated with cognitive impairment in a subtype of Parkinson’s disease (PD) patients. This study investigates if cognitive impairment independently predicts the presence of urinary dysfunction.Methods: We report data of 189 idiopathic PD patients, excluding those with concomitant diseases or medication interacting with bladder function. A standardized questionnaire was used to define the presence of urinary urgency. All patients underwent a comprehensive motor, cognitive non-motor and health-related quality of life (HRQoL) assessment. Multivariable linear regression analysis was performed to identify independent variables characterizing urinary urgency in PD (PD-UU), which were assigned as discriminant features to estimate their individual contribution to the phenotype of the PD-UU group.Results: Of 189 PD patients, 115 (60.8%) reported PD-UU. The linear regression analysis showed that among cognitive domains, executive function (EF; p = 0.04) had a significant negative association with PD-UU. In a second model, scores of the Montreal Cognitive Assessment (MoCA) significantly differentiated between study groups (p = 0.007) and also non-motor symptom (NMS) burden (p < 0.001). The third model consisted of reports of HRQoL, of which stigma was the only subscale of the Parkinson’s Disease Questionnaire (PDQ-39) differentiating between patients with and without PD-UU (p = 0.02). The linear discriminant analysis provided evidence that the combination of EF, NMS burden, nocturia, and stigma discriminated between groups with 72.4% accuracy.Conclusion: In our large, non-demented PD cohort, urinary urgency was associated with executive dysfunction (EF), supporting a possible causative link between both symptoms. A combination of neuropsychological and non-motor aspects identified patients with PD-UU with high discriminative accuracy.

Young-onset and late-onset Parkinson's disease exhibit a different profile of fluid biomarkers and clinical features

Young-onset Parkinson's disease (YOPD) is a relevant condition whose neurobiology is questioned if different from those of typical late-onset Parkinson's disease (LOPD). Here, we explored whether the clinical-biochemical profile of Parkinson's disease (PD) could be affected by the age-of-onset (AO), as a possible result of a distinct neurodegenerative process. A panel of fluid biomarkers (CSF lactate, 42-amyloid-β peptide, total and 181-phosphorylated tau; serum uric acid) and the standard scores for motor and nonmotor signs were assessed in 76 idiopathic PD patients (genetic cases excluded; YOPD, AO ≤ 50, n = 44; LOPD, AO > 50, n = 32) and 75 sex/age-matched controls, adjusting the models for the main confounding factors. In PD, AO directly correlated to either CSF lactate and tau proteins or the nonmotor symptoms scale score. Specifically, a younger AO was associated with lower levels of biomarkers and minor burden of nonmotor symptoms. Our findings indicate that clinical-biochemical features of idiopathic PD may vary depending on the AO, accounting for different profiles in YOPD and LOPD whose recognition is fundamental for further pathophysiological implications and clinical applications.

Comparison of Integrated Outpatient Palliative Care With Standard Care in Patients With Parkinson Disease and Related Disorders

Parkinson disease and related disorders (PDRD) have consequences for quality of life (QoL) and are the 14th leading cause of death in the United States. Despite growing interest in palliative care (PC) for persons with PDRD, few studies are available supporting its effectiveness. To determine if outpatient PC is associated with improvements in patient-centered outcomes compared with standard care among patients with PDRD and their caregivers. This randomized clinical trial enrolled participants at 3 academic tertiary care centers between November 1, 2015, and September 30, 2017, and followed them up for 1 year. A total of 584 persons with PDRD were referred to the study. Of those, 351 persons were excluded by phone and 23 were excluded during in-person screenings. Patients were eligible to participate if they had PDRD and moderate to high PC needs. Patients were excluded if they had urgent PC needs, another diagnosis meriting PC, were already receiving PC, or were unable or unwilling to follow the study protocol. Enrolled participants were assigned to receive standard care plus outpatient integrated PC or standard care alone. Data were analyzed between November 1, 2018, and December 9, 2019. Outpatient integrated PC administered by a neurologist, social worker, chaplain, and nurse using PC checklists, with guidance and selective involvement from a palliative medicine specialist. Standard care was provided by a neurologist and a primary care practitioner. The primary outcomes were the differences in patient quality of life (QoL; measured by the Quality of Life in Alzheimer Disease scale) and caregiver burden (measured by the Zarit Burden Interview) between the PC intervention and standard care groups at 6 months. A total of 210 patients with PDRD (135 men [64.3%]; mean [SD] age, 70.1 [8.2] years) and 175 caregivers (128 women [73.1%]; mean [SD] age, 66.1 [11.1] years) were enrolled in the study; 193 participants (91.9%) were white and non-Hispanic. Compared with participants receiving standard care alone at 6 months, participants receiving the PC intervention had better QoL (mean [SD], 0.66 [5.5] improvement vs 0.84 [4.2] worsening; treatment effect estimate, 1.87; 95% CI, 0.47-3.27; P = .009). No significant difference was observed in caregiver burden (mean [SD], 2.3 [5.0] improvement vs 1.2 [5.6] improvement in the standard care group; treatment effect estimate, -1.62; 95% CI, -3.32 to 0.09; P = .06). Other significant differences favoring the PC intervention included nonmotor symptom burden, motor symptom severity, completion of advance directives, caregiver anxiety, and caregiver burden at 12 months. No outcomes favored standard care alone. Secondary analyses suggested that benefits were greater for persons with higher PC needs. Outpatient PC is associated with benefits among patients with PDRD compared with standard care alone. This study supports efforts to integrate PC into PDRD care. The lack of diversity and implementation of PC at experienced centers suggests a need for implementation research in other populations and care settings. ClinicalTrials.gov Identifier: NCT02533921.

Association of the Non-Motor Burden with Patterns of Striatal Dopamine Loss in de novo Parkinson’s Disease

Striatal dopamine deficits play a key role in the pathogenesis of Parkinson's disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

Patient-Reported Prevalence of Non-motor Symptoms Is Low in Adult Patients Suffering From 5q Spinal Muscular Atrophy.

Background: 5q spinal muscular atrophy (SMA) is an autosomal recessive lower motoneuron disease caused by deletion or mutations in the survival motor neuron 1 gene (SMN1) which results in reduced expression of full-length SMN protein. The main symptoms are caused by spinal motor neuron demise leading to muscle atrophy, and medical care mostly refers to motor symptoms. However, new insights of recent studies in severe SMA type I revealed disease involvement of several non-motor regions, for example cardiac, vascular, sensory nerve involvement, and thalamic lesions. Non-motor symptoms (NMS) were previously described in many neurodegenerative diseases i.e., Parkinson's disease and, importantly, also amyotrophic lateral sclerosis.Methods: We screened for NMS in 70 adult patients with SMA type II (SMAII) and type III (SMAIII) and 59 age/sex-matched healthy controls (controls) in a multicenter cross-sectional study including 5 different centers with specialized expertise in medical health care of motoneuron diseases. We used a self-rating questionnaire including 30 different items of gastrointestinal, autonomic, neuropsychiatric, and sleep complaints [NMS questionnaire (NMSQuest)], which is a validated tool in Parkinson's disease.Results: Total NMS burden was low in adult SMA (median: 3 items) and not significantly different compared to controls (median: 2 items). Total NMS of SMA patients did not correlate with disease severity scores. However, the items “swallowing difficulties,” “falling,” and particularly “swelling legs” were significantly more frequently reported in SMA. Neuropsychiatric symptoms were reported in a frequency comparable to controls and were not significantly increased in SMA.Conclusion: Patient-reported prevalence of NMS in adult SMA was low, which does not argue for a clinically relevant multisystemic disorder in SMAII/III. Importantly, adult SMA patients do not seem to suffer more frequently from symptoms of depression or adaptive disorders compared to controls. Our results yield novel information on previously underreported symptoms and will help to improve the medical guidance of these patients.

High ultrasensitive serum C-reactive protein may be related to freezing of gait in Parkinson's disease patients.

C-reactive protein (CRP) is a biomarker of systemic inflammation that has been linked to accelerated decline in walking speed in older adults. The aim of the present study was to compare the CRP levels of PD patients with vs patients without freezing of gait (FOG). Patients and controls participating in the COPPADIS-2015 study that performed blood extraction for determining molecular serum biomarkers were included. Patients with FOG were identified as those with a score of 1 or greater on item-3 of the Freezing of Gait Questionnaire (FOG-Q). Immunoassay was used for determining ultrasensitive CRP (US-CRP) level (mg/dL). In the PD group (n = 225; 61.8 ± 9.5years old, 61.8% males), 32% of the patients presented FOG but none in the control group (n = 65; 60.3 ± 6.1years old, 56.9% males) (p < 0.0001). Differences in US-CRP level were significant in patients with FOG vs patients without FOG and vs controls (0.31 ± 0.52 vs 0.16 ± 0.21 vs 0.21 ± 0.22; p = 0.04). Significant differences were also observed between patients with vs without FOG (p = 0.001) but not between patients and controls (p = 0.163). US-CRP level was related to FOG (OR = 4.369; 95% CI 1.105-17.275; p = 0.036) along with H&Y (OR = 2.974; 95% CI 1.113-7.943; p = 0.030) and non-motor symptoms burden (NMSS total score; OR = 1.017; 95% CI 1.005-1.029; p = 0.006) after adjusting for age, gender, disease duration, equivalent daily levodopa dose, number of non-antiparkinsonian drugs per day, motor fluctuations, cognition, motor phenotype, and chronic use of anti-inflammatory drugs. The present study suggests that serum US-CRP level is related to FOG in PD patients. Inflammation could be linked to FOG development.

Sleep disturbances and gastrointestinal dysfunction are associated with thalamic atrophy in Parkinson\u2019s disease

BackgroundNon-motor symptoms are common aspects of Parkinson’s disease (PD) occurring even at the prodromal stage of the disease and greatly affecting the quality of life. Here, we investigated whether non-motor symptoms burden was associated with cortical thickness and subcortical nuclei volume in PD patients.MethodsWe studied 41 non-demented PD patients. Non-motor symptoms burden was assessed using the Non-Motor Symptoms Scale grading (NMSS). Cortical thickness and subcortical nuclei volume analyses were carried out using Free-Surfer. PD patients were divided into two groups according to the NMSS grading: mild to moderate (NMSS: 0–40) and severe (NMSS: ≥ 41) non-motor symptoms.ResultsThalamic atrophy was associated with higher NMSQ and NMSS total scores. The non-motor symptoms that drove this correlation were sleep/fatigue and gastrointestinal tract dysfunction. We also found that PD patients with severe non-motor symptoms had significant thalamic atrophy compared to the group with mild to moderate non-motor symptoms.ConclusionsOur findings show that greater non-motor symptom burden is associated with thalamic atrophy in PD. Thalamus plays an important role in processing sensory information including visceral afferent from the gastrointestinal tract and in regulating states of sleep and wakefulness.

Levodopa/carbidopa intestinal gel in treatment of non-motor symptoms in advanced Parkinson's disease

To identify the advantages of LCIG in the treatment of NMS among APD patients and appraise the currently available literature to identify the gaps in the available evidence. background:Levodopa is the most commonly used drug for the treatment of motor symptoms of Parkinson's Disease (PD). For managing non-motor symptoms (NMS) in advanced Parkinson's disease (APD), levodopa-carbidopa intestinal gel (LCIG) infusion is preferred over oral levodopa-carbidopa because it bypasses the gastrointestinal tract and overcomes fluctuation and variation in the plasma drug levels. Levodopa is the most commonly used drug for the treatment of motor symptoms of Parkinson's Disease (PD). For managing non-motor symptoms (NMS) in advanced Parkinson's disease (APD), levodopa-carbidopa intestinal gel (LCIG) infusion is preferred over oral levodopa-carbidopa because it bypasses the gastrointestinal tract and overcomes fluctuation and variation in the plasma drug levels. LCIG has been found to be beneficial in improving or relieving various NMS. (central nervous system symptoms, cardiovascular system symptoms, gastrointestinal tract symptoms, systemic symptoms, urinary symptoms, reproductive system symptoms) in patients with APD. LCIG provides an uninterrupted intestinal levodopa infusion by percutaneous endoscopic gastrojejunostomy (PEG-J). It effectively decreases fluctuations in plasma concentrations of levodopa, reduces NMS burden and motor fluctuations in APD, however; adequate dose modification and individualization of therapy are essential for optimal effect.

Validation of a self-completed Dystonia Non-Motor Symptoms Questionnaire.

ObjectiveTo develop and validate a novel 14‐item self‐completed questionnaire (in English and German) enquiring about the presence of non‐motor symptoms (NMS) during the past month in patients with craniocervical dystonia in an international multicenter study.MethodsThe Dystonia Non‐Motor Symptoms Questionnaire (DNMSQuest) covers seven domains including sleep, autonomic symptoms, fatigue, emotional well‐being, stigma, activities of daily living, sensory symptoms. The feasibility and clinimetric attributes were analyzed.ResultsData from 194 patients with CD (65.6% female, mean age 58.96 ± 12.17 years, duration of disease 11.95 ± 9.40 years) and 102 age‐ and sex‐matched healthy controls (66.7% female, mean age 55.67 ± 17.62 years) were collected from centres in Germany and the UK. The median total NMS score in CD patients was 5 (interquartile range 3–7), significantly higher than in healthy controls with 1 (interquartile range 0.75–2.25) (P < 0.001, Mann–Whitney U‐test). Evidence for intercorrelation and convergent validity is shown by moderate to high correlations of total DNMSQuest score with motor symptom severity (TWSTRS: r s = 0.61), clinical global impression (r s = 0.40), and health‐related quality of life measures: CDQ‐24 (r s = 0.74), EQ‐5D index (r s = −0.59), and scale (r s = −0.49) (all P < 0.001). Data quality and acceptability was very satisfactory.InterpretationThe DNMSQuest, a patient self‐completed questionnaire for NMS assessment in CD patients, appears robust, reproducible, and valid in clinical practice showing a tangible impact of NMS on quality of life in CD. As there is no specific, comprehensive, validated tool to assess the burden of NMS in dystonia, the DNMSQuest can bridge this gap and could easily be integrated into clinical practice.

Restless legs syndrome - the under-recognised non-motor burden: a questionnaire-based cohort study

ABSTRACTObjectives: Non-motor symptoms (NMS) range from neuropsychiatric to pain and are an important but underexplored feature of restless legs syndrome (RLS). There are currently no tools available which enable the holistic assessment of NMS in RLS in clinical practice. The primary aim of this study was to systematically assess NMS prevalence and burden in patients with RLS using the NMS Questionnaire (NMSQuest) validated for Parkinson’s disease.Methods: Patients with idiopathic RLS according to the criteria of the international RLS study group (IRLSSG) were included. Patients underwent a physical examination and clinical interview as well as completed the NMS Questionnaire and the international restless legs syndrome study group (IRLSSG) rating scale.Results: Seventy-four patients with primary RLS were included (mean age 64.6 ± 14.4 years, 62.2% female, mean disease duration 23.5 ± 17.8 years, mean Levodopa equivalent daily dose 63.3 ± 67.4 mg). On average patients reported an IRLSSG rating scale score of 24.8 ± 8.2 (maximum 40) and NMSQuest score of 9.9 ± 5.0 (maximum 30). Patients reported a minimum of two NMS with the majority (39.2%) reporting a moderate NMS burden, followed by severe (28.4%) and very severe (17.6%) burden. The most frequent NMS were insomnia (89.2%) followed by nocturia (70.3%), feeling sad (59.5%), forgetfulness (54.1%), urgency (47.3%), feeling anxious (43.2%), unexplained pain (41.9%), difficulty concentrating (40.5%) and dizziness (40.5%). There were no significant differences in NMSQuest total scores according to disease duration and gender (p = 0.739, p = 0.849).Conclusion: In conclusion, this study is one of the first to address NMS in RLS systematically and the data underlines the need to holistically assess NMS in RLS in order to deliver true value-based healthcare for these patients.

Colonic transit, high-resolution anorectal manometry and MRI defecography study of constipation in Parkinson's disease

IntroductionDespite clinical relevance and potential role on the disease pathogenesis, underlying mechanisms of constipation in Parkinson's disease (PD) remain poorly understood. A systematic assessment using complementary physiological investigations was performed to elucidate constipation pathophysiology in order to improve its symptomatic management. MethodsPD patients with constipation were evaluated with clinical questionnaires, colonic transit, high-resolution anorectal manometry and MRI defecography. Results were compared and correlated with clinical features. ResultsA total of 42 patients (69% male; age 68 ± 8 years; disease duration 10.5 ± 6.1 years) were included, of whom 33 (78.6%) had objective constipation defined by < 3 bowel movements per week or straining. Severity of constipation measured by self-administered questionnaires correlated with disease severity, burden of motor and non-motor symptoms but not with age, disease duration or Parkinson's medications. Colonic transit and anorectal function (high-resolution anorectal manometry and/or MRI defecography) was assessed in 15 patients. A combination of both delayed colonic transit and anorectal dysfunction was the pattern most commonly found (60% of patients) and overall anorectal dysfunction was more prevalent than isolated slow transit constipation. Physiological findings were heterogeneous including reduced colonic motility, rectal hyposensitivity, defecatory dyssynergia and poor motor rectal function. ConclusionSubjective constipation in PD is poorly correlated with commonly used definition, assessment questionnaires and physiological results. Multiple complex overlapping pathophysiological mechanisms are responsible including slow transit and anorectal dysfunction. Complementary investigations to assess colonic transit and anorectal function are required in those with refractory symptoms for a systematic assessment and appropriate symptomatic management.

Non-motor symptoms in Parkinson's disease: An explorative network study

Research on the association between non-motor symptoms (NMS) of Parkinson's disease (PD) and patients' quality of life (QoL) has given insight into the burden of NMS. Most studies investigate NMS by assessing the contribution of individual symptoms to QoL. However, symptoms could also have an interactive relationship, which might not be fully taken into account when only studying these individual contributions. Recently, a network approach has been developed that treats symptoms as nodes and associations between symptoms as edges in a network, providing the opportunity to investigate the dimensional spectrum of NMS. In the current cross-sectional study, we investigated NMS with both approaches: first, we assessed individual contributions of NMS to QoL. Second, we aimed to assess NMS using a network approach. Seventy PD patients completed questionnaires on NMS and QoL. Our primary analysis shows that the domains Mood and Pain are significant contributors to QoL. Our secondary network analysis suggests that Mood and Sleep play central roles in the NMS-network, and that Mood and Cognition are strongly related. Because of power issues, the generalizability of our explorative results is limited. However, complementary information from the network analysis does suggest that focusing on sleep problems might help both mood and pain symptoms, which negatively affect QoL. Investigating symptoms not only as individual and independent entities but rather as part of a connected network could show how treating one symptom affects other symptoms.

Non-motor symptoms burden, mood, and gait problems are the most significant factors contributing to a poor quality of life in non-demented Parkinson's disease patients: Results from the COPPADIS Study Cohort

ObjectiveTo identify factors related to a poor health-related and global quality of life (QoL) in a cohort of non-demented Parkinson's disease (PD) patients and compare to a control group. MethodsThe data correspond to the baseline evaluation of the COPPADIS-2015 Study, an observational, 5-year follow-up, multicenter, evaluation study. Three instruments were used to assess QoL: (1) the 39-item Parkinson's disease Questionnaire (PDQ-39), (2) a subjective rating of global QoL (PQ-10), and (3) the EUROHIS-QOL 8-item index (EUROHIS-QOL8). Multiple linear regression methods were used to evaluate the direct impact of different variables on these QoL measures. ResultsQoL was worse in PD patients (n = 692; 62.6 ± 8.9 years old, 60.3% males) than controls (n = 206; 61 ± 8.3 years old, 49.5% males): PDQ-39, 17.1 ± 13.5 vs 4.4 ± 6.3 (p < 0.0001); PQ-10, 7.3 ± 1.6 vs 8.1 ± 1.2 (p < 0.0001); EUROHIS-QOL8, 3.8 ± 0.6 vs 4.2 ± 0.5 (p < 0.0001). A high correlation was observed between PDQ-39 and Non-Motor Symptoms Scale (NMSS) (r = 0.72; p < 0.0001), and PDQ-39 and Beck Depression Inventory-II (BDI-II) (r = 0.65; p < 0.0001). For health-related QoL (PDQ-39), non-motor symptoms burden (NMSS), mood (BDI-II), and gait problems (Freezing Of Gait Questionnaire [FOGQ]) provided the highest contribution to the model (β = 0.32, 0.28, and 0.27, respectively; p < 0.0001); whereas mood and gait problems contributed the most to global QoL (PQ-10, β = -0.46 and −0.21, respectively; EUROHIS-QOL8, β = -0.44 and −0.23, respectively). ConclusionsQoL is worse in PD patients than in controls. Mood, non-motor symptoms burden, and gait problems seem to be the most relevant factors affecting health-related and global perceived QoL in non-demented PD patients.

Motor and non-motor symptoms in blepharospasm: clinical and pathophysiological implications.

Patients with blepharospasm in addition to involuntary contraction of the orbicularis oculi muscle also have non-motor symptoms (psychiatric, sleep, cognitive, and ocular). In this paper, we investigated the relationship of non-motor with motor symptoms and the total burden of non-motor symptoms in patients with blepharospasm. Results were compared with those of age- and sex-matched healthy controls. We enrolled 60 patients with blepharospasm and 40 age-matched healthy controls. In all patients, the severity of blepharospasm was assessed clinically with the Blepharospasm Severity Rating Scale. All the participants underwent a psychiatric, sleep, cognitive, and ocular symptom evaluation. We investigated the correlations between motor, non-motor symptoms, and patients' clinical and demographic features. The frequency of psychiatric, sleep, and cognitive disorders and ocular symptoms was higher in blepharospasm patients than in healthy controls. Non-motor symptoms coexisted in the majority of patients and there was no correlation between non-motor and motor symptoms. The total burden of non-motor symptoms did not associate with motor symptoms and demographic features in blepharospasm. Non-motor symptoms are independent of motor features and likely belong to the clinical spectrum of blepharospasm. The presence of non-motor symptoms possibly reflects a complex network disorder of blepharospasm.

Dysphagia is associated with presynaptic dopaminergic dysfunction and greater non-motor symptom burden in early drug-naïve Parkinson's patients.

BackgroundThe underlying pathophysiology of dysphagia is multifactorial and evidence clarifying the precise mechanisms are scarce. Dysfunction in dopamine-related and non-dopamine-related pathways, changes in cortical networks related with swallowing and peripheral mechanisms have been implicated in the pathogenesis of dysphagia. We aimed at investigating whether dysphagia is associated with presynaptic dopaminergic deficits, faster motor symptom progression and cognitive decline in a population of early drug-naïve patients with Parkinson’s disease.MethodsBy exploring the database of Parkinson’s Progression Markers Initiative we identified forty-nine early drug-naïve Parkinson’s disease patients with dysphagia. Dysphagia was identified with SCOPA-AUT question 1 (answer regularly) and was assessed with MDS-UPDRS Part-II, Item 2.3 (Chewing and Swallowing). We compared Parkinson’s disease patients with dysphagia to Parkinson’s disease patients without dysphagia, and investigated differences in striatal [123I]FP-CIT single photon emission computed tomography levels. Using Cox proportional hazards analyses, we also evaluated whether dysphagia can predict motor deterioration and cognitive dysfunction.ResultsParkinson’s disease patients with dysphagia, harbored a greater deterioration regarding motor and non-motor symptoms and decreased [123I]FP-CIT binding when compared with patients without dysphagia. Higher burden of dysphagia (MDS-UPDRS-II, item 2.3) was correlated with lower [123I]FP-CIT uptakes within the striatum (rs = −0.157; P = 0.002) and the caudate (rs = −0.156; P = 0.002). The presence of dysphagia was not a predictor of motor progression (Hazard ratio [HR]: 1.143, 95% confidence interval [CI]: 0.848–1.541; P = 0.379) or cognitive decline (HR: 1.294, 95% CI: 0.616–2.719; P = 0.496).ConclusionsDysphagia is associated with decreased presynaptic dopaminergic integrity within caudate and greater motor and non-motor symptoms burden in early drug-naïve PD.

Burden of non-motor symptoms in unclear parkinsonism and tremor: A study with [123I]FP-CIT SPECT

BackgroundNon-motor symptoms (NMSs) are clearly more prevalent in Parkinson's disease (PD) patients compared to healthy individuals. However, NMSs are also common in the elderly and other neurological conditions, and thus, it is not known whether NMSs could be used to differentiate PD from parkinsonism/tremor without dopamine deficiency. MethodsWe prospectively evaluated NMSs immediately before brain dopamine transporter (DAT) [123I]FP-CIT SPECT scanning in 193 patients with unclear parkinsonism/tremor. According to the clinical follow-up and imaging results, 84 patients had PD. NMSs and their correlations with striatal DAT binding were investigated in PD patients and in parkinsonism/tremor patients with normal dopamine function. ResultsTotal NMS burden, anxiety or depression did not differ between PD patients and patients with normal DAT binding. DAT-normal patients reported more perception-related (p = 0.045) and attention/memory-related NMSs than PD patients (p < 0.001). Total NMS score did not correlate with striatal DAT binding in either group. ConclusionsIn clinically uncertain cases, the total NMS burden cannot be used as a tool in distinguishing PD patients from patients with non-dopaminergic parkinsonism/tremor. Clinical screening of NMSs appears equally important in all patients with parkinsonism.

COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015): an ongoing global Parkinson's disease project about disease progression with more than 1000 subjects included. Results from the baseline evaluation.

In Parkinson's disease (PD), the course of the disorder is highly variable between patients. Well-designed, prospective studies for identifying PD progression biomarkers are necessary. Our aim was to show the results of baseline evaluations of an ongoing global PD project, COPPADIS-2015 (Cohort of Patients with PArkinson's DIsease in Spain, 2015). This was an observational, descriptive, nationwide study (Spain). The recruitment period ended in October 2017. Baseline evaluation included more than 15 validated scales and complementary studies in a subgroup of participants. In total, 1174 subjects from 35 centres were considered valid for baseline analysis: 694 patients (62.6±8.9years old, 60.3% males), 273 caregivers (58.5±11.9years old, 31.8% males) and 207 controls (61±8.3years old, 49.5% males). The mean disease duration was 5.5±4.4years. Hoehn and Yahr stage was 1 or 2 in 90.7% of the patients whilst 33.9% and 18.1% of them presented motor fluctuations and dyskinesias, respectively. The mean Non-Motor Symptoms Scale total score was 45.4±38.1, and 30.4% of the patients presented cognitive impairment, 16.1% major depression, 12.7% impulse control disorder, 7.2% compulsive behaviour, 57.2% pain and 13.2% falls. Compared to the control group, PD patients presented a significantly higher burden of non-motor symptoms and a worse quality of life. More than 300 subjects conducted complementary studies (serum biomarkers, genetic and neuroimaging). Parkinson's disease is a complex disorder and different non-motor symptoms are frequently present and are more prevalent than in controls. In real clinical practice it is important to ask for them.

Slave to the rhythm: Seasonal differences in non-motor symptoms in Parkinson's disease

IntroductionAlthough circadian variation of (motor) symptoms in Parkinson disease (PD) patients has been described, it remains unclear what effect seasonal variation may have on non-motor symptoms (NMS). MethodsCross-sectional retrospective study on 372 consecutive PD patients taking part in the Non-motor Longitudinal International Study at King's College Hospital London between November 2011 and July 2018. Patients were divided into three groups based on their date of assessment, using a simplified seasonal model: group 1: November–February (n = 107); group 2: March-15 June (n = 107); and group 3: 16 June–October (n = 158). Primary outcome was a seasonal difference in NMS scale (NMSS) total scores (higher scores reflecting greater disability). We hypothesized that PD patients exhibit circannual NMS burden patterns. ResultsAll groups were identical concerning disease onset and duration, HY stage, Levodopa equivalent dose, and gender. There was a seasonal difference in NMSS total scores (p = 0.040), with the highest scores (57.1 ± 42.5) in season 1 (winter months) and the lowest (45.1 ± 34.4) in season 3 (summer months) (p = 0.037). Seasonal differences were observed in NMSS domain 1 (cardiovascular symptoms) (p = 0.011), domain 4 (perceptual problems) (p = 0.017) and domain 9 (miscellaneous symptoms) (p = 0.009). A trend was observed for domain 2 (sleep) (p = 0.057). ConclusionNMS in PD fluctuate throughout the year, with worsening of symptoms in the winter months compared to the summer months suggestive of dysfunction of the body's master clock, the suprachiasmatic nuclei. Such variations must be accommodated in daily care to ascertain appropriate changes in medication regimes and in clinical trials for the interpretation of outcomes.