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Frontiers in Neurology 2023No interventional study has been conducted in China to assess efficacy and safety of perampanel in treating Chinese patients with epilepsy, nor has there been any study...
BACKGROUND
No interventional study has been conducted in China to assess efficacy and safety of perampanel in treating Chinese patients with epilepsy, nor has there been any study on perampanel early add-on therapy in China. This interventional study aimed to assess efficacy and safety of perampanel as an early add-on treatment of focal-onset seizures (FOS) with or without focal-to-bilateral tonic-clonic seizures (FBTCS) in Chinese patients.
METHODS
In this multicenter, open-label, single-arm, phase 4 interventional study, Chinese patients ≥ 12 years old with FOS with or without FBTCS who failed anti-seizure medication (ASM) monotherapy from 15 hospitals in China were enrolled and treated with perampanel add-on therapy (8-week titration followed by 24-week maintenance). The primary endpoint was 50% responder rate. Secondary endpoints included seizure-freedom rate and changes in seizure frequency from baseline. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were recorded.
RESULTS
The full analysis set included 150 patients. The mean maintenance perampanel dose was 5.9 ± 1.5 mg/day and the 8-month retention rate was 72%. The 50% responder rate and seizure-freedom rate for all patients during maintenance were 67.9 and 30.5%, respectively. Patients with FBTCS had higher 50% responder rate (96.0%) and seizure-freedom rate (76.0%) during maintenance. Patients on concomitant sodium valproate had a significantly higher seizure-freedom rate than those on concomitant oxcarbazepine. Eight-six (55.1%) patients experienced treatment-related TEAEs, and the most common TEAEs were dizziness (36.5%), hypersomnia (11.5%), headache (3.9%), somnolence (3.2%), and irritability (3.2%). Withdrawal due to TEAEs occurred to 14.7% of the patients.
CONCLUSION
Perampanel early add-on was effective and safe in treating Chinese patients≥12 years old with FOS with or without FBTCS.www.chictr.org.cn, Identifier ChiCTR2000039510.
PubMed: 37712083
DOI: 10.3389/fneur.2023.1236046 -
The Journal of Clinical Pediatric... Jul 2023Orofacial myofunctional disorders (OMD) and sleep-disordered breathing (SDB) may present as comorbidities. Orofacial characteristics might serve as a clinical marker of...
Orofacial myofunctional disorders (OMD) and sleep-disordered breathing (SDB) may present as comorbidities. Orofacial characteristics might serve as a clinical marker of SDB, allowing early identification and management of OMD and improving treatment outcomes for sleep disorders. The study aims to characterize OMD in children with SDB symptoms and to investigate possible relationships between the presence of various components of OMD and symptoms of SDB. A cross-sectional study of healthy children aged 6-8 from primary schools was conducted in central Vietnam in 2019. SDB symptoms were collected using the parental Pediatric Sleep Questionnaire, Snoring Severity Scale, Epworth Daytime Sleepiness Scale, and lip-taping nasal breathing assessment. Orofacial myofunctional evaluation included assessment of tongue mobility, as well as of lip and tongue strength using the Iowa Oral Performance Instrument, and of orofacial characteristics by the protocol of Orofacial Myofunctional Evaluation with Scores. Statistical analysis was used to investigate the relationship between OMD components and SDB symptoms. 487 healthy children were evaluated, of whom 46.2% were female. There were 7.6% of children at high risk of SDB. Children with habitual snoring (10.3%) had an increased incidence of restricted tongue mobility and decreased lip and tongue strength. Abnormal breathing patterns (22.4%) demonstrated lower posterior tongue mobility and lower muscle strength. Daytime sleepiness symptoms were associated with changes in muscle strength, facial appearance, and impaired orofacial function. Lower strengths of lip and tongue or improper nasal breathing were more likely to be present in children with reported sleep apnea (6.6%). Neurobehavioral symptoms of inattention and hyperactivity were linked to anomalous appearance/posture, increases in tongue mobility and oral strength. This study demonstrates a prevalence of orofacial myofunctional anomalies in children exhibiting SDB symptoms. Children with prominent SDB symptoms should be considered as candidates for further orofacial myofunctional assessment.
Topics: Humans; Child; Female; Male; Snoring; Cross-Sectional Studies; Sleep Apnea Syndromes; Disorders of Excessive Somnolence; Surveys and Questionnaires
PubMed: 37408343
DOI: 10.22514/jocpd.2023.032 -
Chest Mar 2024In people with OSA, excessive daytime sleepiness is a prominent symptom and can persist despite adherence to CPAP, the first-line therapy for OSA. Pitolisant was...
BACKGROUND
In people with OSA, excessive daytime sleepiness is a prominent symptom and can persist despite adherence to CPAP, the first-line therapy for OSA. Pitolisant was effective in reducing daytime sleepiness in two 12-week randomized controlled trials (RCTs), one in patients adherent to CPAP (BF2.649 in Patients With OSA and Treated by CPAP But Still Complaining of EDS [HAROSA 1]) and the other in patients refusing or not tolerating CPAP (BF2.649 in Patients With OSA, Still Complaining of EDS and Refusing to be Treated by CPAP [HAROSA 2]).
RESEARCH QUESTION
Does the efficacy and safety of pitolisant persist when these patients take it long-term?
STUDY DESIGN AND METHODS
All adults included in the HAROSA 1 and HAROSA 2 RCTs (both pitolisant and placebo arms) were offered pitolisant (up to 20 mg/d) after completion of the short-term double-anonymized phase (ie, from week 13) in an open-label cohort study. The primary efficacy outcome was the change in Epworth Sleepiness Scale score between baseline and week 52. Safety outcomes were treatment-emergent adverse event(s) (TEAE[s]), serious TEAEs, and special interest TEAEs.
RESULTS
Out of 512 adults included in the two RCTs, 376 completed the 1-year follow-up. The pooled mean difference in Epworth Sleepiness Scale score from baseline to 1 year for the intention-to-treat sample was -8.0 (95% CI, -8.3 to -7.5). The overall proportions of TEAEs, serious TEAEs, and TEAEs of special interest were 35.1%, 2.0%, and 11.1%, respectively, without any significant difference between patients in the initial pitolisant and placebo arms. No cardiovascular safety issues were reported.
INTERPRETATION
Pitolisant is effective in reducing daytime sleepiness over 1 year in adults with OSA, with or without CPAP treatment. Taken for 1 year, it has a good safety profile (including cardiovascular).
TRIAL REGISTRATION
ClinicalTrials.gov; Nos.: NCT01071876 and NCT01072968; URL: www.
CLINICALTRIALS
gov.
Topics: Adult; Humans; Sleepiness; Piperidines; Disorders of Excessive Somnolence; Continuous Positive Airway Pressure; Sleep Apnea, Obstructive; Treatment Outcome
PubMed: 37979718
DOI: 10.1016/j.chest.2023.11.017 -
BMC Anesthesiology Jul 2023The severity of sleep-disordered breathing is known to worsen postoperatively and is associated with increased cardio-pulmonary complications and increased resource... (Randomized Controlled Trial)
Randomized Controlled Trial
The impact of semi-upright position on severity of sleep disordered breathing in patients with obstructive sleep apnea: a two-arm, prospective, randomized controlled trial.
BACKGROUND
The severity of sleep-disordered breathing is known to worsen postoperatively and is associated with increased cardio-pulmonary complications and increased resource implications. In the general population, the semi-upright position has been used in the management of OSA. We hypothesized that the use of a semi-upright position versus a non-elevated position will reduce postoperative worsening of OSA in patients undergoing non-cardiac surgeries.
METHODS
This study was conducted as a prospective randomized controlled trial of perioperative patients, undergoing elective non-cardiac inpatient surgeries. Patients underwent a preoperative sleep study using a portable polysomnography device. Patients with OSA (apnea hypopnea index (AHI) > 5 events/hr), underwent a sleep study on postoperative night 2 (N2) after being randomized into an intervention group (Group I): semi-upright position (30 to 45 degrees incline), or a control group (Group C) (zero degrees from horizontal). The primary outcome was postoperative AHI on N2. The secondary outcomes were obstructive apnea index (OAI), central apnea index (CAI), hypopnea index (HI), obstructive apnea hypopnea index (OAHI) and oxygenation parameters.
RESULTS
Thirty-five patients were included. Twenty-one patients were assigned to the Group 1 (females-14 (67%); mean age 65 ± 12) while there were fourteen patients in the Group C (females-5 (36%); mean age 63 ± 10). The semi-upright position resulted in a significant reduction in OAI in the intervention arm (Group C vs Group I postop AHI: 16.6 ± 19.0 vs 8.6 ± 11.2 events/hr; overall p = 0.01), but there were no significant differences in the overall AHI or other parameters between the two groups. Subgroup analysis of patients with "supine related OSA" revealed a decreasing trend in postoperative AHI with semi-upright position, but the sample size was too small to evaluate statistical significance.
CONCLUSION
In patients with newly diagnosed OSA, the semi-upright position resulted in improvement in obstructive apneas, but not the overall AHI.
TRIAL REGISTRATION
This trial was retrospectively registered in clinicaltrials.gov NCT02152202 on 02/06/2014.
Topics: Female; Humans; Middle Aged; Aged; Prospective Studies; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Polysomnography; Airway Obstruction
PubMed: 37443016
DOI: 10.1186/s12871-023-02193-y -
Frontiers in Psychiatry 2023Hypersomnia poses major challenges to treatment providers given the limitations of available treatment options. In this context, the application of non-invasive brain...
Single sessions of transcranial direct current stimulation and transcranial random noise stimulation exert no effect on sleepiness in patients with narcolepsy and idiopathic hypersomnia.
BACKGROUND
Hypersomnia poses major challenges to treatment providers given the limitations of available treatment options. In this context, the application of non-invasive brain stimulation techniques such as transcranial electrical stimulation (tES) may open up new avenues to effective treatment. Preliminary evidence suggests both acute and longer-lasting positive effects of transcranial direct current stimulation (tDCS) on vigilance and sleepiness in hypersomniac patients. Based on these findings, the present study sought to investigate short-term effects of single sessions of tDCS and transcranial random noise stimulation (tRNS) on sleepiness in persons suffering from hypersomnia.
METHODS
A sample of 29 patients suffering from narcolepsy or idiopathic hypersomnia (IH) was recruited from the Regensburg Sleep Disorder Center and underwent single sessions of tES (anodal tDCS, tRNS, sham) over the left and right dorsolateral prefrontal cortex on three consecutive days in a double-blind, sham-controlled, pseudorandomized crossover trial. The primary study endpoint was the mean reaction time measured by the Psychomotor Vigilance Task (PVT) before and directly after the daily tES sessions. Secondary endpoints were additional PVT outcome metrics as well as subjective outcome parameters (e.g., Karolinska Sleepiness Scale; KSS).
RESULTS
There were no significant treatment effects neither on objective (i.e., PVT) nor on subjective indicators of sleepiness.
CONCLUSION
We could not demonstrate any clinically relevant effects of single sessions of tDCS or tRNS on objective or subjective measures of sleepiness in patients with hypersomnia. However, we cannot exclude that repeated sessions of tES may affect vigilance or sleepiness in hypersomniac patients.
PubMed: 38146280
DOI: 10.3389/fpsyt.2023.1288976 -
Sleep Medicine Sep 2023Psychiatric symptoms and cognitive deficits add significantly to impairment in academic achievement and quality of life in patients with narcolepsy. The primary aim of...
OBJECTIVE/BACKGROUND
Psychiatric symptoms and cognitive deficits add significantly to impairment in academic achievement and quality of life in patients with narcolepsy. The primary aim of this study was to evaluate the prevalence of psychiatric disorders and executive dysfunctions, secondly to explore the association between psychiatric comorbidity, executive dysfunctions, subjective and objective sleep measures, and severity of cerebrospinal fluid (CSF) hypocretin-1 deficiency in pediatric narcolepsy type 1 (PNT1).
PATIENTS/METHODS
Cross-sectional study of 59 consecutively included PNT1 patients (age: 6-20 years; 34:25 girls: boys; 54/59 H1N1 (Pandemrix®)-vaccinated). Core narcolepsy symptoms including subjective sleepiness, polysomnography and multiple sleep latency test results, CSF hypocretin-1 levels, psychiatric disorders (by semistructured diagnostic interview Kaufmann Schedule for Affective Disorders and Schizophrenia Present and Lifetime version (KSADS)), and executive dysfunction (by Behavior Rating of Executive Function (BRIEF)) were assessed.
RESULTS
52.5% of the patients had one or more psychiatric comorbid disorder, and 64.7% had executive dysfunction in a clinically relevant range, with no sex difference in prevalence, while older age was associated with poorer executive function (p=0.013). Having any psychiatric comorbid disorder was associated with poorer executive functions (p=0.001). CSF hypocretin-1 deficiency severity was significantly associated with presence of psychiatric comorbidity (p=0.022) and poorer executive functions (p=0.030), and poorer executive functions was associated with subjective sleepiness (p=0.009).
CONCLUSIONS
The high occurrence of, and association between, psychiatric comorbidity and executive dysfunction underlines the importance of close attention to both these comorbidities in clinical care of NT1.
Topics: Male; Female; Humans; Child; Adolescent; Young Adult; Adult; Orexins; Sleepiness; Cross-Sectional Studies; Influenza A Virus, H1N1 Subtype; Quality of Life; Narcolepsy
PubMed: 37442017
DOI: 10.1016/j.sleep.2023.06.021 -
Sleep Medicine Sep 2023Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been...
OBJECTIVE
Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been suggested to increase the number of hypocretin-producing neurons. We aimed to assess opioid use and its self-reported effect on narcolepsy type 1 symptom severity through a literature review and questionnaire study.
METHODS
We systematically reviewed literature on opioid use in narcolepsy. We also recruited 100 people with narcolepsy type 1 who completed an online questionnaire on opioid use in the previous three years. The main questionnaire topics were the indication for use, and the possible effects on narcolepsy symptom severity. Structured follow-up interviews were conducted when opioid use was reported.
RESULTS
The systematic literature review mainly showed improvements in narcolepsy symptom severity. Recent opioid use was reported by 16/100 questionnaire respondents, who had used 20 opioids (codeine: 7/20, tramadol: 6/20, oxycodone: 6/20, fentanyl: 1/20). Narcolepsy symptom changes were reported in 11/20. Positive effects on disturbed nocturnal sleep (9/20), excessive daytime sleepiness (4/20), hypnagogic hallucinations (3/17), cataplexy (2/18), and sleep paralysis (1/13) were most pronounced for oxycodone (4/6) and codeine (4/7).
CONCLUSIONS
Opioids were relatively frequently used compared to a similarly young general Dutch sample. Oxycodone and, to a lesser extent, codeine were associated with self-reported narcolepsy symptom severity improvements. Positive changes in disturbed nocturnal sleep and daytime sleepiness were most frequently reported, while cataplexy effects were less pronounced. Randomised controlled trials are now needed to verify the potential of opioids as therapeutic agents for narcolepsy.
Topics: Humans; Cataplexy; Analgesics, Opioid; Orexins; Oxycodone; Narcolepsy; Disorders of Excessive Somnolence; Surveys and Questionnaires
PubMed: 37437491
DOI: 10.1016/j.sleep.2023.06.008 -
Scientific Reports Oct 2023The loss of hypocretin is thought to be the main pathophysiological mechanism of narcolepsy. There is strong evidence that hypocretin is related to the regulation of...
The loss of hypocretin is thought to be the main pathophysiological mechanism of narcolepsy. There is strong evidence that hypocretin is related to the regulation of endocrine functions and depression. To explore thyroid hormone levels in narcolepsy patients was our aim. In addition, further is to analyze the relationship between thyroid hormone levels and sleep quality, anxiety, and depression in narcolepsy patients. There are 40 patients with narcolepsy and 40 healthy controls (HCs) were conducted. Blood samples were explored for thyroid function. Correlation analysis between thyroid hormones and clinical characteristics of narcolepsy was performed using Pearson or Spearman. Narcolepsy patients had significantly lower free thyroxine (FT) levels in comparison to controls (p < 0.001). No subject was diagnosed with primary hypothyroidism. There were 4 (10%) subjects with subclinical hypothyroidism. The serum FT4 levels were positively correlated with HAMA score (r = - 0.343, p = 0.030) by Pearson correlation analysis. The serum TSH levels and HAMD score (r = - 0.807 p ˂0.001), and ESS score (r = - 0.317, p = 0.046) both showed a negative correction. Hypocretin deficiency may be associated with the regulation of thyroid hormones in narcolepsy patients. The serum thyroid hormones may affect the severity and neuropsychological functions of narcolepsy patients.
Topics: Humans; Thyroid Gland; Orexins; Thyrotropin; Thyroid Hormones; Narcolepsy; Thyroxine
PubMed: 37898692
DOI: 10.1038/s41598-023-45321-x -
Revista de Neurologia Jul 2023ROHHAD (rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation) is a rare disease, with only about two hundred cases reported to...
INTRODUCTION
ROHHAD (rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation) is a rare disease, with only about two hundred cases reported to date, that starts in previously healthy children. The first sign is usually obesity, followed by hypothalamic dysfunction and sleep-disordered breathing, which rapidly progresses until the death of the patient. ROHHAD with narcolepsy is even rarer, with only two cases described so far.
CASE REPORT
We report the case of a boy who showed signs of obesity and sleepiness since he was 5 years old. At the age of 7, he suffered two tonic-clonic seizures and, over the next four years, displayed signs and symptoms of significant hypothalamic dysfunction; after multiple tests, he was then diagnosed with ROHHAD. Despite receiving a large number of treatments, the patient died at the age of 11.
CONCLUSION
The pathophysiology of this disease needs to be clarified in order to investigate effective treatments in the future.
Topics: Male; Child; Humans; Child, Preschool; Rare Diseases; Autonomic Nervous System Diseases; Hypoventilation; Obesity; Hypothalamic Diseases; Primary Dysautonomias; Narcolepsy
PubMed: 37477027
DOI: 10.33588/rn.77s01.2023196 -
Pharmacology Research & Perspectives Feb 2024Pitolisant, a novel histamine H3-receptor antagonist, holds significant promise for treating narcolepsy. However, a petition, which highlighted that pitolisant was...
Pitolisant, a novel histamine H3-receptor antagonist, holds significant promise for treating narcolepsy. However, a petition, which highlighted that pitolisant was associated with deaths during clinical trials, has propelled it into the spotlight of widespread societal attention on April 3, 2023. Till now, the clinical safety of pitolisant remains a heatedly debated topic. This study aimed to offer a comprehensive assessment of the safety profile of pitolisant in real-world clinical settings. Adverse event reports where pitolisant was the primary suspect drug were extracted from the FDA Adverse Event Reporting System database. The clinical characteristics and concomitant drugs of the pitolisant-associated adverse events were analyzed. The potential adverse event signals of pitolisant were explored using four disproportionality analysis methods. Furthermore, the difference in pitolisant-associated adverse event signals was investigated concerning sex, age, weight, and dose. A total of 526 reports and 1695 adverse events with pitolisant as the primary suspected drug were identified. The most significant adverse event signals were generally mild and of short duration. The concomitant drugs of pitolisant were highly intricate, mainly included drugs for treating narcolepsy as well as antidepressants. Seven new significant adverse event signals emerged. The safety profile of pitolisant exhibited no significant differences across age and dose groups, although slight variations were observed in relation to sex and weight. The findings from reports of death and life-threatening outcomes underscore the importance of enhanced monitoring for cardiac and respiratory adverse reactions when utilizing pitolisant. This study provided a broader understanding of the safety profile of pitolisant.
Topics: Humans; Pharmacovigilance; Retrospective Studies; Narcolepsy; Piperidines
PubMed: 38174838
DOI: 10.1002/prp2.1161