Narcolepsy following COVID-19: A case report and review of potential mechanisms.

Key Clinical Message: The immune activation in COVID-19 may trigger narcolepsy in vulnerable patients. We suggest clinicians carefully evaluate patients with post-COVID fatigue and hypersomnia for primary sleep disorders, specifically narcolepsy. Abstract: The patient is a 33-year-old Iranian woman without a significant past medical history with the full range of narcolepsy symptoms that started within 2 weeks after her recovery from COVID-19. Sleep studies revealed increased sleep latency and three sleep-onset rapid eye movement events, compatible with a narcolepsy-cataplexy diagnosis.

History of sleep. REM sleep and the beginning of sleep medicine: a tribute to Dr. William C. Dement

The emergence of sleep precedes humanity and has always influenced human culture. The modern science of sleep and circadian rhythm medicine is foundationally based to address age old problems such as insomnia and nightmares. The pace of sleep scientific knowledge greatly accelerated with development of all-night sleep recordings and the subsequent illumination of the spectrum of clinical sleep disorders. Much of this fundamental work was influenced by Dr. William C. Dement and several other pioneers described in this article. The history of sleep and circadian science shows us the inexorable, and perhaps destined, path to know the functions of sleep and promote greater sleep health for society. © 2023 Elsevier Inc. All rights reserved

Narcolepsy due to a medical condition

"Narcolepsy due to a medical condition” (symptomatic or secondary narcolepsy) results from a specific underlying medical or neurological condition. Common causes are inherited disorders, tumors, head trauma, demyelinating diseases and stroke. Similar to idiopathic narcolepsy, aberrant T cell mediated cytotoxicity to host antigens in hypocretin neurons might be the underlying pathophysiology. Secondary narcolepsy cases have varying ages of onset, typically following a specific underlying medical or neurological disorder. Primary sleep disorders, mental disorders, or drug/substance use needs to be ruled out. Although the main treatment should be controlling underlying pathologic processes, use of wake promoting medications are often warranted. © 2023 Elsevier Inc. All rights reserved

Impact of Taiwan's 2021 COVID-19 lockdown on the symptom severity and quality of life of patients with narcolepsy.

COVID-19 lockdowns can influence the sleep quality and daytime condition of patients with narcolepsy. Using data from our cohort study, we investigated changes in the quality of life and the symptom severity of patients with narcolepsy during Taiwan's 2021 lockdown and investigated differences by narcolepsy subtype, sex, and age. Patients with type 1 and type 2 narcolepsy (NT1 and NT2, respectively) aged 6-40 years were retrospectively recruited from our narcolepsy cohort study. These patients were regularly evaluated using the Short Form 36 Health Survey questionnaire (SF-36), the Epworth Sleepiness Scale (ESS), the visual analog scale (VAS) for hypersomnolence, the VAS for cataplexy and sleep diary. We compared the differences between the lockdown and the prelockdown periods by narcolepsy subtype, sex, and age. We used a paired t test analysis to compare differences in the SF-36, ESS, VAS scores and data of sleep diary between the prelockdown and lockdown periods (p1), and an independent t test analysis was used to compare the changes in different subgroups between the prelockdown and lockdown periods (p2). A total of 120 patients with narcolepsy were recruited (mean age 24.22 ± 6.87 years; 58% male); 80 of the patients had NT1 (mean age 25.25 ± 6.79 years; 60% male) and 40 had NT2 (mean age 22.16 ± 6.64, 53% male). During the lockdown period, the ESS score of total patients was decreased (p = 0.039) and body mass index was increased (p = 0.02). The NT1 group decreased significantly (p1 = 0.017), especially in men (p1 = 0.016) and adults (p1 = 0.04); scores for the VT domain of the SF-36 increased significantly in male and adult patients with NT2 (p1 = 0.048 and 0.012). Additionally, male patients with NT2 exhibited significantly decreased scores in the physical and emotional role functioning domains (p1 = 0.028, 0.024). The children and adolescents with NT1 had significantly decreased scores in the general health domain of the SF-36, but no significant change was noted in that of adults (p1 = 0.027, p2 = 0.012). We observed both negative and positive impacts of Taiwan's 2021 lockdown on patients with narcolepsy. A more flexible but structured daily routine with adequate sleep time should be considered for this population during lockdown and nonlockdown periods.

Contemporary Concise Review 2022: Sleep.

COVID-19 AND SLEEP: The COVID-19 pandemic is associated with an increase in insomnia and impaired sleep quality Health care workers are particularly susceptible and improved with cognitive behavioural therapy for insomnia (CBT-I) Long COVID has significant effects on sleep OSA impacts on the severity of acute COVID-19 illness OBSTRUCTIVE SLEEP APNOEA: Large trials of clinically representative patients confirm the cardiovascular benefits of CPAP treatment in OSA CPAP may improve long-term cognitive outcomes in OSA, but further research is needed Racial disparities in OSA prevalence and mortality risk are becoming evident Periodic evaluation of OSA risk in pregnancy is important as timing may be key for intervention to prevent or treat cardiovascular risk factors INSOMNIA: Comorbid insomnia and obstructive sleep apnoea (COMISA) can frequently co-exist and the combined negative effects of both may be deleterious, particularly to cardiovascular health There is evidence for effectiveness with novel orexin receptor antagonists.

Multidisciplinary care of patients with narcolepsy during COVID-19 pandemic in Italy via televisit: the TElemedicine for NARcolepsy (TENAR) feasibility study.

STUDY OBJECTIVES: Narcolepsy is a rare chronic central disorder of hypersomnolence with frequent endocrine-metabolic comorbidities. To address the complex care needs of patients during the COVID-19 emergency, we carried out a feasibility study of the TElemedicine for NARcolepsy (TENAR) protocol with the aim of assessing the feasibility of a multidisciplinary care approach via televisit for patients with narcolepsy. METHODS: A feasibility single open arm study on the multidisciplinary care of children (>7 y.o.) and adults with narcolepsy who required a follow-up visit was realized during the COVID-19 pandemic emergency period in Italy. The study included a sleep, metabolic, and psychosocial assessment via televisit at baseline, at 6, and at 12 months from the study inclusion period (15 th May - 26 th June 2020). RESULTS: Thirty-nine out of 44 eligible patients (89%) entered the study (30 adults, nine children); 37 patients (95%) ended the 12-month follow-up. At baseline, the median Epworth sleepiness scale score (ESS) was 10 (IQR 8-14), and the median body mass index (BMI) was 25.6 (IQR 22.1-30.9). During the follow-up period, the ESS score decreased from the 6th month onward (p=0.003), and BMI decreased at the 1-year follow-up (p=0.047), while there were no differences in depressive and anxiety symptoms, quality of life, compliance with treatment, adverse drug reactions, or accidents. CONCLUSION: High response and retention rates, stability of ESS and lack of side effects indicate that telemedicine is a feasible and safe approach for adults and children with narcolepsy.

Central hypersomnia and chronic insomnia: expanding the spectrum of sleep disorders in long COVID syndrome - a prospective cohort study.

INTRODUCTION: Long-onset COVID syndrome has been described in patients with COVID-19 infection with persistence of symptoms or development of sequelae beyond 4 weeks after the onset of acute symptoms, a medium- and long-term consequence of COVID-19. This syndrome can affect up to 32% of affected individuals, with symptoms of fatigue, dyspnea, chest pain, cognitive disorders, insomnia, and psychiatric disorders. The present study aimed to characterize and evaluate the prevalence of sleep symptoms in patients with long COVID syndrome. METHODOLOGY: A total of 207 patients with post-COVID symptoms were evaluated through clinical evaluation with a neurologist and specific exams in the subgroup complaining of excessive sleepiness. RESULTS: Among 189 patients included in the long COVID sample, 48 (25.3%) had sleep-related symptoms. Insomnia was reported by 42 patients (22.2%), and excessive sleepiness (ES) was reported by 6 patients (3.17%). Four patients with ES were evaluated with polysomnography and test, multiple sleep latencies test, and actigraphic data. Two patients had a diagnosis of central hypersomnia, and one had narcolepsy. A history of steroid use was related to sleep complaints (insomnia and excessive sleepiness), whereas depression was related to excessive sleepiness. We observed a high prevalence of cognitive complaints in these patients. CONCLUSION: Complaints related to sleep, such as insomnia and excessive sleepiness, seem to be part of the clinical post-acute syndrome (long COVID syndrome), composing part of its clinical spectrum, relating to some clinical data.

Distinguer la narcolepsie de type 2, l’hypersomnie idiopathique, la dépression et la somnolence dans le syndrome post-COVID-19

Résumé Les syndromes d’hypersomnolence d’origine centrale (c.-à-d. narcolepsie de type-1, narcolepsie de type-2 et hypersomnie idiopathique), la dépression ainsi qu’un sous-type du syndrome post-COVID-19 peuvent être confondus lors de l’établissement d’un diagnostic. Ce défi diagnostique s’explique par un symptôme clinique caractéristique retrouvé dans les quatre conditions, la somnolence diurne excessive, un chevauchement phénotypique considérable entre la narcolepsie de type-2 et l’hypersomnie idiopathique ainsi qu’une symptomatologie dysphorique pouvant être présente autant dans les hypersomnolences centrales que dans un sous-type du syndrome post-COVID-19. Considérant l’importance d’un diagnostic valide sur l’efficacité des traitements et des interventions futures, il est essentiel de définir précisément ces quatre conditions. Dans cette revue, nous reprendrons les critères diagnostiques, les présentations cliniques et les connaissances actuelles en ce qui a trait à la pathophysiologie de ces troubles en portant une attention particulière aux éléments distinctifs de la narcolepsie de type-2, de l’hypersomnie idiopathique, des épisodes dépressifs avec hypersomnolence et du syndrome post-COVID-19 avec somnolence. Bien que de nombreuses études se soient penchées sur les valeurs diagnostiques des différents outils employés dans l’identification des hypersomnolences centrales, très peu de marqueurs physiologiques ont été identifiés. Une meilleure compréhension de ces conditions cliniques pourrait permettre l’identification de marqueurs objectifs spécifiques à chaque condition réduisant ainsi la possibilité d’une erreur diagnostique et optimisant les plans de traitement. Summary Central disorders of hypersomnolence, including narcolepsy type-1 and type-2 as well as idiopathic hypersomnia, depression and a subtype of post-acute COVID-19 syndrome might be confused when establishing a diagnosis. This diagnostic challenge can be explained by the presence of excessive daytime sleepiness, a clinical symptom that is observed in all four conditions, an overlap in the phenotypic traits of narcolepsy type-2 and idiopathic hypersomnia, as well as the presence of depressive symptoms observed in central disorders of hypersomnolence and post-acute COVID-19 syndrome subtypes. Considering the importance of a valid diagnostic on treatment's efficacy and future interventions, it is essential to define those conditions with precision. In this review, we will discuss the diagnostic criteria, clinical presentation and current state of knowledge with regards to the pathophysiology of central disorders of hypersomnolence and post-acute COVID-19 syndrome. We will pay particular attention to the characteristics specific to narcolepsy type-2, idiopathic hypersomnia, depressive episodes with hypersomnolence, and post-acute COVID-19 syndrome with drowsiness. While many studies have assessed the ability of different tools used to diagnose central disorders of hypersomnolence, very few have focused on physiological markers. A better understanding and identification of biomarkers specific to narcolepsy type-1 and type-2, idiopathic hypersomnia and post-acute COVID-19 syndrome will reduce the possibility of misdiagnoses and allow the development of optimal treatment plans.

The risk of neurological diseases after COVID-19, influenza A/B or communityacquired pneumonia infection

Background and aims: Two years after onset of the pandemic, the precise nature and temporal evolution of the effects of COVID-19 on neurologic disorders remain uncharacterized. Studies have established an association with neurological syndromes, including anosmia, encephalopathy, and ischemic stroke, but it is unknown whether COVID-19 also influences the incidence of specific neurologic diseases and whether it differs from other respiratory infections. Methods: Using population-based electronic health records we investigated the association between COVID-19 and specific central and peripheral neurologic diseases. We compared patients with COVID-19 to individuals without, and to patients with influenza A/B and community-acquired bacterial pneumonia. We assessed the incidence of neurologic disease one, three, six, and twelve months after positive test results. Results: We identified 42,535 people with COVID-19, 8,329 with influenza, 1,566 with pneumonia, and 2,392,400 without COVID-19. Compared to individuals without COVID-19, patients with COVID-19 had increased relative risk (RR) of developing Guillain Barré syndrome (RR=3.1;95% CI=1.5-6.7), multiple sclerosis (RR=1.4;95% CI=1.2-1.7), narcolepsy (RR=3.2;95% CI=1.6-6.2), Parkinson's disease (RR=2.8;95% CI=2.4-3.2), Alzheimer's disease (RR=4.9;95% CI=4.0-6.0), dementia of any type (RR=5.2;95% CI=4.5-6.1), and ischemic stroke (RR=2.3;95% CI=2.1-2.5). However, compared to patients hospitalized with influenza, patients hospitalized with COVID-19 only had an increased risk of ischemic stroke at one (RR=1.9;95% CI=1.3-2.8), three (RR=1.8;95% CI=1.3-2.5) and six months (RR=1.9, 95% CI=1.3-2.7). Compared to patients hospitalized with pneumonia, the risk of neurologic diseases was not increased. Conclusion: COVID-19 increases the risk of a broad range of neurological disorders. However, except for ischemic stroke, there is no excess risk compared to influenza A/B and community-acquired pneumonia.

Experience with over 10,000 sleep telemedicine visits for diagnosis and treatment of OSAS

Introduction: Since March 2020 BlueSleep has completed over 10,000 telemedicine consultations for diagnosis and treatment of sleep apnea exclusively by real-time telemedicine consultations using HIPAA-compliant video conferencing. Materials and Methods: This is a retrospective chart review of all virtual consultations performed between March 13, 2020 and December 31, 2021 at the BlueSleep center. This period coincided with the lockdown in New York City because of the COVID19 Pandemic. 10,171 telemedicine consultations were performed both for new and existing patients. No patients under the age of 18 were evaluated. The median patient age was 40 years old;2,412 males, 1,098 females. Diagnosis of sleep apnea was performed with disposable single-night or multi-night Home Sleep Tests (HST) with WatchaptOne (Itamar Medical) or Nightowl (Ectosense). Patients were given instructions for HSTs via asynchronous videos. HST data was transmitted to a portal for scoring and interpretation. Follow-up visit was by telemedicine, and treatment options including oral appliance therapy and CPAP were discussed. Surgical options were not available during the lockdown. If oral appliance therapy was chosen by the patient, a virtual visit with a dental professional was scheduled before sending a home impression kit. Home impressions were guided in real time with a dental professional. Dental impressions were submitted to the dental labs for fabrication of Mandibular Advancement Devices (MAD), and sent to the patient for a virtual home delivery by the dental professionals. A follow-up virtual visit was scheduled after the 4-week titration period, and depending on subjective results of decreased snoring and decreased daytime sleepiness, the patient was then instructed to repeat a HST for efficacy evaluation. If the patient chose CPAP, CPAP was shipped to the home, and a follow-up visit was scheduled for a virtual set-up visit, followed by compliance visits. All patients were scheduled for continuous telemedicine follow-up visits. Results: 10,171 visits were completed including first and follow-up visits. A total of 289 single-night and 2,275 multi-night HSTs were performed. 2,348 patients were diagnosed with OSA. 36% with mild OSA, 41% of patients with moderate OSA, and 23% with severe OSA. 1,163 had no OSA. 53% of patients were treated with OAT, 20% with CPAP. 271 patients were treated for primary snoring. 256 patients were treated for insomnia. 31 patients were diagnosed with Narcolepsy, and 636 patients were diagnosed with "other". Conclusions: A fully virtual model for diagnosis and treatment for obstructive sleep apnea and other sleep disorders is feasible and desirable. Telemedicine allows greater convenience (less time lost from work), and availability (greater geographic availability), and is a lower cost option. Acknowledgements: We wish to thank the entire BlueSleep staff that has helped make our service to patients available during the Covid 19 Pandemic.

Sleep disturbances in craniopharyngioma: a challenging diagnosis

Introduction: The hypothalamus plays a crucial role in regulating vital functions and circadian rhythms. Both the tumor involving the hypothalamic area and its treatment can lead to hypothalamic dysfunction, resulting in disturbances in sleep-wake patterns, sleep fragmentation, and increased daytime sleepiness. We describe two patients with craniopharyngioma who came to our attention due to the occurrence of episodes characterized by psychomotor slowing and afinalistic limb movements, temporal and spatial disorientation, psychomotor agitation, and oneiric stupor like episodes diagnosed as severe sleep disturbances. Case reports: Patient 1 is a 19-year-old male diagnosed with surgically treated craniopharyngioma. Subsequently, episodes of psychomotor slowing, afinalistic movements of the upper limbs diagnosed as seizures in another neurological center appeared;antiepileptic treatment was started without improvement. At the first examination in our center, excessive daytime sleepiness (EDS), fragmented nighttime sleep, episodes characterized by bimanual automatic gestures occurring during drowsy state, hypnagogic hallucinations, and sudden loss of muscle tone while awake were recognized. Actigraphy demonstrated irregular bedtimes, frequent nocturnal activity, and inappropriate daytime rest episodes. The Epworth Sleepiness Scale (ESS) showed subjective EDS (ESS=19). At PSG, hypersomnolence, severe sleep-related breathing disorder (SRBD), and no interictal and ictal seizure abnormalities were found. A BiPAP NIV was started, and antiepileptic therapy was discontinued. In the following months, PSG revealed marked improvement in SRBD and 1 SOREMP, and the MSLT a mean SOL of 6 min and 10 sec and 3 SOREMPs. These data allowed the diagnosis of secondary narcolepsy, and treatment with pitolisant was initiated with clinical improvement and reduced daytime sleepiness (ESS=9). Patient 2 is a 12-year-old male, surgically treated for craniopharyngioma at the age of 4 years, who developed episodes of myoclonic jerks, temporal and spatial disorientation, and psychomotor agitation during the lockdown period for COVID-19 emergency. Surmising paroxysmal epileptic episodes, the patient was hospitalized. The anamnestic data collection revealed a sleep-wake rhythm dysregulation, fragmented nighttime sleep, EDS, oneiric stupor-like episodes during which the patient performed simple automatic gestures mimicking daily-life activity, and severe impairment of alertness. The Long-term video-EEG, including polygraphic measurements, showed destruction of the wake-NREM sleep-REM sleep boundaries, episodes of undetermined state of vigilance, and concurrence of elements typical of different sleep stages. Moreover, a severe SRBD (AHI 19/h) has been observed. The MRI showed a volumetric increase in the post-surgical interpeduncular fossa and right paramedian cysts. Therefore, a multifactorial therapeutic plan including sleep hygiene and slow-release melatonin was started with improvement in nighttime sleep, but EDS persisted. Surgical treatment of cyst fenestration improved sleep-wake rhythm and behavior;BiPAP NIV was initiated with very poor adherence. Discussion: We aim to focus on sleep disorders as a possible complication of tumors involving the hypothalamic region. Our cases highlight that the clinical manifestation of these dysfunctions can be challenging to diagnose and can lead to misdiagnosis and inappropriate treatment that can harm patients' health and the quality of life of patients and their families. Conclusion: These findings support the need to incorporate comprehensive sleep assessment in survivors from childhood brain tumors involving the suprasellar/hypothalamic region.

COVID-19 and Central Nervous System Hypersomnias.

Purpose of review: Central nervous system (CNS) hypersomnias can be triggered by external factors, such as infection or as a response to vaccination. The 2019 coronavirus disease (COVID-19) pandemic, which was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to a worldwide effort to quickly develop a vaccine to contain the pandemic and reduce morbidity and mortality. This narrative review is focused on the literature published in the past 2 years and provides an update on current knowledge in respect of the triggering of CNS hypersomnias by infection per se, vaccination, and circadian rhythm alterations caused by social isolation, lockdown, and quarantine. Recent findings: At present, there is no consensus on the association between hypersomnias and COVID-19 vaccination or infection per se; however, the data suggest that there has been an increase in excessive daytime sleepiness due to vaccination, but only for a short duration. Kleine Levin syndrome, hypersomnia, excessive daytime sleepiness, and narcolepsy were aggravated and exacerbated in some case reports in the literature. Both increased and decreased sleep duration and improved and worsened sleep quality were described. In all age groups, delayed sleep time was frequent in studies of patients with hypersomnolence. Summary: The hypothesis that there is a pathophysiological mechanism by which the virus, vaccination, and the effects of quarantine aggravate hypersomnias is discussed in this review.

The Impact of Sleep Pattern in School/Work Performance During the COVID-19 Home Quarantine in Patients With Narcolepsy.

Objectives: Narcolepsy patients were observed improvements in their academic performance during the COVID-19 home quarantine. Therefore, we aim to investigate the influence of sleep behavioral changes on school/work performance in narcolepsy patients during the home quarantine. Methods: Patients admitted to Shandong Provincial Qianfoshan Hospital from Jan 1, 2017 to Jan 1, 2021 who were diagnosed with narcolepsy were studied by online questionnaires in two different periods (during and 1 year after the COVID-19 home quarantine), including five aspects: (1) changes in school/work performance (percentile ranking in class/Sheehan Disability Scale 1, SDS1); (2) daytime functions; (3) clinical symptoms; (4) psychological moods; (5) medication situations. Results: A total of 46 narcolepsy patients 34 (73.9%) narcolepsy type 1, 12 (26.1%) narcolepsy type 2 with average age of 20.76 ± 8.99 years and an equal number of age and gender matched control subjects were enrolled. During the COVID-19 home quarantine, the narcolepsy patients were found that they altered sleep patterns, including later get up time (P < 0.001), longer total sleep time (TST, P = 0.001), better sleep quality (PSQI, P = 0.001), and lower anxiety level (P = 0.005). Their school/work performance improved parallelly [with better percentile ranking (P = 0.001) and lower SDS1 scores (P = 0.002)]. The results of multiple linear stepwise regression analysis showed a linear regression relationship between TST [efficient (95%) -7.356 (-13.570 to 1.143)], SDS1 score [efficient (95%) 6.580 (2.346-10.815), P = 0.004] and the percentile ranking after adjusting for potential effects. Both the improvements of sleep behavior and school/work performance disappeared after the end of COVID-19 home quarantine. No similar fluctuation was found in the control group. Discussion: Changes in sleep pattern during the COVID-19 home quarantine, such as longer sleep time and later wake-up time, can reduce the degree of daytime sleepiness and increase the degree of daytime wakefulness of narcolepsy patients, which can alleviate the impact of the disease on school/work performance.

Pfizer/BioNTech SARS-CoV-2 vaccine as a potential trigger for the development of narcolepsy: a case report.

Narcolepsy is a rare condition in Israel. Currently, the incidence of narcolepsy following SARS-CoV-2 vaccination in Israel is unknown. We are reporting a case report of a 51-year-old woman of Ashkenazi Jewish descent who was evaluated for complaints of excessive daytime sleepiness and relative functional decline that immediately followed receipt of the Pfizer/BioNTech SARS-CoV-2 vaccination. Evaluation of patient-reported data with polysomnography and multiple sleep latency test was consistent with narcolepsy with cataplexy, meeting the criteria for a diagnosis of type 1 narcolepsy. Further investigation included human leukocyte antigen testing. Prior studies have demonstrated genetic, immunological, and environmental factors associated with narcolepsy following other vaccinations. This case is a valuable contribution to the literature as there are no prior reports of type 1 narcolepsy following SARS-CoV-2 vaccination in the State of Israel. CITATION: Mahamid A, Bornstein RJ, Amir H. Pfizer/BioNTech SARS-CoV-2 vaccine as a potential trigger for the development of narcolepsy: a case report. J Clin Sleep Med. 2022;18(10):2503-2506.

Reactogenic sleepiness after COVID-19 vaccination. A hypothesis involving orexinergic system linked to inflammatory signals.

Coronavirus disease 2019 (COVID-19) represents a global healthcare crisis that has led to morbidity and mortality on an unprecedented scale. While studies on COVID-19 vaccines are ongoing, the knowledge about the reactogenic symptoms that can occur after vaccination and its generator mechanisms can be critical for healthcare professionals to improve compliance with the future vaccination campaign. Because sleep and immunity are bidirectionally linked, sleepiness or sleep disturbance side effects reported after some of the COVID-19 vaccines advise an academic research line in the context of physiological or pathological neuroimmune interactions. On the recognized basis of inflammatory regulation of hypothalamic neurons in sickness behavior, we hypothesized that IL-1ß, INF-γ and TNF-α pro-inflammatory cytokines inhibit orexinergic neurons promoting sleepiness after peripheral activation of the innate immune system induced by the novel COVID-19 vaccines. In addition, based on knowledge of previous vaccines and disease manifestations of SARS-CoV-2 infection, it also suggests that narcolepsy must be included as potential adverse events of particular interest to consider in pharmacovigilance studies.

Mechanistic Episodes on SARS-CoV-2 Mediated Neurological Manifestations and Their Possible Therapeutic Interventions

Recently, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been critically recognized and spread rapidly on this planet. Considerable recognition of SARS-CoV-2 has been known with a range of viruses that are more capable to cause diseases in avian and mammals including humans. The virus was found as a main culprit for major defects in respiratory system and thereby caused severe acute respiratory syndrome disease. This has led to depict the mortality in human population. Nevertheless, compromised reports on SARS-CoV-2 has also shown neurological complications in both central nervous system (CNS) and peripheral nervous system (PNS). This virus has notified with neurological defects as stroke, encephalopathy, cerebral edema, erythema, seizures, meningitis, ischemic, agcusia, loss of smell, myalgia and Guillain Barre Syndrome. In this review, we focused on COVID-19 mediated neurodegerieration and its mechanistic episodes on affected patients. We also discuss the possible available therapeutic interventions with clinically investigated drugs against COVID-19 mediated neurological impairment in patients and experimental in vitro and in vivo research models required for the development of drugs and/or vaccines against COVID-19 mediated neurological complications.

Two sides of a coin: differential response to COVID-19 distancing measures in children with narcolepsy.

NONE: Narcolepsy is a chronic neurological sleep disorder, debuting before age 15 years in one-third of patients. Narcolepsy has a negative influence on quality of life, with daily functioning being affected by concomitant cognitive, behavioral, and social problems. In December 2019, a new coronavirus emerged worldwide, causing the severe respiratory disease COVID-19. In the Netherlands, a partial lockdown was implemented that included the closure of schools. Here we present 3 illustrative case reports that teach important lessons for the treatment of pediatric narcolepsy. We observed significant consequences of the partial lockdown measures on daytime functioning, well-being, and school performance, both negative and positive. The consequences of the lockdown led to valuable insights for further treatment, substantiating the importance of personalizing education. Involvement of specialized student counselors, flexibility in the way that education is delivered, and enhancement of environmental factors could help in guiding young patients with narcolepsy through challenges at school.

Being creative during lockdown: The relationship between creative potential and COVID-19-related psychological distress in narcolepsy type 1.

The national lockdown imposed in several countries to counteract the coronavirus disease 2019 (COVID-19) pandemic led to an unprecedented situation with serious effects on mental health of the general population and of subjects affected by heterogeneous diseases. Considering the positive association between narcoleptic symptoms and creativity, we aimed at exploring the psychological distress associated with COVID-19 restrictions and its relationship with depressive symptoms and creativity in patients with narcolepsy type 1 (NT1). A total of 52 patients with NT1 and 50 healthy controls, who completed a previous study on creativity, were contacted during the first lockdown period to complete an online survey evaluating psychological distress related to the COVID-19 outbreak, sleep quality, narcolepsy and depressive symptoms, and creative abilities. The patients with NT1 showed an improvement in subjective sleepiness while controls reported worsening of sleep quality during the lockdown. Depression and NT1 symptom severity proved significant predictors of COVID-19-related distress. Creative performance, namely generative fluency, turned out to be a favourable moderator in the relationship between depression and patients' distress, reducing the detrimental effect of depression on the patients' wellbeing. On the contrary, creative originality proved to be a disadvantageous moderator in the relationship between NT1 symptom severity and the distress associated with this traumatic event indicating a higher vulnerability to developing COVID-19-related distress, particularly evident in patients displaying higher originality. Overall, these results highlight a crucial role of creativity in patients with NT1, suggesting that creative potential could be used as a protective factor against the development of distress associated with the lockdown.

Sleeping through a pandemic: impact of COVID-19-related restrictions on narcolepsy and idiopathic hypersomnia.

STUDY OBJECTIVES: To assess the impact of coronavirus disease 2019 (COVID-19)-related restrictions on narcolepsy type 1 (NT2), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH). METHODS: Participants with NT1, NT2, and IH followed in a university hospital completed an online 78-question survey assessing demographic, clinical, and occupational features of the population during the first COVID-19-related lockdown. RESULTS: A total of 219 of 851 (25.7%) respondents of the survey reported a mean increase of 1.2 ± 1.9 hours (P < .001) in night sleep time and a mean decrease of 1.0 ± 3.4 points (P < .001) on the Epworth Sleepiness Scale during lockdown. Bedtime was delayed by 46.1% of participants and wakeup time was delayed by 59.6%, driven primarily by participants with IH. Teleworkers (but not in-person workers) reported a mean increase of 0.9 ± 1.2 hours in night sleep (P < .001) and a mean decrease in sleepiness score of 1.6 ± 3.1 (P < .001). Cataplexy improved in 54.1% of participants with NT1. Sleepiness correlated with psychological wellness (r = .3, P < .001). As many as 42.5% enjoyed the lockdown, thanks to reallocation of time usually spent commuting toward longer sleep time, hobbies, and family time, and appreciated a freer napping schedule. Conversely, 13.2% disliked the lockdown, feeling isolation and psychological distress. CONCLUSIONS: Extended sleep time, circadian delay (in patients with IH), and teleworking resulted in decreased symptoms of central hypersomnias. These findings suggest that people with IH, NT1, and NT2 may benefit from a decrease in social and professional constraints on sleep-wake habits, and support advocacy efforts aimed at facilitating workplace and schedule accommodations for this population. CITATION: Nigam M, Hippolyte A, Dodet P, et al. Sleeping through a pandemic: impact of COVID-19-related restrictions on narcolepsy and idiopathic hypersomnia. J Clin Sleep Med. 2022;18(1):255-263.