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Pediatric Neurology Oct 2023Allan-Herndon-Dudley syndrome (AHDS) is caused by mutations in the SLC16A2 gene, encoding for the monocarboxylate transporter 8 (MCT8). Central hypothyroidism and...
Allan-Herndon-Dudley syndrome (AHDS) is caused by mutations in the SLC16A2 gene, encoding for the monocarboxylate transporter 8 (MCT8). Central hypothyroidism and chronic peripheral thyrotoxicosis result in a severe phenotype, mainly characterized by poor growth, intellectual disability, spastic tetraparesis, and movement disorders, including paroxysmal ones (startle reaction and paroxysmal dyskinesias). Seizures are rarely reported. We conducted a retrospective analysis on video electroencephalography (EEG) recordings in four subjects with AHDS, focused on paroxysmal events. Among other manifestations recorded on EEG, we diagnosed repetitive sleep starts (RSS) in all subjects. RSS are a paroxysmal nonepileptic phenomenon occurring during sleep, similar to epileptic spasms in their clinical and electromyography characteristics, but not related to any EEG change. This is the first report on RSS in AHDS. We present video-EEG polygraphic documentation, suggesting that RSS could be underestimated or misdiagnosed. The importance of a correct diagnosis is crucial in a therapeutic perspective.
Topics: Humans; Retrospective Studies; Sleep-Wake Transition Disorders; Mental Retardation, X-Linked; Mutation; Muscle Hypotonia; Muscular Atrophy; Monocarboxylic Acid Transporters; Symporters
PubMed: 37542971
DOI: 10.1016/j.pediatrneurol.2023.06.012 -
Journal of Clinical Medicine Jul 2023A high prevalence of sleep disturbances has been reported in children with neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD), attention deficit...
A high prevalence of sleep disturbances has been reported in children with neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intellectual disability (ID). The etiology of sleep disorders in these children is heterogeneous and, recently, iron deficiency has received increasing attention. This study aims to investigate sleep features in children with NDDs and to explore a possible correlation between serum iron status biomarkers and qualitative features of sleep. We included 4- to 12-year-old children with a diagnosis of ASD, ADHD, or ID and assessed their sleep features through the children's sleep habits questionnaire (CSHQ). Venous blood samples were collected to investigate ferritin, transferrin, and iron levels. The mean CSHQ total score exceeds the cut-off in all groups of children. In the ASD group, the Parasomnias subscale negatively correlated with serum ferritin levels (Rho = 0.354; = 0.029). Our findings may suggest the existence of an association between iron status, sleep quality, and neurodevelopmental processes. In clinical practice, sleep assessment should be included in the routine assessment for patients with NDDs. Furthermore, a routine assessment of iron status biomarkers should be recommended for children with NDDs who have sleep disturbances.
PubMed: 37568350
DOI: 10.3390/jcm12154949 -
Mayo Clinic Proceedings Oct 2023To examine the association between parasomnias, including rapid eye movement sleep behavior disorder (RBD) and sleep walking (SW), and mortality risk in a large-scale...
OBJECTIVE
To examine the association between parasomnias, including rapid eye movement sleep behavior disorder (RBD) and sleep walking (SW), and mortality risk in a large-scale population-based cohort.
METHODS
This prospective cohort study was based on 25,695 participants from the Health Professionals Follow-up Study, a population-based cohort of male health professionals in the United States. Probable SW (pSW) and probable RBD (pRBD) were measured by questions adapted from the Mayo Sleep Questionnaire in 2012. All-cause mortality and cause-specific mortality were ascertained through the national registry, reports by the families, and the postal system from January 1, 2012, through June 30, 2018.
RESULTS
Of the studied population, 223 reported pSW and 2720 reported pRBD. During 6 years of follow-up (2012 to 2018), 4743 mortality cases were documented. The co-occurrence of both probable parasomnias was associated with higher all-cause mortality risk (P=.008), and the adjusted hazard ratio (HR) of mortality was 1.65 (95% CI, 1.20 to 2.28) compared with participants without either probable parasomnia after adjustment for major lifestyle, sleep, and metabolic risk factors, and chronic diseases. Significant associations were found for mortality attributed to neurodegenerative diseases (adjusted HR for both parasomnias vs none, 4.57; 95% CI, 2.62 to 7.97) and accidents (adjusted HR for both parasomnias vs none, 7.36; 95% CI, 2.95 to 18.4). Having pSW alone was associated with all-cause mortality, and pSW and pRBD were individually associated with mortality attributed to neurodegenerative diseases and accidents too (P<.05 for all).
CONCLUSION
Probable parasomnia was associated with a higher risk of all-cause mortality and mortality attributed to neurodegenerative diseases and accidents.
Topics: Humans; Male; Prospective Studies; Follow-Up Studies; Parasomnias; REM Sleep Behavior Disorder; Neurodegenerative Diseases; Surveys and Questionnaires
PubMed: 37793724
DOI: 10.1016/j.mayocp.2023.06.018 -
Sleep Medicine Sep 2023Brain iron status is fundamental in RLS pathogenesis. The aim of this study was to determine the clinical efficacy and brain iron concentration improvement in RLS... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Brain iron status is fundamental in RLS pathogenesis. The aim of this study was to determine the clinical efficacy and brain iron concentration improvement in RLS patients with IDA, using 1500 mg FCM.
METHODS
This is a randomized, double-blinded, placebo-controlled study. RLS patients with IDA were grouped into either 1500 mg FCM or placebo. The primary outcomes were the change from baseline on the International Restless Legs Syndrome Study Group scale (IRLS) and brain iron measured by QSM and R2∗.
RESULTS
A total of 18 RLS patients with IDA were enrolled, 10 in the FCM group and 8 in the placebo. At the week 6 endpoint, the FCM group showed significant improvement in both IRLS (-13.60 ± 9.47 vs. -3.63 ± 5.40, p = 0.011) and VAS (-40.50 ± 28.81 vs. -0.63 ± 28.28, p = 0.004) from baseline. Change from baseline with R2∗ techniques showed a treatment effect for the thalamus and QSM technique for both the substantia nigra and pulvinar. A correlation was proved between the IRLS difference and the difference of QSM in thalamus (p = 0.028).
CONCLUSION
This study demonstrates that 1500 mg FCM effectively treats RLS symptoms in IDA patients over six weeks, with MRI measurements of improved brain iron content serving as a potential biomarker for RLS patients.
Topics: Humans; Iron; Anemia, Iron-Deficiency; Restless Legs Syndrome; Ferric Compounds; Brain; Treatment Outcome
PubMed: 37437492
DOI: 10.1016/j.sleep.2023.06.023 -
Sleep Feb 2024Dual orexin receptor antagonists (DORAs) are emerging treatments for insomnia. This meta-analysis study aimed to assess the safety of FDA-approved DORAs (suvorexant,... (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVES
Dual orexin receptor antagonists (DORAs) are emerging treatments for insomnia. This meta-analysis study aimed to assess the safety of FDA-approved DORAs (suvorexant, lemborexant, and daridorexant), focusing on narcolepsy-like symptoms associated with these drugs.
METHODS
Five prominent databases were searched to identify randomized controlled trials (RCTs) on this topic. Primary safety outcomes included treatment-emergent adverse events (TEAEs), treatment-related TEAEs, TEAEs leading to discontinuation, and serious TEAEs. Excessive daytime sleepiness (EDS), sleep paralysis, and hallucinations were categorized as adverse events (AEs)-related narcolepsy-like symptoms.
RESULTS
Eleven RCTs with 7703 patients were included. DORAs were associated with a higher risk of TEAEs (risk ratio [RR], 1.09; 95% confidence interval [CI], 1.03 to 1.15) and treatment-related TEAEs (RR, 1.69; 95% CI: 1.49 to 1.92) when compared to placebo. The DORA group exhibited a significantly higher risk of EDS (RR, 2.15; 95% CI: 1.02 to 4.52) and sleep paralysis (RR, 3.40; 95% CI: 1.18 to 9.80) compared to the placebo group.
CONCLUSION
This meta-analysis achieved a comparative evaluation of the clinical safety and tolerability of FDA-approved DORAs for primary insomnia, specifically focusing on AEs-related narcolepsy-like symptoms. This study contributes to understanding the safety profile of FDA-approved DORAs for treating insomnia.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Orexin Receptor Antagonists; Sleep Paralysis; Narcolepsy
PubMed: 37950346
DOI: 10.1093/sleep/zsad293 -
European Journal of Neurology Jun 2024This study compared the features of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) and antidepressant-related REM sleep behaviour disorder (RBD) with... (Observational Study)
Observational Study
BACKGROUND AND PURPOSE
This study compared the features of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) and antidepressant-related REM sleep behaviour disorder (RBD) with the aim of highlighting markers that might distinguish the two entities.
METHODS
The observational cohort study included RBD patients with and without antidepressant use (antiD+ and antiD- patients, respectively), without cognitive impairment and parkinsonism. Clinical features of RBD, subtle motor and non-motor symptoms of parkinsonism, sleep architecture, REM atonia index, dopamine transporter-single photon emission computed tomography (DAT-SPECT) and skin biopsies for the intraneuronal alpha-synuclein (α-syn), were evaluated in the baseline work-up.
RESULTS
Thirty-nine patients, 10 antiD+ and 29 antiD-, were included. AntiD+ patients (more frequently female) reported more psychiatric symptoms, less violent dream enactment, and less frequent hyposmia. Dermal α-syn was detected in 93.1% of antiD- versus 30% of antiD+ patients (p = 0.00024). No differences appeared in other motor and non-motor symptoms, Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III score, DAT-SPECT, or polysomnographic features.
CONCLUSIONS
Patients with antidepressant-related RBD have clinical and neuropathological features suggesting a lower risk of evolution than those with iRBD.
Topics: Humans; REM Sleep Behavior Disorder; Female; Male; Aged; Middle Aged; Antidepressive Agents; Biomarkers; Tomography, Emission-Computed, Single-Photon; alpha-Synuclein; Cohort Studies; Dopamine Plasma Membrane Transport Proteins
PubMed: 38409939
DOI: 10.1111/ene.16260 -
Sleep Medicine Oct 2023Neurodegenerative diseases often alter sleep architecture, complicating the application of the standard sleep scoring rules. There are no recommendations to overcome...
BACKGROUND
Neurodegenerative diseases often alter sleep architecture, complicating the application of the standard sleep scoring rules. There are no recommendations to overcome this problem. Our aim was to develop a scoring method that incorporates the stages previously applied in dementia with Lewy Bodies (DLB), anti-IgLON5 disease, and fatal insomnia, and to test it in patients with alpha-synucleinopathies.
METHODS
Video-polysomnographies (VPSG) of nine patients (DLB:3, Parkinson's disease (PD):3, and multiple system atrophy (MSA):3) selected for their difficulty in applying standard rules were scored independently by two authors, using additional Sleep/Wake stages. These included Abnormal Wake, Subwake, Undifferentiated NREM sleep (UNREM), Poorly structured N2 (P-S N2) and abnormal REM sleep including REM without atonia (RWA), REM without low-amplitude, mixed-frequency EEG activity (RWL) and REM without rapid eye movements (RWR).
RESULTS
Patients (4 females) had a median age of 74 (range 63-85). Six patients (all with PD or DLB) had abnormal EEG awake and Subwake stage. UNREM sleep was present in all patients, typically at sleep onset, and was the most common sleep stage in five. P-S N2 was recorded only in the three patients with MSA. Periods of normal and abnormal NREM coexisted in three patients. RWA was the predominant REM subtype, RWR occurred mainly in patients with MSA and RWL in those with DLB. Six patients had brief REM episodes into NREM sleep which we termed "Encapsulated RBD".
CONCLUSION
Our scoring system allows an accurate description of the complex sleep-wake changes in patients with alpha-synucleinopathies.
Topics: Female; Humans; Synucleinopathies; Pilot Projects; Sleep; Parkinson Disease; Multiple System Atrophy; Parasomnias; Muscle Hypotonia
PubMed: 37678074
DOI: 10.1016/j.sleep.2023.08.022 -
Journal of Neurology Apr 2024Anti-IgLON5 disease is a rare but potentially reversible cause of cognitive impairment, sleep disturbances, dysautonomia, and movement disorders. It is an autoimmune... (Review)
Review
BACKGROUND
Anti-IgLON5 disease is a rare but potentially reversible cause of cognitive impairment, sleep disturbances, dysautonomia, and movement disorders. It is an autoimmune encephalitis which, due to its insidious onset, could mimic neurodegenerative disorders, and multiple symptoms overlap with those seen in dementia with Lewy bodies (DLB). We hypothesized that the symptomatology and findings in patients with anti-IgLON5 disease overlapped with that of DLB.
OBJECTIVES
To assess the commonality of features in anti-IgLON5 disease and DLB and identify potential red flags for anti-IgLON5 disease in patients undergoing diagnostic evaluation for DLB.
METHODS
We searched in MEDLINE, Web of Science, and Embase from inception on December the 8th, 2022 with the search term "IgLON5". We performed a systematic review of case reports and case series of anti-IgLON5 disease, and two reviewers independently extracted data on symptoms and findings. Frequencies of symptoms were compared with consensus criteria for DLB.
RESULTS
We included 57 studies with 127 individual case reports of anti-IgLON5 disease (mean age 63 years at diagnosis, median symptom duration 2 years). Cognitive dysfunction was reported in 45% of cases, REM-sleep behavioral disorder in 15%, and 14% had parkinsonism. Respiratory insufficiency was reported in 37%, and bulbar symptoms in 67%.
CONCLUSIONS
We found a significant overlap between anti-IgLON5 disease and DLB. We propose that anti-IgLON5 disease should be considered in young patients with DLB with chorea, gaze palsy, early dysphagia, or prominent respiratory symptoms. Our study contributes to the emerging knowledge on symptoms and biomarkers in anti-IgLON5 disease.
Topics: Humans; Middle Aged; Lewy Body Disease; Cognitive Dysfunction; Sleep Apnea, Obstructive; REM Sleep Behavior Disorder; Sleep Wake Disorders; Encephalitis; Hashimoto Disease
PubMed: 38195895
DOI: 10.1007/s00415-023-12145-8 -
Sleep Medicine Clinics Mar 2024Exploding head syndrome (EHS) has historically been viewed as a disorder predominantly affecting older people and being more common in females. Through a comprehensive... (Review)
Review
Exploding head syndrome (EHS) has historically been viewed as a disorder predominantly affecting older people and being more common in females. Through a comprehensive review of data since 2005, this scoping review provides updated evidence from 4082 participants reporting EHS across a variety of study designs on: how EHS presents; key information on comorbidity and correlates of EHS; how EHS is experienced in terms of symptoms and beliefs; causal theories arising from the research reviewed; and evidence-based information on how research has reported on the management of EHS. Since 2005, EHS has attracted increasing research interest; however, there are significant gaps in the research that are hindering a better understanding of EHS that might be helpful for clinicians.
Topics: Humans; Parasomnias
PubMed: 38368060
DOI: 10.1016/j.jsmc.2023.10.007