Revisiting the impact of REM sleep behavior disorder on motor progression in Parkinson's disease

BackgroundEstimation of progression in Parkinson's disease (PD) is useful to guide clinical decisions and to enable patients to plan and manage their life with PD. Rapid eye movement (REM) sleep behavior disorder (RBD) and REM sleep without atonia (RWA) are recognized as early harbingers of neurodegeneration and may precede motor symptoms by years. However, their impact on motor progression remains elusive.MethodsWe retrospectively analyzed polysomnographic and clinical data of 59 PD patients, grouping them into patients with RBD (n = 15), RWA (n = 22) and those with normal muscle atonia (n = 22). We compared the three groups with regard to motor progression, defined as changes in Unified Parkinson's Disease Rating Scale (UPDRS) III values per year, and selected PD specific characteristics.ResultsMotor disability at first visit and time interval between first and last visits were similar between groups. We observed a significantly faster motor progression in PD patients with RBD and RWA than in those with preserved REM sleep atonia.ConclusionOur findings suggest that impaired muscle atonia during REM sleep might represent a marker of faster motor progression in PD.     

Sleep problems affect quality of life in Parkinson's disease along disease progression

ObjectivesNon-motor symptoms (NMS) frequently impact health-related quality of life (HRQoL) in patients with Parkinson's Disease (PD). Sleep problems represent one of the main NMS complained by PD patients. In this observation study, sleep problems measured by Parkinson's Disease Sleep Scale - 2nd version (PDSS-2), and HRQoL measured by Parkinson's Disease Questionnaire-39 (PDQ39) were quantified in patients with PD ranging from mild to moderate-advanced disease stages, and correlated to motor impairment and anti-PD therapy.MethodsWe included idiopathic PD patients who underwent PDSS-2 and PDQ39. Moreover, we assessed patients' motor symptoms by rating the Unified Parkinson's Disease Rating Scale (UPDRS) - III section (motor examination), patients' PD status following H&Y stage, and levodopa equivalent daily dose (LEDD).ResultsOne-hundred and fifty-four patients with PD were included and distributed for H&Y stage. PDSS-2 and PDQ39 total and sub-items scores significantly increased with the H&Y stage. PDSS-2 total score significantly correlated with PDQ39 total score (γ = 0.63, P < 0.01). Finally, distributing PD patients according to the PDSS-2 cut-off for detecting sleep disturbances, we found in poor sleepers (n = 58) higher PDQ39 scores than good sleepers (n = 89).ConclusionsSleep problems are very common in patients with PD and severely impact on HRQoL. Sleep impairment and low HRQoL occur from the early stages of the disease and deteriorate along disease progression. Further studies investigating sleep and quality of life should be planned for targeting sleep improvement to increase HRQoL and possibly reduce motor impairment.     

REM sleep behavior disorder: Association with motor complications and impulse control disorders in Parkinson's disease

ObjectiveClinical phenotypes such as old age, longer disease duration, motor disability, akineto-rigid type, dementia and hallucinations are known to be associated with REM sleep behavior disorder (RBD) in Parkinson's disease (PD). However, the relationship between motor fluctuations/impulse control and related behaviors (ICRB) and RBD is not clear. We designed this study to elucidate the clinical manifestations associated with RBD to determine the implications of RBD in PD.DesignIn a cross-sectional study, a total of 994 patients with PD were interviewed to determine the presence of RBD and their associated clinical features including motor complications and ICRB.ResultsOf the 944 patients, 578 (61.2%) had clinical RBD. When comparing the clinical features between patients with RBD (RBD group) and without RBD (non-RBD group), older age, longer disease duration, higher Hoehn and Yahr stage (H&Y stage), higher levodopa equivalent daily dose (LEDD), and the existence of wearing off, dyskinesia, freezing, and ICRB, especially punding, were associated with the RBD group compared to the non-RBD group (P < .05 in all). Multivariate analysis showed that motor complications including wearing off, peak dose dyskinesia, and diphasic dyskinesia were the only relevant factors for RBD after adjusting for age and disease duration.ConclusionMotor complications and ICRB are more frequent in patients with RBD than in patients without RBD. In addition, motor complications are related to RBD even after adjusting for age and disease duration.     

Investigating rapid eye movement sleep without atonia in Parkinson's disease using the rapid eye movement sleep behavior disorder screening questionnaire

Rapid eye movement (REM) sleep behavior disorder (RBD) is frequently observed in patients with Parkinson's disease (PD). Accurate diagnosis is essential for managing this condition. Furthermore, the emergence of idiopathic RBD in later life can represent a premotor feature, heralding the development of PD. Reliable, accurate methods for identifying RBD may offer a window for early intervention. This study sought to identify whether the RBD screening questionnaire (RBDSQ) and three questionnaires focused on dream enactment were able to correctly identify patients with REM without atonia (RWA), the neurophysiological hallmark of RBD. Forty‐six patients with PD underwent neurological and sleep assessment in addition to completing the RBDSQ, the RBD single question (RBD1Q), and the Mayo Sleep Questionnaire (MSQ). The REM atonia index was derived for all participants as an objective measure of RWA. Patients identified to be RBD positive on the RBDSQ did not show increased RWA on polysomnography (80% sensitivity and 55% specificity). However, patients positive for RBD on questionnaires specific to dream enactment correctly identified higher degrees of RWA and improved the diagnostic accuracy of these questionnaires. This study suggests that the RBDSQ does not accurately identify RWA, essential for diagnosing RBD in PD. Furthermore, the results suggest that self‐report measures of RBD need to focus questions on dream enactment behavior to better identify RWA and RBD. Further studies are needed to develop accurate determination and quantification of RWA in RBD to improve management of patients with PD in the future. © 2014 International Parkinson and Movement Disorder Society     

Rest energy expenditure in Parkinson's disease: Role of disease progression and dopaminergic therapy

BackgroundWeight loss affects more than 50% of subjects suffering from Parkinson's Disease (PD) and is associated with reduced life expectancy. The pathogenesis is multifactorial and the mechanism of PD metabolism control is unresolved. This cross-sectional study aimed to ascertain the relationship between rest energy expenditure (REE), PD duration, Hoehn & Yahr (H&Y) stage, drug therapy and body mass index (BMI), in order to determine possible predictors of weight loss.MethodsWe studied fifty-eight PD subjects, after excluding conditions with a known influence on metabolism and weight (severe tremor, dyskinesias, dementia, fever, on-going infections, thyroid disease, and dysphagia). Subjects underwent REE measurement, through indirect calorimetry, in both the OFF state (12 h fasting and off medications) and in the ON state (60 min after taking dopaminergic drugs).ResultsOFF state. In the majority of PD patients REE values did not differ from those expected (based upon age, gender and BMI), being significantly higher in subjects in H&Y stage IV than H&Y stage II (t = 3.5; p = 0.001). Disease duration and rigidity were significantly associated with increased REE (r² = 0.31, F = 3.6; p = 0.0045). ON state. REE decreased by approximately 8% in all subjects, irrespective of disease duration or H&Y stage. BMI was inversely related to disease duration and UPDRS motor score in the OFF state and directly related to UPDRS motor score in the ON state (r² = 0.333, F = 3.5; p = 0.003).ConclusionsIn PD REE increases as a function of disease duration; its adverse role in the decrease in BMI seems to be compensated for by dopaminergic medication.     

Long-duration Parkinson's disease: Role of lateralization of motor features

BackgroundA mean of 10 years elapse before patients with Parkinson's disease (PD) reach Hoehn & Yahr (H&Y) stage 4, and 14 years for stage 5. A small proportion of PD patients survive and are ambulatory for ≥20 years. We sought to identify features associated with long-duration PD (dPD).MethodsThis five-center, case–control study compared 136 PD patients with ≥20 years of duration and H&Y stage ≤4 (dPD) to 134 H&Y-, age- and gender-matched PD patients between 10 and 15 years of disease (cPD).ResultsBy study design, there were no between-group differences in age, gender and H&Y. dPD subjects were younger at onset (p < 0.0001), had more psychosis (p: 0.038), were receiving higher levodopa equivalent daily doses (p: 0.02), were predominantly left-handed (p: 0.048), and had greater frequency of left-sided onset (p: 0.015) compared to cPD subjects. Both groups had similar rates of resting tremor, dementia and REM sleep behavior disorder.ConclusionsEarly disease onset, left-handedness and left-sided onset are associated with long disease and ambulatory PD survival. The neurobiological basis of the prognostic value of lateralization deserves further investigation.     

REM sleep behavior disorder and motor dysfunction in Parkinson's disease – A longitudinal study

ObjectivesLongitudinal assessment of a Parkinson's disease (PD) cohort, to investigate the evolution or REM sleep behavior symptoms (RBD) over time and to test the relation between RBD at onset and motor dysfunction progression.MethodsAn early stage PD cohort (n = 61) was assessed at two time points, separated by a two years interval. Diagnostic criteria for RBD were: violent behavior during sleep and body movements or vocalization indicative of dream enacting and at least six affirmative answers in the REM sleep behavior disorder screening questionnaire. Motor function assessment was performed with the Unified Parkinson's Disease Scale part II and III (total and partial scores for tremor, bradykinesia, rigidity, gait/postural instability and dysarthria).Results25 Patients had RBD at baseline, vs. 35 at follow-up. Three RBD changed to non-RBD at follow-up, while 10 non-RBD patients developed RBD at follow-up (annual incidence of 12.5%). RBD and non-RBD patients did not differ significantly at baseline or follow-up. The presence of RBD at baseline was significantly related to an increase in UPDRS total and bradykinesia scores over time.DiscussionRBD symptoms can vary over time and have a tendency to increase during the early stages of disease. The presence of RBD symptoms could be a risk factor for motor function deterioration and particularly for bradykinesia worsening.     

Loss of REM sleep features across nighttime in REM sleep behavior disorder

ObjectivesMelatonin is a chronobiotic treatment which also alleviates rapid eye movement (REM) sleep behavior disorder (RBD). Because the mechanisms of this benefit are unclear, we evaluated the clock-dependent REM sleep characteristics in patients with RBD, whether idiopathic (iRBD) or associated with Parkinson's Disease (PD), and we compared findings with PD patients without RBD and with healthy subjects.MethodsAn overnight videopolysomnography was performed in ten iRBD patients, ten PD patients with RBD (PD + RBD+), ten PD patients without RBD (PD + RBD−), and ten controls. The rapid eye movement frequency per minute (REMs index), the tonic and phasic electromyographic (EMG) activity of the levator menti muscle, and the duration of each REM sleep episode were evaluated. A generalized linear model was applied in each group, with the REM sleep cycle (four ordinal levels) as the dependent variable, as a function of REMs index, REM sleep duration, and tonic and phasic EMG activity.ResultsFrom the first to the fourth sleep cycle, REM sleep duration progressively increased in controls only, REMs index increased in subjects without RBD but not in patients with RBD, whether idiopathic or associated with PD, whereas tonic and phasic EMG activity did not change.ConclusionsPatients with PD or iRBD lost the physiologic nocturnal increase in REM sleep duration, and patients with RBD (either with or without PD) lost the increase of REMs frequency across the night, suggesting an alteration in the circadian system in RBD. This supports the hypothesis of a direct effect of melatonin on RBD symptoms by its chronobiotic activity.     

Factors associated with the effect of pramipexole on symptoms of idiopathic REM sleep behavior disorder

BackgroundThe clinical effectiveness of pramipexole (PPX), a candidate treatment for idiopathic rapid eye movement sleep behavior disorder (iRBD), varies among individuals. This study investigates factors associated with PPX effectiveness for treating RBD symptoms.MethodsNinety-eight consecutive patients with RBD who had taken PPX or clonazepam (CNZP) for more than three months were enrolled. Factors associated with PPX effectiveness were examined: the ratio of REM sleep without atonia to total REM sleep (RWA/REM), length of RBD morbidity, frequency of vocalization or abnormal behavior, and Sniffin' Stick Test scores. These factors were also compared among the responders to PPX monotherapy, CNZP monotherapy, and PPX + CNZP combined therapy.ResultsPPX was efficacious in 61.7% (50/81) of the subject patients. RWA/REM was associated with PPX effectiveness. The cut-off rate of RWA/REM for predicting PPX effectiveness was estimated as 16.8%. Responders to PPX + CNZP combined therapy showed significantly higher RWA/REM and frequency of vocalization or dream enactment behavior than either responders to monotherapy with PPX or to CNZP.ConclusionPPX is probably applicable as an alternative to CNZP, especially for mild iRBD cases with a lower rate of RWA. Results of this study suggest that dopaminergic dysfunction can play a role in iRBD pathophysiology.     

Surface EMG activity during REM sleep in Parkinson's disease correlates with disease severity

ObjectivesOver 40% of individuals with Parkinson's disease (PD) have rapid eye movement sleep behavior disorder (RBD). This is associated with excessive sustained (tonic) or intermittent (phasic) muscle activity instead of the muscle atonia normally seen during REM sleep. We examined characteristics of manually-quantitated surface EMG activity in PD to ascertain whether the extent of muscle activity during REM sleep is associated with specific clinical features and measures of disease severity.MethodsIn a convenience sample of outpatients with idiopathic PD, REM sleep behavior disorder was diagnosed based on clinical history and polysomnogram, and severity was measured using the RBD sleep questionnaire. Surface EMG activity in the mentalis, extensor muscle group of the forearms, and anterior tibialis was manually quantitated. Percentage of REM time with excessive tonic or phasic muscle activity was calculated and compared across PD and RBD characteristics.ResultsAmong 65 patients, 31 had confirmed RBD. In univariate analyses, higher amounts of surface EMG activity were associated with longer PD disease duration (srho = 0.34; p = 0.006) and greater disease severity (p < 0.001). In a multivariate regression model, surface EMG activity was significantly associated with RBD severity (p < 0.001) after adjustment for age, PD disease duration, PD severity and co-morbid sleep abnormalities.ConclusionSurface EMG activity during REM sleep was associated with severity of both PD and RBD. This measure may be useful as a PD biomarker and, if confirmed, may aid in determining which PD patients warrant treatment for their dream enactment to reduce risk of injury.     

NREM sleep arousal-related disorders reflect cognitive impairment in Parkinson's disease

BackgroundSleep disorders and cognitive impairment are frequently reported in Parkinson's disease (PD) as non-motor disabling symptoms. While it is known that REM sleep Behaviour Disorder (RBD) in PD is associated with motor and cognitive decline, little is known about the neurobiological significance of NREM sleep arousal-related disorders.Objectives: to evaluate the cognitive and clinical correlates of arousal-related disorders in PD.MethodsClinical data and video-polysomnography were analysed from one hundred-seventy consecutive subjects with PD. Based on the neuropsychological assessment, the subjects were divided into three groups: no cognitive impairment (PD; n = 58), mild cognitive impairment (PD-MCI; n = 58) and overt dementia (PDD; n = 54).ResultsArousal-related disorders by history were reported in 32.9% of the subjects: 10.3% PD, 31.6% PD-MCI and 59.3% PDD (p = 0.001). Video-PSG captured arousal-related disorders in 1.7% PD, 21.2% MCI-PD and 35.6% PDD (p = 0.001). Arousal-related disorders and RBD were recorded in the same night in 7.7% PD, 9.8% MCI-PD and 15.6% PDD (p = 0.04). Patients with arousal-related disorders captured at V-PSG have a longer disease duration (p = 0.003), higher UPDRS score (p = 0.039), longer duration of treatment with levodopa (p = 0.017) and dopamine agonists (p = 0.018), worse H&Y staging (p = 0.001), lower MMSE score (p = 0.019) and more frequently hallucinations (p = 0.004). In multivariate analysis, cognitive impairment significantly increases the risk of arousal-related disorders (OR 3.387–95% CI 1.395–8.220, p = 0.007).ConclusionArousal-related disorders appear to be a marker of cognitive decline in PD. Recognizing arousal-related disorders should make clinicians aware of a possible cognitive decline in PD and eventually modify the therapeutic approach.     

Profile of levodopa-induced dyskinesia in patients of Parkinson’s disease: a record based study

Abstract

Objectives:

Levodopa-induced dyskinesia (LID) is one of the most disabling complications of long-term pharmacotherapy of Parkinson’s disease (PD). The objective of our study was to examine the clinical profile and determinants of severity of LID in Indian PD patients on levodopa therapy.

Methods:

Retrospective analysis of records of PD patients with LID was performed. All patients were on levodopa and carbidopa combination. Records of subjects with complete information about disease profile, drug intake, and dyskinesia were analyzed. Characterization of LID was based on responses to part IV of unified Parkinson's disease rating scale (UPDRS).

Results:

Records of 42 patients (M∶F = 4·6∶1) were analyzed. The median Hoehn and Yahr (H&Y) stage was 2·5 while median duration of levodopa therapy was 6·16 years (range: 1·91–14·58). Early morning dystonia was reported by 97·6% of the patients. Patients treated with ≧2 concomitant PD medication reported a significantly lower median UPDRS IV A score compared to patients treated with <2 number of concomitant drugs. A trend toward a lower UPDRS IV A score was associated with use of dopamine agonists (DA). Patients with H&Y score ≧3 had a significantly higher median total UPDRS IV A score than patients with H&Y score <3.

Discussion:

Early morning dystonia might be more common among Indian patients of LID. Use of a higher number of concomitant PD medications alongside levodopa is associated with a reduced severity of dyskinesia, even on prolonged use. Levodopa-induced dyskinesia is not only a drug-related phenomenon but the stage of PD itself also affects the dyskinesia severity.     

Does REM sleep behavior disorder change in the progression of Parkinson’s disease?

Objectives/backgroundRapid eye movement (REM) Sleep Behavior Disorder (RBD) in Parkinson's disease (PD) may be associated with a malignant phenotype. Despite its prognostic value, little is known about the time course of RBD in PD. In this study, we aimed to ascertain whether or not RBD is a stable feature in PD. In this study, we prospectively evaluated clinical and neurophysiological features of RBD, including REM Sleep Without Atonia (RSWA), in PD patients with RBD at baseline and after three years then assessed whether the changes in measures of RSWA parallel the progression of PD.Patients/methodsIn sum, 22 (17M, mean age 64.0 ± 6.9 years) moderate-to-advanced PD patients (mean PD duration at baseline:7.6±4.8 years) with RBD, underwent a video-polysomnography (vPSG) recording and clinical and neuropsychological assessment at baseline and after three years.ResultsAt follow-up, the self-assessed frequency of RBD symptoms increased in six patients, decreased in six and remained stable in 10, while RSWA measures significantly increased in all subjects. At follow-up, patients showed worse H&Y stage (p = 0.02), higher dopaminergic doses (p = 0.05) and they performed significantly worse in phonetic and semantic fluency tests (p = 0.02; p = 0.04). Changes in RSWA correlated significantly with the severity in levodopa-induced dyskinesia (r = 0.61,p = 0.05) and motor fluctuation (r = 0.54,p = 0.03) scores, and with the worsening of executive functions (r = 0.78,p = 0.001) and visuo-spatial perception (r = −0.57,p = 0.04).ConclusionDespite the subjective improvement of RBD symptoms in one-fourth of PD patients, all RSWA measures increased significantly at follow-up, and their changes correlated with the clinical evolution of motor and non-motor symptoms. RBD is a long-lasting feature in PD and RSWA is a marker of the disease's progression.     

Polysomnographic predictors of sleep,motor and cognitive dysfunction progression in Parkinson's disease: a longitudinal study

ObjectiveTo assess the predictive value of polysomnographic (PSG) data in the prospective assessment of cognitive, motor, daytime and nighttime sleep dysfunction in Parkinson's Disease (PD) patients.MethodsPD patients were assessed at baseline with video-PSG and with cognitive (MoCA), Sleep (SCOPA-Sleep Nighttime and Daytime scores) and Motor (UPDRSIII) function scales at both baseline and four years later. Linear regression analysis was used to assess the relation between PSG variables at baseline and change in symptoms scores.ResultsWe included a total of 25 patients, 12 with rapid eye movement (REM) sleep behavior disorder (RBD) (in 8 PSG was inconclusive, due to lack of REM sleep). MoCA scores decreased significantly at follow-up, while SCOPA-Sleep Daytime and SCOPA-Sleep Nighttime and UPDRSIII did not vary. Lower N3 percentage at baseline was significantly associated with MoCA decrease. Higher Periodic Limb Movements in Sleep index (PLMS) and the presence of RBD were significantly associated with SCOPA daytime score increase. Higher global severity of RBD, tonic RSWA and total number of motor events during REM sleep were associated with SCOPA Nighttime score increase.ConclusionsThe present work suggests that PSG data could be useful for predicting PD cognitive and sleep dysfunction progression. Reduced SWS could predict deterioration of cognitive function, while baseline PLMS could be useful to predict worsening of daytime sleep dysfunction. Severity of RBD could be used for estimating nighttime sleep symptoms progression.     

Relationship between I-MIBG scintigrams and REM sleep behavior disorder in Parkinson’s disease

BackgroundUptake of ¹²³I-labeled meta-iodobenzylguanidine (MIBG) in myocardial scintigrams has been shown to be as low in patients with idiopathic RBD as in Parkinson’s disease (PD) patients.Aim for studyTo clarify whether the existence of RBD accelerates autonomic dysfunction in PD, we investigated the association between MIBG scintigraphic findings and RBD measures among non-dementia PD patients.Subjects &; methodsWe conducted clinical interviews to assess REM sleep behavior disorder (RBD) symptoms, and performed polysomnograms (PSG) recordings and MIBG scintigrams on 49 PD patients. The patients were divided into three groups (PD with clinical RBD, PD with subclinical RBD, and PD with normal REM sleep).ResultsPD patients with clinical RBD had reduced MIBG uptake as determined by heart-to-mediastinum ratios of the delayed image compared to those with subclinical RBD and those with normal REM sleep. Multiple linear regression analysis revealed that only the existence of RBD symptoms was significantly associated with reduced MIBG uptake among PD patients without dementia after adjusting for demographic and PD symptom-related variables.ConclusionPD patients with clinical RBD might suffer from a wider α-synuclein pathology, including reduced cardiac sympathetic ganglia function as reflected by a lowered MIBG uptake.     

Parasomnia as an occasion for the diagnosis of Parkinson's disease.

We report a case of Parkinson's disease (PD) diagnosed by REM sleep behavior disorder (RBD). The patient was a 68-year-old man. On admission, rigidity in the left upper and lower extremities, bradykinesia, and gait disturbance were noted. In addition, polysomnography revealed REM sleep without atonia (RWA), and a diagnosis of untreated PD associated with RBD was made. Polysomnographic data showed that REM density decreased and RWA tended to increase after administration of a combination of L-DOPA and DCI (L-DOPA/DCI). Thus, we considered that the pathophysiological mechanism of RBD in this case was based not only on the dysfunction of the brainstem mechanism of RWA, but also on the impairment of dopaminergic neuron.     

Clinical manifestations of Parkinson disease and the onset of rapid eye movement sleep behavior disorder

ObjectiveTo identify whether the presence and/or timing of rapid eye movement (REM) sleep behavior disorder (RBD) onset were associated with differences in clinical features and sleep parameters of Parkinson disease (PD).MethodsIn all, 112 PD patients were enrolled and all underwent extensive clinical evaluations and video-polysomnography (PSG). Clinical features and PSG parameters were compared in PD patients with (PD + RBD) or without (PD − RBD) RBD, RBD preceding (RBD > PD), or not (PD ⩾ RBD) PD onset.ResultsSixty-three of the 112 PD patients were affected by RBD. Adjusted for age, gender, education, body mass index (BMI), levodopa equivalent daily dose (LED) and PD duration, PD + RBD patients had higher Hoehn & Yahr stage, higher scores for UPDRS parts I, II and III, more dyskinesia, higher ratio of axial/limb manifestations, and more hallucinations. Their cognitive and quality-of-life status was significantly lower (all P < 0.05). For PSG, PD + RBD patients exhibited higher percentages of phasic and tonic EMG activities, lower apnea hypopnea (AHI) and oxygen desaturation index (ODI), and less time in arterial oxygen saturation (SaO₂) <90% during REM sleep (all P < 0.05). PD ⩾ RBD (n = 22) patients did not significantly differ from RBD > PD (n = 41) patients in clinical manifestations, whereas the PD ⩾ RBD subgroup had significantly higher UPDRS part I score, lower PDQ score and lower AHI during REM than the PD − RBD group (all P < 0.05), but not RBD > PD subgroup. Correlation analysis showed that worse cognition was associated with shorter interval of RBD preceding PD onset (r = 0.297, P = 0.018), but not RBD duration (P = 0.202).ConclusionsClinical manifestations of PD may vary depending on the presence and timing of RBD onset. These findings are compatible with the hypothesis that RBD may be a marker of complex subtypes of PD.     

Is serum uric acid related to non-motor symptoms in de-novo Parkinson's disease patients?

BackgroundLow serum uric acid (UA) has been consistently shown to be associated with increased risk of Parkinson's disease (PD), and to predict faster motor and cognitive decline in established PD. The aim of the present study is to evaluate the relationship between serum UA and non-motor symptoms (NMS) in de novo PD.MethodsSerum UA was measured in consecutively recruited, early drug-naïve PD patients. Exclusion criteria were: treatment with UA modifying drugs; current smoking status; metabolic or cardiac morbidity. All patients completed the NMS Questionnaire (NMSQuest). The relationship between UA levels and NMSQuest domains was explored by logistic regression, subsequently adjusted for age, gender, disease duration (months since reported motor onset) UPDRS part III, H&Y scale, and MMSE. Regression analysis studied the overall relationship between UA levels and total NMS score, and was subsequently adjusted for age, gender, disease duration UPDRS part III, H&Y scale and MMSE.ResultsEighty PD patients were recruited. At logistic regression, higher UA levels were related to lower involvement of Attention/Memory (p = 0.004), Cardiovascular (0.009) and Sleep (p = 0.028) domains of NMSQuest. UA levels showed a significant negative correlation with total NMSQuest score at regression analysis (p = 0.001; Adjusted R-squared = 0.319).DiscussionThe present study investigated, for the first time, the relationship between NMSQuest and UA in de novo PD. Lower UA was related to higher NMSQuest total score and in particular to Attention/Memory, Cardiovascular and Sleep domains. Thus, UA seems to be a major candidate to be a valuable biomarker of such early features of PD as NMS.     

A data-driven system to identify REM sleep behavior disorder and to predict its progression from the prodromal stage in Parkinson's disease

ObjectivesTo investigate electroencephalographic (EEG), electrooculographic (EOG) and micro-sleep abnormalities associated with rapid eye movement (REM) sleep behavior disorder (RBD) and REM behavioral events (RBEs) in Parkinson's disease (PD).MethodsWe developed an automated system using only EEG and EOG signals. First, automatic macro- (30-s epochs) and micro-sleep (5-s mini-epochs) staging was performed. Features describing micro-sleep structure, EEG spectral content, EEG coherence, EEG complexity, and EOG energy were derived. All features were input to an ensemble of random forests, giving as outputs the probabilities of having RBD or not (P (RBD) and P (nonRBD), respectively). A patient was classified as having RBD if P (RBD)≥P (nonRBD). The system was applied to 107 de novo PD patients: 54 had normal REM sleep (PDnonRBD), 26 had RBD (PD + RBD), and 27 had at least two RBEs without meeting electromyographic RBD cut-off (PD + RBE). Sleep diagnoses were made with video-polysomnography (v-PSG).ResultsConsidering PDnonRBD and PD + RBD patients only, the system identified RBD with accuracy, sensitivity, and specificity over 80%. Among the features, micro-sleep instability had the highest importance for RBD identification. Considering PD + RBE patients, the ones who developed definite RBD after two years had significantly higher values of P (RBD) at baseline compared to the ones who did not. The former were distinguished from the latter with sensitivity and specificity over 75%.ConclusionsOur method identifies RBD in PD patients using only EEG and EOG signals. Micro-sleep instability could be a biomarker for RBD and for proximity of conversion from RBEs, as prodromal RBD, to definite RBD in PD patients.