bluuebunny/crossref_metadata_2025_split huggingface dataset:
0683 Rest-activity Pattern in Isolated RBD – from Prodromal Stage to Association with Parkinsonism-first Phenoconversion
Authors: Zhou Li , Feng Hongliang , Huang Bei , Wang Jing , Tang Shi , Zhang Jihui , Chan Joey , Chau Steven WH , Yu Mandy WM , Mok Vincent CT , Liu Yaping , Wing Yun Kwok 
Published: April 2024

Abstract

Introduction
Previous evidence suggested that the alteration of rest-activity pattern occurred in patients with isolated rapid eye movement behavior disorder (iRBD), a prodromal stage of α-synucleinopathy with implication to future phenoconversion. Nonetheless, it remains unclear whether this rest-activity pattern alteration has already emerged in the prodromal stage of RBD, and whether it would be related to conversion of iRBD into parkinsonism-first or dementia-first subtype of α-synucleinopathy.

Methods
We performed 1) a case-control study to compare the rest-activity pattern measured by 7-day actigraphy among prodromal RBD subjects (n = 21) and their age-, sex-, and body mass index-matched control subjects (n = 52) and patients with iRBD (n = 63); and 2) a longitudinally follow-up study to investigate the predictive value of altered rest-activity pattern to parkinsonism-first or dementia-first subtype of α-synucleinopathy in full sample of patients with iRBD (n = 170). Prodromal RBD subjects were defined as subjects who had recurrent dream-enactment behaviors but with subthreshold REM sleep electromyography activity. Generalized linear model was employed to assess rest-activity pattern in prodromal RBD subjects and competing risk regression model was used to determine the predictive value of rest-activity pattern to RBD phenoconversion.

Results
Similar to patients with iRBD, prodromal RBD subjects had more daytime probable napping (percentage and duration) and lower average weekly activity level and physical activity level during active period as compared to control subjects. Of 170 patients with iRBD, 166 were successfully followed up with a mean follow-up duration of 4.6 years. Lower average weekly activity level, amplitude, and physical activity level during active period were associated with a higher risk of parkinsonism-first subtype of α-synucleinopathy, instead of dementia-first subtype.

Conclusion
Our study found that altered rest-activity pattern has already emerged in prodromal stage of RBD. As for iRBD patients, lower physical activity level and amplitude might serve as predictive markers of parkinsonism-first conversion.

Support (if any)
No
0685 Opioid Treatment of Patients with Painful versus Painless Restless Legs Syndrome
Authors: Karroum Elias , Zackon Jordana , Winkelman John 
Published: April 2024

Abstract

Introduction
Recent studies characterized a clinically more severe and painful (compared to painless) form of restless legs syndrome (RLS). Data comparing pharmacological treatments in patients with painful and painless RLS are scarce. The current study investigated long-term opioid treatment in patients with painful versus painless RLS.

Methods
Data were extracted from the National RLS Opioid Registry, an ongoing observational longitudinal study of adult patients with a confirmed diagnosis of RLS treated with opioids. Painful RLS classification was based on a “Yes/No” response to the question: “Would you consider your RLS to be painful?”. Baseline collected data included age, gender, ethnicity, body mass index, education, RLS family history, age at RLS onset, augmentation history, and International RLS Severity Scale (IRLS). Both RLS concomitant treatments (alpha-two-delta, α2δ) ligands; dopaminergic agents, DA) and RLS opioid treatments with daily dose in morphine milligram equivalents (MME) were collected at baseline and after two years.

Results
Data for 447/500 initially enrolled RLS patients (146 painful and 301 painless RLS) were available after two years. Painful (versus painless) RLS patients were less frequently White (94.5% versus 98.3%; P=0.0347) and had more severe RLS symptoms at baseline (IRLS scores: 16.6±10.0 versus 11.3±9.1; P&lt; 0.0001). Frequency of patients on concomitant DAs or α2δ ligands did not differ between the two subgroups at baseline or after two years. The mean daily opioid dose (MME) did not differ between the two subgroups at baseline or after two years. The frequency of patients with MME ≥50 was higher in the painful RLS subgroup at baseline (27.4% versus 18.6%; P=0.0338) but not after two years. Painful RLS patients either increased or decreased opioid dose (65.1% versus 53.2%; P=0.0170) and more frequently switched, added, or discontinued opioids (25.3% versus 15.6%; P= 0.0135) after two years.

Conclusion
Whether the higher need for change in opioid dose or medication in patients with painful RLS is related to the severity of RLS and/or lack of efficacy remains to be determined.

Support (if any)
The National RLS Opioid Registry received support from the RLS Foundation, Baszucki Group, and Jerry Blakeley.
0686 Systemic Evaluation of REM Without Atonia Associated with Psychotropic Medications
Authors: Araujo Matheus Lima Diniz , Mouchati Christian , Rodriguez Carlos , Foldvary-Schaefer Nancy 
Published: April 2024

Abstract

Introduction
Selective serotonin reuptake inhibitors (SSRIs), Serotonin and norepinephrine reuptake inhibitors (SNRIs), and Tricyclic antidepressants (TCAs) alter REM sleep motor characteristics and have been associated with REM sleep behavior disorder (RBD). We leveraged a large cohort of polysomnograms (PSGs) to analyze the relationship of SSRI, SNRI, and TCA use on REM without atonia (RWA).

Methods
We analyzed 1075 PSGs from the Cleveland Clinic Starlit Registry with &gt;10% total sleep time in REM sleep systematically scored for RWA using AASM 2.6 criteria. Percent of REM epochs meeting RWA criteria in PSGs without medication use were compared with the following medication groups: SSRI (N=303), SNRI (N=142), TCA (N=49), and combinations SSRI+SNRI (N=8), SSRI+TCA(N=11) and SNRI+TCA (N=7). We performed a linear regression analysis using the Ordinary Least Squares (OLS) method from the SciPy library (v1.11.1) to measure the association of RWA epochs by medication group adjusting for age, body mass index (BMI), and gender.

Results
Our sample included 48.2% females with a mean age of 52.7 (SD:16.7) and a mean BMI of 32.6 (8.6). The overall mean percentage of RWA epochs was 11.7 (SD:17.5), with a median, 25% and 75% of 4.1, 0.5, and 14.8, respectively. SSRI and SNRI use was associated with a 4.7% and 7.0% increase in RWA (p=&lt; 0.001), respectively, while a 13.6% increase was observed in the SSRI+SNRI group (p= 0.02). Although the TCA and TCA+SSRI groups were associated with only 1.8% and 5.4% increases, they were not significant (p=0.48 and 0.29). The TCA + SNRI group was associated with an increase of 18% (p=&lt; 0.001).

Conclusion
Use of SSRIs and SNRIs alone or in combination, and TCAs combined with SNRI increase the percentage of REM epochs meeting criteria for RWA. Although TCAs alone and combined with SNRIs were not associated with significant increases, this may be due to small sample sizes. These results suggest a potential synergistic effect on RWA criteria in patients using psychotropic medications that necessitates further study. This research has important implications for the diagnostic criteria for RWA and the diagnostic accuracy of RBD.

Support (if any)
We acknowledge the support of NIH grant R21HL170206.
0688 Post-illumination Pupillary Response (PIPR) Is Attenuated in Patients with REM-sleep Behaviour Disorder
Authors: Chan Joey , Chau Steven WH , Huang Bei , Li Tim Man Ho , Chan Ngan Yin , Wing Yun Kwok 
Published: April 2024

Abstract

Introduction
Circadian disruptions are conspicuous in patients with Parkinson’s disease (PD). Previous study showed that melanopsin-mediated post-illumination pupillary response (PIPR) was attenuated in patients with PD. iRBD is often regarded as a prodromal phase of PD, but it remains unclear whether there is an early emergence of changes in PIPR in patients with iRBD.

Methods
This case-control study compared the PIPR, sleep and circadian parameters among controls and patients with iRBD. PIPR was measured by DP-2000 pupillometer (NeurOptics, Irvine, CA, USA). Post-stimulus continuous pupil size recording for 60s was conducted after a 1-second blue stimulus (467nm, 2.0log lux) and a 1-second red light stimulus (632nm, 2.0 log lux), respectively, with 2 minutes of dark adaptation in between. The PIPR was defined as the pupil size at 6s post-stimulus, normalized to the baseline pupil diameter. Net-PIPR is calculated by subtracting PIPR-red from PIPR-blue. One-week actigraphy, sleep diary data and an overnight urinary 6-sulfatoxymelatonin (aMT6s) sample (except those on exogenous melatonin) were also collected. Group difference was compared by Chi Square test or t-test where appropriate. Linear regression analyses were conducted to examine the relationship between PIPR and other circadian parameters.

Results
At present, 50 controls (Age, mean±standard deviation: 62.9±7.1 years) and 37 patients with iRBD (64.4±5.4 years) were recruited. The Net-PIPR was significantly attenuated in the iRBD group (19%±0.11 vs 26%±0.11, p=0.003). Net-PIPR has significant association with aMT6s (B=0.13, 95% Confidence interval (CI)=0.05-0.21, p=0.001), actigraphic M10 (B=2.6, CI:0.8,4.4, p=0.005), mesor (B=1.5, CI: 0.48-2.51, p=0.005), and amplitude (B=1.1, CI:0.2 - 2.1, p=0.02), while controlled for age, gender, photoperiod, time since awake, use of medication. A higher PIPR was associated with a lower odds for iRBD (Odd ratio=0.03, CI:0,89,0.99,p=0.014), adjusted for age, gender, photoperiod, and MOCA score.

Conclusion
Our results showed that PIPR is attenuated in patients with iRBD and is associated with other markers of circadian disruptions. The study supported the early emergence of circadian disruptions in iRBD patients and PIPR is a potential convenient non-invasive circadian marker. Further longitudinal study is needed on whether PIPR would predict circadian disruption and future neurodegeneration.

Support (if any)
Direct grant of The Chinese University of Hong Kong (Ref. 2021.054)
0691 High Prevalence of Periodic Limb Movements of Sleep While Using Hypoglossal Nerve Stimulation Therapy
Authors: Moon Hye-Jin , Lee Chang-Hoon , Cho Unjung , Im KyoungBin 
Published: April 2024

Abstract

Introduction
Periodic limb movements of Sleep (PLMS) often accompany obstructive sleep apnea (OSA) and significantly impact the quality of sleep and treatment adherence. As a novel treatment for OSA, it is crucial to understand the presence and potential impact of PLMS in patients undergoing hypoglossal nerve stimulation (HNS) therapy. Nevertheless, no study to date has investigated PLMS among those in HNS therapy.

Methods
Subjects receiving HNS therapy from December 2020 to August 2023 were consecutively included for this retrospective cohort analysis. PLMS diagnosis was based on periodic limb movement index (PLMI) ≥ 15. Prevalence of PLMS was the main outcome measure and then we compared biometric/ demographic data, comorbidities, medications, data from HNS fine-tune polysomnography (PSG), pre- and post-HNS Epworth Sleepiness Scale (ESS), and baseline OSA parameters between two groups: PLMS versus no PLMS. Statistical analyses were performed using STATA.

Results
One hundred subjects were included for the analysis. The average age was 66.7, with 75% being male, and 82% being non-Hispanic White. Significant PLMS was shown in 52 among 100 subjects receiving HNS treatment. The PLMS group was older (69.0 vs. 64.2 years old, P = 0.008); however, there was no difference observed in terms of sex, race, co-morbidities including depression and anxiety, use of selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitors, dopamine agonists, or alpha-2-delta ligands. The PLMS group had lower pre-HNS ESS score (7.3 vs. 9.4, P = 0.018), and higher baseline non-supine apnea-hypopnea index (AHI) (22.5 vs. 12.9, P = 0.030); however, there were no differences of HNS fine-tune PSG parameters including non-supine AHI (6.6 vs 4.2, P = 0.505), maximum tolerated voltage, HNS usage, and subjective benefit.

Conclusion
The prevalence of PLMS among OSA patients with HNS therapy is notably high at 52%. This high prevalence of PLMS may be attributed to the negative impact of PLMS on CPAP adherence leading to the HNS therapy. Despite the high prevalence of PLMS, PLMS did not result in HNS treatment short-term outcome difference. Further study is needed to investigate the effect of HNS on PLMS and a longer-term impact of PLMS in HNS treatment outcome.

Support (if any)
0696 Slow-wave Sleep and REM Sleep Without Atonia Predict Motor Progression in Parkinson's Disease
Authors: Shen Yun , Tao Mengxing , Li Hanxing , Xie Weiye , Liu Chunfeng 
Published: April 2024

Abstract

Introduction
Growing evidence supports the potential role of sleep in the motor progression of Parkinson's disease (PD). Slow-wave sleep (SWS) and rapid eye movement (REM) sleep without atonia (RWA) are important sleep parameters. The association between SWS and RWA with PD motor progression and their predictive value have not yet been elucidated.

Methods
We retro-prospectively analyzed clinical and polysomnographic data of 136 patients with PD. The motor symptoms were assessed using Unified Parkinson’s Disease Rating Scale Part III (UPDRS III) at baseline and follow-up to determine its progression. Partial correlation analysis was used to explore the cross-sectional associations between slow-wave energy (SWE), RWA and clinical symptoms. Longitudinal analyses were performed using Cox regression and linear mixed-effects models.

Results
Among 136 PD participants, cross-sectional partial correlation analysis showed SWE decreased with the prolongation of the disease course (P = 0.046), RWA density was positively correlated with Hoehn & Yahr (H-Y) stage (tonic RWA, P &lt; 0.001; phasic RWA, P = 0.002). Cox regression analysis confirmed that SWE (HR = 1.739, 95% CI = 1.038-2.914; P = 0.036) and tonic RWA (HR = 0.575, 95% CI = 0.343-0.963; P = 0.032) were predictors of motor symptom progression. Furthermore, we found that lower SWE predicted faster rate of axial motor progression (P &lt; 0.001) while highertonic RWA density was associated with faster rate of rigidity progression (P = 0.006) using linear mixed-effects models.

Conclusion
These findings suggest that SWS and RWA might represent markers of different motor subtypes progression in PD.

Support (if any)
0698 Exploring Age- and Sex-Specific Changes in PLMS in RLS: An Emphasis on Postmenopausal Women
Authors: Mogavero Maria P , DelRosso Lourdes , Lanza Giuseppe , Lanuzza Bartolo , Bruni Oliviero , Strambi Luigi Ferini , Ferri Raffaele 
Published: April 2024

Abstract

Introduction
This study aimed to investigate whether women experiencing restless legs syndrome (RLS) undergo distinct changes in periodic leg movements during sleep (PLMS) during the post-menopausal period, using an age threshold of &gt;50 years as a proxy, in comparison to men of the same age. The assessment of leg movement activity during sleep employed a method that utilized indexes specifically designed for evaluating leg movement periodicity.

Methods
We enrolled a total of 103 participants, 36 of them were aged 18-50 years, comprising 19 men (median age: 40 years) and 17 women (median age: 37 years). Additionally, 67 participants were &gt;50 years old, including 24 men (median age: 66.6 years) and 43 women (median age: 60.0 years). Full night PSG were obtained in all subjects which were scored following standard criteria.

Results
Significant differences were not observed between men in the two age groups. However, in women, a noteworthy and statistically significant increase in the periodicity index was evident in the older group, accompanied by a decrease in isolated leg movements. The intermovement interval graphs revealed a clear age-related enhancement of PLMS in women, particularly in the 16-22 second range, surpassing the changes observed in men. These findings remained consistent when the analysis was replicated by comparing subjects aged 18-45 years with those aged &gt;55 years.

Conclusion
Our results underscore the clinical relevance of evaluating PLMS in postmenopausal women, as these changes are likely associated with the hormonal fluctuations characteristic of this life stage. Translationally, recognizing and addressing PLMS in postmenopausal women is imperative for optimizing their sleep health and mitigating potential health risks associated with sleep disturbances. This study contributes to the broader understanding of RLS and emphasizes the need for targeted interventions in this specific demographic group.

Support (if any)
This study was partially supported by a fund from the Italian Ministry of Health “Ricerca Corrente” (RC n. 2779779) (Drs. Ferri, Lanza, and Lanuzza).
0699 Frequency of Sleep Paralysis as Related to Lifestyle Variables in a Nationwide Student Sample: Preliminary Findings
Authors: Spano Michael , Pace-Schott Edward 
Published: April 2024

Abstract

Introduction
Sleep Paralysis (SP) is a sleep-disturbing experience of muscle atonia while conscious, creating an in-between sensation of wakefulness and dissociation during REM sleep. During SP, one can experience hypnagogic and hypnopompic hallucinations, which may cause feelings of terror and fear. These feelings affect the overall well-being of the experiencers and may impact other aspects of their lives. We investigated factors that may influence the frequency of SP in university students.

Methods
Participants (N=158, 65.19% female, 5.7% non-binary/third gender, 64% white) completed a mixed method, retrospective nationwide survey including items querying demographic variables, lifestyle (i.e., substance use, technology use, social media use), sleeping behaviors (i.e., napping, habitual bedtime, sleep interruption), sleep quality, and frequency of SP.

Results
For questions relating to SP frequency among the 7 categories, most respondents experienced SP “Several” times (36%, N=45, while 14.4% (N=18) experienced SP “Once” and 3.2% (N=4) experienced SP “Daily.” When comparing daily SP experiencers (DSP) to one-time SP experiencers (OSP), 75% (N=3) of DSP napped 4-7 times per week, while half of the OSP (N=9) napped only 1-3 times per month. In our qualitative analysis, many respondents stated they experienced SP most during “napping.” Additionally, the majority of non-SP experiencers (N=18) answered “Never” or “Less than once a month” for napping. For alcohol use, 75% of DSP (N=3) answered “Yes” to “Do you drink alcohol?” while only 55% of OSP (N=10) answered “Yes.” This study could not find differences in caffeine or nicotine use.

Conclusion
Our results suggest that there is a difference in sleeping and lifestyle behaviors between students who experience SP frequently and students who experience SP once or not at all. The most significant difference in the sleeping behaviors is the frequency of napping. The direction of causation between the frequent napping behavior and the SP remains to be determined. Among lifestyle behaviors, SP frequency data suggests that drinking frequency may moderately predict SP. More research is needed regarding whether phone use and/or social media may influence SP frequency, as such behaviors have been shown to influence sleep timing, time duration, and quality.

Support (if any)
None
0700 Identifying Rapid Eye Movement Sleep Behavior Disorder in Veterans Administrative Databases: A Validation Study
Authors: Jones Melissa , Azarian Mehrnaz , Schenck Carlos , Sharafkhaneh Amir , Jorge Ricardo , Razjouyan Javad 
Published: April 2024

Abstract

Introduction
As a first step toward phenotyping large numbers of Veterans with rapid eye movement (REM) sleep behavior disorder (RBD), we investigated the ability of ICD-9 (327.42) and ICD-10 (G47.52) codes to detect Veterans with this clinical diagnosis.

Methods
Subjects were 150 randomly selected Veterans with relevant RBD ICD codes for at least 2 outpatient encounters or 1 inpatient discharge (+RBDcode). Notes from the date of the first ICD diagnosis were reviewed for any documentation of RBD, dream enactment behaviors (DEBs), and targeted pharmacotherapy. The nearest diagnostic, split night, or titration polysomnogram (PSG) report was also reviewed. To calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for probable RBD, a comparison group of 50 Veterans with at least 2 outpatient visits or 1 inpatient discharge summary with ICD-9/ICD-10 codes for OSA and no ICD codes for RBD (-RBDcode) were propensity-matched for age, sex, gender, race, ethnicity, and month-year of first diagnosis.

Results
The final sample consisted of 139 Veterans in +RBDcode (age 64.8±15.2, 94.6% male, 69.8% white, 10% Hispanic) and 47 Veterans in -RBDcode (age 69.6±2.7, 95.8% female, 77.1% white, 4.3% Hispanic) after excluding subjects with unavailable or restricted charts. In +RBDcode, a diagnosis of RBD, overt DEBs, and targeted pharmacotherapy were documented in 130 (93.5%), 103 (74.1%), and 71 (51.1%) of subjects, respectively. No PSGs were documented in 71 (51.5%), reports did not comment on REM sleep without atonia (RSWA) in 29 (20.9%), and REM did not occur in 8 (5.8%) subjects. Only 13 (9.3%) had documented DEBs and a PSG with RSWA. No subjects in -RBDcode had documentation of pRBD. The sensitivity, specificity, PPV, and NPV for pRBD was 100%, 83.9%, 93.5%, and 100%, respectively.

Conclusion
ICD-9 and ICD-10 codes accurately predicted the presence (or absence) of pRBD compared to manual chart review. Next steps are to phenotype Veterans with RBD diagnoses according to comorbidities and outcomes on a nation-wide scale.

Support (if any)
VA CSR&D CDA #IK2CX002363-01A1 [MJ]; NIH-NHLBI-K25 (#1K25HL152006-01) [JR]; seed funding by AHBPCE (#FY2024-002) [JR]; Center for Innovations in Quality, Effectiveness, and Safety (CIN 13-413), Michael E. DeBakey VA Medical Center, Houston, TX.
0702 Periodic Limb Movements in Sleep May Contribute to REM Parasomnia
Authors: Aleem Muhammad Saad , Saqib Fatima , Morris Bryn , Bikov Andras 
Published: April 2024

Abstract

Introduction
Parasomnias are characterised by increased number of arousals. Periodic limb movements in sleep may fragment the sleep; therefore, may trigger parasomnias. However, the association is poorly understood.

Methods
As part of a retrospective service evaluation project, we investigated 131 patients who underwent a full night attended polysomnography due to reported history of parasomnias. Patients were divided into two groups, depending on their periodic limb movements in sleep index (PLMI≥15/h).

Results
Forty-three patients (32%) had PLMS. They more commonly complained about dream enactment (51 vs. 26%, p&lt; 0.01), abnormal movements (59 vs. 39%, p=0.04) and sleep paralysis (11 vs. 1%, p&lt; 0.01) and less likely experienced sleep walking (22 vs. 40%, p=0.04). There was no difference in sleep eating (8 vs. 10%), sexsomnia (0 vs. 2%), nightmares (24 vs. 21%), night terrors (8 vs. 21%), or confusional arousals (17 vs. 30%). Overall, they more likely had a diagnosis of REM parasomnia (71 vs. 50%, p=0.03) and were less likely diagnosed with non-REM parasomnia (45 vs. 70%, p&lt; 0.01). PLMI significantly related to arousal index (ρ=0.37, p&lt; 0.01) and arousal index from NREM (ρ=0.38, p&lt; 0.01); however interestingly, there was no relationship with arousal index from REM (ρ=0.13, p=0.13).

Conclusion
Periodic limb movements in sleep are common in patients with parasomnia and are associated with REM parasomnias. Further studies are necessary to investigate if treatment of PLMS could be beneficial in patients with REM parasomnias.

Support (if any)