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Journal of Neurology Apr 2024Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS), exhibit overlapping early-stage symptoms, complicating definitive diagnosis despite heterogeneous cellular and regional pathophysiology. Additionally, the progression and the eventual conversion of prodromal conditions such as REM behavior disorder (RBD) to PD, MSA, or DLB remain challenging to predict. Extracellular vesicles (EVs) are small, membrane-enclosed structures released by cells, playing a vital role in communicating cell-state-specific messages. Due to their ability to cross the blood-brain barrier into the peripheral circulation, measuring biomarkers in blood-isolated speculative CNS enriched EVs has become a popular diagnostic approach. However, replication and independent validation remain challenging in this field. Here, we aimed to evaluate the diagnostic accuracy of speculative CNS-enriched EVs for parkinsonian disorders.
METHODS
We conducted a PRISMA-guided systematic review and meta-analysis, covering 18 studies with a total of 1695 patients with PD, 253 with MSA, 21 with DLB, 172 with PSP, 152 with CBS, 189 with RBD, and 1288 HCs, employing either hierarchical bivariate models or univariate models based on study size.
RESULTS
Diagnostic accuracy was moderate for differentiating patients with PD from HCs, but revealed high heterogeneity and significant publication bias, suggesting an inflation of the perceived diagnostic effectiveness. The bias observed indicates that studies with non-significant or lower effect sizes were less likely to be published. Although results for differentiating patients with PD from those with MSA or PSP and CBS appeared promising, their validity is limited due to the small number of involved studies coming from the same research group. Despite initial reports, our analyses suggest that using speculative CNS-enriched EV biomarkers may not reliably differentiate patients with MSA from HCs or patients with RBD from HCs, due to their lesser accuracy and substantial variability among the studies, further complicated by substantial publication bias.
CONCLUSION
Our findings underscore the moderate, yet unreliable diagnostic accuracy of biomarkers in speculative CNS-enriched EVs in differentiating parkinsonian disorders, highlighting the presence of substantial heterogeneity and significant publication bias. These observations reinforce the need for larger, more standardized, and unbiased studies to validate the utility of these biomarkers but also call for the development of better biomarkers for parkinsonian disorders.
Topics: Humans; Parkinsonian Disorders; Parkinson Disease; Multiple System Atrophy; Supranuclear Palsy, Progressive; REM Sleep Behavior Disorder; Biomarkers; Extracellular Vesicles; Diagnosis, Differential
PubMed: 38103086
DOI: 10.1007/s00415-023-12093-3 -
Cureus Nov 2023Background and aim Parasomnias are a group of sleep-related movements or emotions like sleepwalking, sleep talking, teeth grinding (Bruxism), nocturnal enuresis (sleep...
Background and aim Parasomnias are a group of sleep-related movements or emotions like sleepwalking, sleep talking, teeth grinding (Bruxism), nocturnal enuresis (sleep enuresis), sleep terrors (night terrors), sleep-related eating disorder (SRED), nightmare disorder, REM Sleep Behavior Disorder (RBD), and confusional arousals. Parasomnias are more common in children than in adults. This study aimed to estimate the prevalence of different parasomnias among university students in Saudi Arabia. Additionally, it aimed to study the relationship between different parasomnias and gender-associated sleep disorders, mental disorders, and other medical diseases, stress, substance use, and medications. Methods This study is a descriptive cross-sectional survey-based study. The target population for this study is university students from different regions of Saudi Arabia. Parasomnia was defined as having at least one of the 11 disorders (over the past six months). Data was collected through an online survey. The survey was distributed on different online platforms to collect data from other regions of Saudi Arabia. The study took place between August and November 2022. Results Among 1,296 participants, 934 (72.1%) were female, and 1,071 (82.6%) were aged 19-24 years. A total of 1054 (81, 3%) participants reported having at least one parasomnia disorder. The most prevalent parasomnias were sleep talking 656 (50.6%), nightmares 650 (50.2%), and confusional arousals 524 (40.4%). The least prevalent parasomnia was sleep-related eating disorder 98 (7.6%). Among participants, 580 (44.8%) had a family history of parasomnia, 439 (33.9%) were diagnosed with sleep disorders, 296 (22.8%) were diagnosed with mental illnesses, and 92 (7.1%) had other medical diseases. Conclusion Parasomnias are prevalent among university students in Saudi Arabia. Parasomnias were higher in female students and in students with a family history of parasomnia. Parasomnias in adults might be a chronic or recurrent disorder. Parasomnias are significantly associated with psychological stress, depression, and anxiety disorders.
PubMed: 38094542
DOI: 10.7759/cureus.48722 -
Seizure Jan 2024In recent years, imaging has emerged as a promising source of several intriguing biomarkers in epilepsy, due to the impressive growth of imaging technology, supported by... (Review)
Review
In recent years, imaging has emerged as a promising source of several intriguing biomarkers in epilepsy, due to the impressive growth of imaging technology, supported by methodological advances and integrations of post-processing techniques. Bearing in mind the mutually influencing connection between sleep and epilepsy, we focused on sleep-related hypermotor epilepsy (SHE) and sudden unexpected death in epilepsy (SUDEP), aiming to make order and clarify possible clinical utility of emerging multimodal imaging biomarkers of these two epilepsy-related entities commonly occurring during sleep. Regarding SHE, advanced structural techniques might soon emerge as a promising source of diagnostic and predictive biomarkers, tailoring a targeted therapeutic (surgical) approach for MRI-negative subjects. Functional and metabolic imaging may instead unveil SHE's extensive and night-related altered brain networks, providing insights into distinctions and similarities with non-epileptic sleep phenomena, such as parasomnias. SUDEP is considered a storm that strikes without warning signals, but objective subtle structural and functional alterations in autonomic, cardiorespiratory, and arousal centers are present in patients eventually experiencing SUDEP. These alterations could be seen both as susceptibility and diagnostic biomarkers of the underlying pathological ongoing loop ultimately ending in death. Finally, given that SHE and SUDEP are rare phenomena, most evidence on the topic is derived from small single-center experiences with scarcely comparable results, hampering the possibility of performing any meta-analytic approach. Multicenter, longitudinal, well-designed studies are strongly encouraged.
Topics: Humans; Sudden Unexpected Death in Epilepsy; Death, Sudden; Epilepsy, Reflex; Sleep; Biomarkers; Multicenter Studies as Topic
PubMed: 38088013
DOI: 10.1016/j.seizure.2023.12.001 -
MedRxiv : the Preprint Server For... Nov 2023Damaging coding variants in are a genetic risk factor for rapid eye movement sleep behavior disorder (RBD), which is a known early feature of synucleinopathies....
BACKGROUND
Damaging coding variants in are a genetic risk factor for rapid eye movement sleep behavior disorder (RBD), which is a known early feature of synucleinopathies. Recently, a population-specific non-coding variant (rs3115534) was found to be associated with PD risk and earlier disease onset in individuals of African ancestry.
OBJECTIVES
To investigate whether the rs3115534 PD risk variant is associated with RBD.
METHODS
We studied 709 persons with PD and 776 neurologically healthy controls from Nigeria. The rs3115534 risk variant status was imputed from previous genotyping for all. Symptoms of RBD were assessed with the RBD screening questionnaire (RBDSQ).
RESULTS
The non-coding rs3115534 risk variant is associated with possible RBD in individuals of Nigerian origin (Beta = 0.3640, SE = 0.103, P =4.093e-04), as well as after adjusting for PD status (Beta = 0.2542, SE = 0.108, P = 0.019) suggesting that this variant may have the same downstream consequences as coding variants.
CONCLUSIONS
We show that the non-coding rs3115534 risk variant is associated with increased RBD symptomatology in Nigerians with PD. Further research is required to assess association with polysomnography-defined RBD.
PubMed: 38076854
DOI: 10.1101/2023.11.07.23298092 -
Frontiers in Neurology 2023Differentiating between non-rapid eye movement (NREM) parasomnias and sleep-related hypermotor epilepsy (SHE) is challenging, as they exhibit similar episodes during...
Differentiating between non-rapid eye movement (NREM) parasomnias and sleep-related hypermotor epilepsy (SHE) is challenging, as they exhibit similar episodes during sleep. A relatively high prevalence of NREM parasomnias has been detected in families with SHE. However, the common pathophysiologic mechanism is not completely clear. There have been no previous reports of -related SHE combined with NREM parasomnias. In this report, we describe a 17 years-old male patient from a mutation family who exhibited complex abnormal behaviors during sleep, which have been confirmed as epileptic seizures combined with NREM parasomnias through video-electroencephalogram (vEEG) and video-polysomnography (vPSG). The present article provides a reasoning process to evaluate unusual nocturnal behaviors. Furthermore, our analysis suggests a new potential association between NREM parasomnias and mutations.
PubMed: 38073640
DOI: 10.3389/fneur.2023.1280348 -
JAMA Neurology Jan 2024Nonmotor symptoms of Parkinson disease (PD) often predate the movement disorder by decades. Currently, there is no blood biomarker to define this prodromal phase.
IMPORTANCE
Nonmotor symptoms of Parkinson disease (PD) often predate the movement disorder by decades. Currently, there is no blood biomarker to define this prodromal phase.
OBJECTIVE
To investigate whether α-synuclein in neuronally derived serum-extracellular vesicles identifies individuals at risk of developing PD and related dementia.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective, cross-sectional multicenter study of serum samples included the Oxford Discovery, Marburg, Cologne, and Parkinson's Progression Markers Initiative cohorts. Participants were recruited from July 2013 through August 2023 and samples were analyzed from April 2022 through September 2023. The derivation group (n = 170) included participants with isolated rapid eye movement sleep behavior disorder (iRBD) and controls. Two validation groups were used: the first (n = 122) included participants with iRBD and controls and the second (n = 263) included nonmanifest GBA1N409S gene carriers, participants with iRBD or hyposmia, and available dopamine transporter single-photon emission computed tomography, healthy controls, and patients with sporadic PD. Overall the study included 199 participants with iRBD, 20 hyposmic participants with available dopamine transporter single-photon emission computed tomography, 146 nonmanifest GBA1N409S gene carriers, 21 GBA1N409S gene carrier patients with PD, 50 patients with sporadic PD, and 140 healthy controls. In the derivation group and validation group 1, participants with polysomnographically confirmed iRBD were included. In the validation group 2, at-risk participants with available Movement Disorder Society prodromal markers and serum samples were included. Among 580 potential participants, 4 were excluded due to alternative diagnoses.
EXPOSURES
Clinical assessments, imaging, and serum collection.
MAIN OUTCOME AND MEASURES
L1CAM-positive extracellular vesicles (L1EV) were immunocaptured from serum. α-Synuclein and syntenin-1 were measured by electrochemiluminescence. Area under the receiver operating characteristic (ROC) curve (AUC) with 95% CIs evaluated biomarker performance. Probable prodromal PD was determined using the updated Movement Disorder Society research criteria. Multiple linear regression models assessed the association between L1EV α-synuclein and prodromal markers.
RESULTS
Among 576 participants included, the mean (SD) age was 64.30 (8.27) years, 394 were male (68.4%), and 182 were female (31.6%). A derived threshold of serum L1EV α-synuclein distinguished participants with iRBD from controls (AUC = 0.91; 95% CI, 0.86-0.96) and those with more than 80% probability of having prodromal PD from participants with less than 5% probability (AUC = 0.80; 95% CI, 0.71-0.89). Subgroup analyses revealed that specific combinations of prodromal markers were associated with increased L1EV α-synuclein levels. Across all cohorts, L1EV α-synuclein differentiated participants with more than 80% probability of having prodromal PD from current and historic healthy control populations (AUC = 0.90; 95% CI, 0.87-0.93), irrespective of initial diagnosis. L1EV α-synuclein was increased in at-risk participants with a positive cerebrospinal fluid seed amplification assay and was above the identified threshold in 80% of cases (n = 40) that phenoconverted to PD or related dementia.
CONCLUSIONS AND RELEVANCE
L1EV α-synuclein in combination with prodromal markers should be considered in the stratification of those at high risk of developing PD and related Lewy body diseases.
Topics: Female; Humans; Male; Middle Aged; alpha-Synuclein; Biomarkers; Cross-Sectional Studies; Dopamine Plasma Membrane Transport Proteins; Extracellular Vesicles; Lewy Body Disease; Parkinson Disease; REM Sleep Behavior Disorder; Retrospective Studies
PubMed: 38048087
DOI: 10.1001/jamaneurol.2023.4398 -
Renal Failure 2023This study evaluated the efficacy and safety of limb ischemic preconditioning (LIPC) in treating restless leg syndrome (RLS) in maintenance hemodialysis (MHD) patients. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study evaluated the efficacy and safety of limb ischemic preconditioning (LIPC) in treating restless leg syndrome (RLS) in maintenance hemodialysis (MHD) patients.
METHODS
A total number of 45 patients participated in the study. They were randomly divided into LIPC group and control group. The LIPC was performed by inflating the limb ischemic preconditioning training device in the patient's thigh to 200 mmHg to create transient ischemia, whereas control group inflated the device to 20 mmHg. International Restless Legs Syndrome (IRLS), Clinical Global Impression Scale (CGI-S), and Medical Outputs Study Sleep Scale were employed to evaluate LIPC effectiveness. The primary endpoint was the 'rate of clinical improvement in RLS severity', defined as the percentage of patients who had an IRLS score decrease of ≥5 points in each group.
RESULTS
After intervention, the rate of clinical improvement in RLS severity was 56.5% in the LIPC group and 13.6% in the control group (13 (56.5) 3 (13.6), = 0.003). In addition, the LIPC group's IRLS, CGI-S scores, the sleep disturbance and somnolence scores showed a significant downward trend compared to the control group (-5.5 ± 5.3 - 1.0 ± 3.8, = 0.002; -1.7 ± 1.2 - 0.5 ± 1.4, = 0.003; -15.5 ± 17.8 3.7 ± 12.0, < 0.001; -9.9 ± 18.8 - 2.4 ± 8.6, = 0.003). During the study, there were no serious adverse event in any of the patients.
CONCLUSIONS
LIPC could be employed to effectively and safely alleviate the RLS symptoms in MHD patients.
Topics: Humans; Restless Legs Syndrome; Double-Blind Method; Renal Dialysis; Ischemic Preconditioning; Sleep Wake Disorders; Treatment Outcome; Severity of Illness Index
PubMed: 38047534
DOI: 10.1080/0886022X.2023.2283589 -
Journal of Medical Case Reports Nov 2023Sleep-related painful erections are characterized by deep penile pain that occurs during erections in the rapid eye movement stage of sleep.
BACKGROUND
Sleep-related painful erections are characterized by deep penile pain that occurs during erections in the rapid eye movement stage of sleep.
CASE PRESENTATION
This case presents a 43-year-old Chinese Han patient with sleep-related painful erections. Turgid painful erections (4-5 episodes of tumescence) during the sleep hours caused pain. Further, blood testing revealed an abnormal increase in white blood cells (123 × 10/L). The patient was diagnosed with chronic myeloid leukemia by bone marrow biopsy, BCR::ABL1 fusion gene testing, and Philadelphia chromosome. However, the sleep-related painful erections have dramatically decreased in frequency of erectile pain after chemotherapy for Chronic myeloid leukemia in our case.
CONCLUSION
We considered that the occurrence of sleep-related painful erections was related to chronic myeloid leukemia and the case might be secondary sleep-related painful erections.
Topics: Male; Humans; Adult; Sleep; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Sleep, REM; Chronic Disease; REM Sleep Parasomnias; Pain
PubMed: 38031195
DOI: 10.1186/s13256-023-04222-3 -
Frontiers in Pharmacology 2023While zolpidem is considered as an example of a gender effect on drug response, there is insufficient evidence to reach a consensus. This study aimed to investigate...
While zolpidem is considered as an example of a gender effect on drug response, there is insufficient evidence to reach a consensus. This study aimed to investigate gender differences in adverse events (AEs) of zolpidem. We estimated the difference between the reporting odds ratios (RORs) calculated in gender subgroups for the AEs signals detected in data mining using 2015-2019 Korea voluntary adverse drug events reporting system (KAERS) data. Different reporting risk by gender was evaluated by using the log RORs being significantly different by gender at the 5% significance level and the 95% confidence intervals of the gender ROR. A total of 94 AE signals were detected. Among these, 35 signals showed significant disparities by gender at the 5% level or were detected only in one gender. When categorized by similarity of AEs, parasomnia including somnambulism and paroniria, and cardiovascular disorders including coronary thrombosis had higher reporting risks in women. Men were more likely to report cognitive disorders such as delirium, insomnia related disorders, and movement disorders. Among all AEs with gender differences in reporting risk, the difference in somnambulism was the most consistent and substantial. For several AEs associated with zolpidem, gender-based reporting disparities were evident. Notably, women exhibited a higher susbeptibility to somnambulism, potentially serious adverse effects of zolpidem. This underscores the need for further investigation into the underlying factors influencing these gender-specific reporting patterns.
PubMed: 38026947
DOI: 10.3389/fphar.2023.1256245 -
Cureus Nov 2023Major depressive disorder (MDD) is associated with both insomnia and hypersomnia, but it predominantly decreases sleep continuity and leads to a decrease in rapid eye...
Major depressive disorder (MDD) is associated with both insomnia and hypersomnia, but it predominantly decreases sleep continuity and leads to a decrease in rapid eye movement (REM) latency, an increase in REM sleep duration, and an increase in REM density. Some of these changes persist even when MDD is treated and can be associated with a recurrence of MDD. Antidepressants can potentially complicate the relationship between REM sleep and depression, as a majority of patients report improved sleep when prescribed selective serotonin reuptake inhibitors (SSRIs) but some case reports mention that SSRIs have been associated with REM inhibition, resulting in decreased REM sleep. We present a case report of a young patient with MDD who started experiencing multiple episodes of distressing sleep paralysis after he started taking sertraline and resolved as he was tapered off the medication. Through references from the literature indicating a potential link between parasomnias and SSRIs, we were able to discuss that SSRIs can potentially lead to isolated sleep paralysis and should be considered as an uncommon yet distressing side effect although not listed in the package insert. Isolated sleep paralysis has been defined in the literature as the inability to perform voluntary movements of the trunk and all limbs for a period of seconds to minutes at the beginning of sleep or upon waking up. Further research is needed to clarify the impact of SSRIs on sleep and practice guidelines should be clarified in regard to their role.
PubMed: 38024073
DOI: 10.7759/cureus.49014