bluuebunny/crossref_metadata_2025 huggingface dataset:
1022 Two Teenagers with New Onset Insomnia post COVID
Authors: Popoola Taiye , Wani Anna , Srikrishnan Anand , Rovira Elisa Basora
Published: May 2023

Introduction

Sleep disturbances are increasingly seen in COVID-19 infection. Multiple reports have described the onset of insomnia, excessive daytime sleepiness, and fatigue in patients with both acute COVID infection and long COVID syndrome. Most of these are limited to adults. We report the cases of 2 teenagers with new onset chronic insomnia post COVID-19 infection.

Report of case(s)

The first patient is a 14-year-old male who presented with sleep onset and sleep maintenance insomnia, excessive daytime sleepiness, difficulty concentrating, fatigue, and chronic cough, with onset five months prior presentation to the sleep clinic. He developed these symptoms after testing positive for COVID-19. He had significant impairment with multiple school absences and tardies for which he required accommodation. He completed a 2-week actigraphy test which showed prolonged sleep latencies and insufficient sleep. He was scheduled for polysomnography (PSG) followed by a multiple sleep latency test (MSLT) but could not proceed to MSLT due to insufficient sleep the night before. The PSG did not reveal either obstructive sleep apnea or periodic limb movements of sleep. His laboratory testing was significant for a low ferritin level of 21. He was referred for IV iron infusion due to intolerance for oral iron. He was started on melatonin without benefit. He was offered clonidine and trazodone but declined. The second patient, a 17-year-old male, presented with insomnia of 3 months duration which started after an acute COVID infection. In addition to insomnia, he had comorbid mood symptoms. He went from being engaged in school and work to being unmotivated and listless. His actigraphy testing revealed he was having sufficient sleep on several days during which he reported not getting any sleep. He failed trials of multiple medications including melatonin, trazodone, hydroxyzine, and gabapentin. He also denied benefit with CBT-I.

Conclusion

These case reports link COVID 19 and chronic insomnia in pediatric patients. While it is yet unclear whether the development of sleep disturbances post COVID is as a result of an intrinsic characteristic of the COVID-19 virus or the biopsychosocial effects of the pandemic, it is important to develop and implement targeted interventions focused on recognizing and treating insomnia early.

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1025 Schizophrenic Patient with Large REM Rebound Following Treatment of Severe Obstructive Sleep Apnea
Authors: Qasmi Syed Talha , Aguillon Andre
Published: May 2023

Introduction

We present a case of uncontrolled schizophrenia with severe obstructive sleep apnea (OSA) and significant REM rebound after bilevel positive airway pressure (BPAP) therapy.

Report of case(s)

A 74-year-old female, with Schizophrenia on anti-psychotic therapy, presented to the sleep clinic due to excessive daytime sleepiness (EDS) and an Epworth score of 21/24. Diagnostic polysomnogram (PSG) reported an AHI of 162.1 events/hour with SaO2 nadir of 71% with sleep efficiency of 31.6% and no REM-sleep, consistent with severe OSA. The next morning, multiple sleep latency testing (MSLT) demonstrated mean sleep latency (MSL) of 3.6 minutes with 0 REM-onset sleep periods (SOREMPs). Patient underwent CPAP/BPAP titration which improved sleep efficiency to 88.6% and severe REM rebound at 61.7%. MSLT after the titration study demonstrated MSL of 4.0 minutes and 3 SOREMPs and was initiated on BPAP therapy at 20/13 cmH2O. A repeat PSG, 4 weeks later showed normalization of sleep architecture. After starting PAP therapy, the patient had a significant improvement in EDS but also energy and interest levels and denied feelings of sadness, racing or paranoid thoughts. Her social life improved and started exercising regularly and volunteering in the community. There was also improved blood pressure and blood sugar levels. She was followed up in the sleep clinic regularly and remained compliant with and benefiting from BPAP therapy and was continued on anti-psychotic therapy.

Conclusion

Untreated OSA often requires repetitive arousals to reopen the obstructed upper-airway that results in increased non-REM sleep at the expense of slow wave sleep and REM sleep. PAP therapy can cause a rebound increase in REM and SWS. OSA is under recognized in schizophrenic patients and other psychiatric disorders which results in development of significant comorbidities with greater severity of psychiatric symptoms. Elevated rates of OSA have been seen in the schizophrenic population. Treatment of OSA helps with not only physical but also psychotic symptoms. Many anti-psychotics, due to causing weight gain, may contribute to OSA. Studies also indicated that CPAP response to OSA, was as favorable in people with severe mental illness, compared to other patient groups.

Support (if any)

REM rebound and CPAP compliance; B. Koo, R. Wiggins, C. Molina
1026 Severe Sleep Inertia Managed with Bupropion
Authors: Qasmi Syed Talha , Cavins Gayle , Rulong Geoffrey
Published: May 2023

Introduction

Severe sleep inertia (SI) can often be managed with behavioral modifications and stimulants. This patient’s sleep inertia was resistant to such therapies but had remarkable improvement with Bupropion.

Report of case(s)

An 11-year-old male with a history of seizures presented with hypersomnolence, SI and difficulty arousing in the morning for 3 years. There was no reported cataplexy, with occasional hypnogogic hallucinations and sleep paralysis. Family denied witnessed apneas or snoring. He had previously undergone an adenotonsillectomy at 6 years of age for obstructive sleep apnea. When initially seen, he was not taking antiseizure medications, Epworth score was 14 and BMI was 30.5 kg/m2. Polysomnogram showed an AHI of 1.5 events/hour with REM latency of 179.5 minutes. Multiple sleep latency testing showed a mean sleep latency of 4 minutes, 7 seconds with 3 SOREM periods: consistent with narcolepsy. Melatonin and methylphenidate were initially prescribed, followed by dextroamphetamine-amphetamine, but were discontinued due to worsening hypersomnolence. Armodafinil improved his overall daytime sleepiness, however, severe SI persisted intermittently in the morning and with naps to the point of EMS being called on multiple occasions. EEG and brain-MRI were normal. For suspected cataplexy, venlafaxine was tried and not beneficial. Calcium-magnesium-potassium and sodium oxybate (XW) lead to no improvement in his SI. Therefore, Methylphenidate-20mg (MP) and then Armodafinil-50mg were added before bedtime, however, his SI persisted with frequently missed school. Bedtime Bupropion 150 mg was added with an immediate response. He has not missed school or daytime activities with Bupropion.

Conclusion

Sleep inertia is typically a characteristic of idiopathic hypersomnia rather than narcolepsy and is related to the abnormal transition of sleep to wakefulness resulting in reduced alertness, impaired performance, and desire to return to sleep. Such pronounced sleep inertia is atypical and caused significant quality of life impairment in our patient. Nighttime melatonin, XW, MP, and bupropion for SI has been described in the literature1. Our patient failed multiple treatments before bupropion which was immediately successful.

Support (if any)

1. Treatment of severe morning sleep inertia with bedtime long-acting bupropion and/or long-acting methylphenidate in a series of 4 patients. Schenck, MD1 ; Golden, MD2 ; Millman, MD3
1028 Congenital Central Hypoventilation in a patient with MCEP2 duplication syndrome
Authors: Rehman Sofiya , Srikrishnan Anand , Wani Anna
Published: May 2023

Introduction

Congenital central hypoventilation (CCHS) is a rare disorder due to impairment of autonomic nervous system clinically defined by a significantly reduced or abolished ventilatory response to hypercapnia and hypoxemia in the absence of pulmonary, neuromuscular, or cardiac disease. There is limited knowledge on associated respiratory manifestations and sleep-disordered breathing in children with the MECP2 duplication syndrome. Although sleep-disordered breathing and nocturnal hypoventilation are currently not well recognized in these children, we present a case of a patient with MECP2 mutation and congenital hypoventilation syndrome.

Report of case(s)

24-week-old male born full-term via c-section presented with recurrent respiratory problems, laryngeal cleft, dysphagia, snoring and apneic episodes. Previous genetic work up showed chromosome 15q11.2 microdeletion. Past medical history was significant for neonatal ICU stay for respiratory distress immediately following birth. Tonsils are 1+ on exam. PSG showed profound central sleep apnea (CAI 300/h) with average apneic episodes lasted for 7 seconds and very significant periodic breathing (88%) and mild obstructive apnea. Mild hypoxemia was also seen with SpO2 in low 90s without any significant hypercapnia. Bradypnea with resp rate 10-20/m was seen. PHOX2B gene testing was negative. Genetic testing with SNP array showed MECP2 duplication syndrome. His development is delayed, currently at the age of 20 months, including cognitive, speech and motor function for which he is on therapy. Tracheostomy was recommended, however family preferred to continue with non-invasive ventilation while awaiting diaphragmatic pacing.

Conclusion

Respiratory manifestations in MECP2 duplication syndrome patients are common, with important impact and even a possible fatal outcome. Although sleep-disordered breathing and nocturnal hypoventilation is currently not cited as an important symptom in these children, there have been several case reports of CCHS associated with this. PSG should be considered in patients with MCEP2 duplication syndrome for timely diagnosis. Different treatment modalities (ENT surgery, CPAP and NIV) can be applied successfully to treat respiratory conditions associated with MECP2 duplication syndrome.

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1030 Alice in wonderland: A rare side effect of montelukast
Authors: Rojas Edward , Stansbury Robert , Azzouz Mouhannad , Sharma Sunil , Pham Christopher , Coutras Steven , Clawges Heather
Published: May 2023

Introduction

Alice in wonderland syndrome (AIWS), also known as Todd’s syndrome, is a neuropsychological condition that causes a set of symptoms with alteration of body image. These distortions include appearing smaller(micropsia) or larger(macropsia) or appearing to be closer or farther than they are. The exact cause of AIWS is currently unknown. Some associations include, migraine, temporal lobe epilepsy, brain tumors, psychoactive drugs or Epstein-Barr-virus. The treatment for this disease primarily aims at treating the underlying reason as to why the patient had the event.

Report of case(s)

7-year-old boy presents to sleep clinic for nighttime hallucinations. Nightly episodes described as body parts that seem abnormally large or small and people talking very fast. Events lasted 15 minutes. Patient had full recall and developed anxiety when falling asleep. Medications at presentation: vitamins, melatonin, Montelukast. Montelukast was discontinued. Referred to neurology for video EEG, which was negative for frontal lobe seizures. Due to restless sleep and snoring, sleep study and ferritin was ordered. He was found to have mild OSA with an AHI of 2.2 and a ferritin level of 28. The patient was not considered a surgical candidate for his mild OSA; therefore, watchful waiting and re-initiation of montelukast proceeded with initiation of oral iron. At sleep clinic follow up, family noted improvement of hallucinations for 2-3 months and then restart, with worsening. Upon medication review, Montelukast was the inciting factor to the presence and resolution of hallucinations.

Conclusion

In this patient the montelukast seemed to be the triggering factor of AIWS. It has been suggested that the inhibition of leukotriene receptors in the brain could be responsible for this drug reaction. No other obvious triggers, or results of work up were able to better explain his resolution once he discontinued montelukast. This just further promotes close pharmacologic vigilance in the pediatric population.

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1033 The link between vision loss and sleep
Authors: Safarpour Yasaman , Taweesedt Pahnwat , Gill Kirat
Published: May 2023

Introduction

Non-arteritic ischemic optic neuropathy (NAION) is the most common optic nerve disorder among patients over the age of 50. Several risk factors have been associated with NAION including systemic hypertension, diabetes mellitus, advanced age, and certain optic disc morphologies. A significant association between obstructive sleep apnea (OSA) and NAION has also been reported. Here, we present a case of a middle-aged man with a recent diagnosis of NAION who was subsequently found to have OSA.

Report of case(s)

A 53-year-old man with a remote history of head injury with concussion and tobacco use was referred to the Sleep Medicine Clinic from Ophthalmology for evaluation of obstructive sleep apnea (OSA). The patient initially presented to Ophthalmology due to acute onset, painless, left-sided, inferior vision loss. The patient was otherwise healthy and denied a history of diabetes mellitus or hypertension. He did report alcohol and cigar use on the night prior to the acute onset vision loss. He denied fevers, chills, joint or jaw pain, scalp tenderness, or jaw claudication. On initial evaluation he was found to have significant left eye optic disc edema. Blood test revealed normal complete blood count (CBC), erythrocyte sedimentation rate (ESR), and C-Reactive protein (CRP). His orbit and brain magnetic resonance imaging with and without contrast revealed no significant findings. He was subsequently diagnosed with left NAION. Further review of symptoms was positive for snoring, dry mouth, nighttime awakenings, and unrefreshing sleep, concerning for OSA and leading to referral to our Sleep Medicine Clinic. During initial consultation in Sleep Medicine, he denied symptoms concerning for any other sleep disorders. He subsequently underwent a home sleep test (WatchPAT) which confirmed the diagnosis of OSA. The apnea-hypopnea index (AHI) was 7.9 and the lowest oxygen saturation was 88%.

Conclusion

Given the reported association between NAION and OSA, a careful history should be obtained to screen for OSA when NAION is diagnosed.

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1037 Central sleep apnea due to high altitude periodic breathing
Authors: Srivali Narat , Tobias Lauren
Published: May 2023

Introduction

Many popular tourist destinations are at high-altitude. Visitors commonly report poor sleep quality during the first few nights after arriving, but some do not resolve over time and daytime symptoms may develop that require medical attention.

Report of case(s)

A previously healthy 76-year-old American man presented with progressive fatigue and frequent nocturnal awakenings to a clinic in Bogota, Columbia (altitude 2640 meters), where he had been living for eighteen months during the COVID-19 pandemic lockdown due to limited ability to travel. An arterial blood gas on room air revealed hypocapnia with a partial pressure of CO2 of 25 mmHg. A polysomnography (PSG) performed in Bogota demonstrated an apnea-hypopnea index (AHI) of 98 events/hour consisting of predominately central as well as obstructive respiratory disturbances (Figure 1). After a titration study, he was placed on treatment with continuous positive airway pressure (CPAP) at 10 cmH2O along with oxygen 1 L/min, but he had difficulty acclimating to treatment. The patient presented to our institution two months after returning to the USA with significantly improved symptoms despite remaining off CPAP. Repeat PSG revealed a substantial reduction in the AHI at 15 events/hour consisting of only central respiratory disturbances in the supine position during transitional N1/N2 sleep (Figure 2). Positional therapy was recommended. A repeat home sleep study performed three months later to reassess disease severity during non-supine sleep showed resolution of respiratory disturbances (Figure 3). High-altitude periodic breathing is a common phenomenon, characterized by alternating periods of absent respiratory efforts with periods of hyperventilation without another etiology (1, 2). It occurs due to the interaction of hypocapnia and increased loop-gain (2). Central sleep apnea (CSA) is considered a disorder only when associated with symptoms, not simply due to an elevated central apnea index (3). The more rapid ascent and the higher the altitude, the greater risk of developing periodic breathing. Descending to a lower altitude will often resolve apnea after few days but the phenomenon can persist for up to months (2, 4) as our patient.

Conclusion

CSA develops commonly upon ascent to high altitude. When feasible, symptomatic patients should be encouraged to descend to a lower altitude.

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1039 The Progression of Sleep-Related Breathing Disorders in a Patient with Joubert syndrome
Authors: Taweesedt Pahnwat , Safarpour Yasaman , Okorie Caroline
Published: May 2023

Introduction

Joubert syndrome (JS) is a rare autosomal recessive disease characterized by malformations of the cerebellar vermis, hypotonia, developmental delay, and respiratory variability. Among the potential health challenges that children with congenital malformations of the central nervous system including JS, may face, sleep concerns are frequent and may include sleep-related breathing disorders (SRBDs).

Report of case(s)

A 17-month-old female with JS was referred to the pediatric pulmonary clinic due to disrupted and fragmented sleep. She had frequent nocturnal awakenings, snoring, mouth breathing, and witnessed apneas. There was no family history of SRBDs. Physical exam was notable for high-arched palate, diffuse hypotonia, and intermittent periods of tachypnea followed by apneas, even when awake. Her polysomnography (PSG) demonstrated an apnea-hypopnea index (AHI) of 27.1/hour, with the obstructive apnea-hypopnea index (oAHI) of 18/hr with central apnea index (CAI) of 9.1/hr and nadir oxygen saturation (SpO2) of 87%. An attempt was made to initiate supplemental oxygen; however, the patient did not tolerate the cannula. At that time, neither adenoid nor tonsillar hypertrophy were noted and surgical intervention was not indicated. The repeat PSG one year later demonstrated AHI of 9.1/hour, oAHI of 4.7/hr with CAI of 4.4/hr and nadir SpO2 of 84%. At this time, she did demonstrate enlarged adenoids and tonsils and underwent adenotonsillectomy with some clinical improvement in snoring. Her mother noted continued pauses in breathing and post operative PSG demonstrated AHI of 12.8/hour, oAHI of 1.4/hr and CAI of 11.4/hr and nadir SpO2 of 79%. The patient had demonstrated worsening episodic tachypnea and central apneas and the decision was made to attempt initiation of a respiratory assist device to regulate breathing and ventilation. Due to the patient’s age, intensive therapy desensitization is required to allow her to tolerate positive airway pressure therapy.

Conclusion

Patients with JS are at high risk for complex SRBDs as part of their clinical presentation. It is therefore important to carefully monitor the character of sleep-disordered breathing, offering appropriate treatments where indicated. It is important to note the added challenges of young pediatric patients who often require deliberate desensitization interventions to proceed with successful treatment.

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1040 Sleep Hypoventilation with Daytime Eucapnia in COPD May Predict Hypercapnia During Exacerbation
Authors: Tejwani Dimple , Lobrutto Kelly , Naik Sreelatha
Published: May 2023

Introduction

Patients with severe Chronic Obstructive Pulmonary Disease (COPD) are known to be at risk for nocturnal hypoventilation1. We present a case of patient with severe COPD with near normalization of PaCO2 levels after exacerbation but persistent nocturnal hypoventilation.

Report of case(s)

71-year-old woman with COPD Group 4D, on home oxygen, was seen in pulmonary clinic after two hospitalizations for hypercapnic respiratory failure, PcO2 >100 mm Hg requiring acute Noninvasive ventilation (NIV) support. Three weeks after discharge, ABG improved to 7.39/49/140 on 32% Fio2, preventing her from qualifying for long-term home NIV. Sleep study was negative for sleep apnea but showed hypoventilation during sleep. Wake supine transcutaneous CO2 was 45-47 mmHg, increasing to 51-55 mmHg during sleep, worse with supplemental oxygen to 66-67 mm.

Conclusion

Chronic hypercapnia is a poor prognostic indicator in COPD4. In patients with persistent hypercapnia following COPD exacerbation, NIV prolongs time to re-admission or death within 12 months2. Blunting of chemoreceptor response has been noted in hypercapnic patients3, possibly causing subsequent daytime hypercapnia and overt respiratory failure. However, nocturnal hypercapnia is present in some patients and may be a risk factor for profound, life-threatening hypercapnia during exacerbation. Future studies are needed to better phenotype patients such as ours who may be seemingly eucapnic in between exacerbations, but markedly hypercapnic during exacerbation, to determine if there is benefit in treating these patients with NIV as well.

Support (if any)

1. The American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Report of American Academy of Sleep Medicine Task Force. Sleep 1999:22:667-689 2. Murphy PB, Rehal S, Arbane G, Bourke S, Calverley PMA, Crook AM, et al. Effect of home noninvasive ventilation with oxygen therapy vs oxygen therapy alone on hospital readmission or death after an acute COPD exacerbation: a randomized clinical trial. JAMA. 2017:317:2177 3. Scano G,Spinelli A, Duranti R, et al. Carbon dioxide responsiveness in COPD patients with and without chronic hypercapnia. Eur Respir J 1995:8:78-85 4. Cooper CB, Waterhouse J, Howard P. Twelve-year clinical study of patients with hypoxic co pulmonale given long term domiciliary oxygen therapy. Thorax 1987:42:105-110
1043 A Rare Case of Non-24-hour Sleep-Wake Rhythm Disorder in A Sighted Patient
Authors: Tu Xinhang , Peng Victor , So Jennifer
Published: May 2023

Introduction

Non-24-hour sleep-wake disorder is a circadian rhythm sleep disorder which causes failure of endogenous circadian rhythm cycles to synchronize to a 24-hour day. Despite an unknown prevalence in sighted people, it's thought to be rare. We present a case of a sighted patient with concurrent bipolar disorder who presented with excessive sleepiness since preadolescence, and was later found to have N24SWD.

Report of case(s)

A 29 year old woman with bipolar disorder presented with excessive daytime sleepiness and irregular sleep schedule since age 12. During her teenage years she often fell asleep at school, and she felt the sleepiness could be associated with psychotropic medication. As she grew up, despite her bipolar disorder was well-controlled, the daytime sleepiness persisted, which caused great challenge concentrating at work and difficulty holding a job. She denies cataplexy, hypnagogic hallucinations, sleep paralysis, or restless legs syndrome symptoms. She had no history of shift work or abnormal movements during sleep. Her bedtime advanced and cycled through a 24-hour period according to sleep diary. Her rise time maintains a consistent interval with her bedtime. Previously she had multiple sleep latency test and polysomnogram, after which she was diagnosed with idiopathic hypersomnia. She was treated with several stimulants without much improvement. She was offered CBT-I but hasn’t gone. She failed trial of a standardized schedule and found it stressful. She tried melatonin and light therapy for a short time without much of success, she was subsequently started on tasimelteon and the clinical response is to be followed.

Conclusion

N24SWD is reportedly rare in the sighted population, with a possible different mechanism from that of the blind population. Behavioral and environmental factors might contribute to the dysynchrony between a normal central circadian pacemaker and a non-24-hour sleep-wake behavioral pattern. Our patient's sleepiness persisted despite her psychiatric disorders were in remission. Altered circadian rhythms are not uncommon in patients with psychiatric disorders, and circadian rhythm dysfunction may be a trait marker of bipolar disease. Some antidepressant are also found to cause potential iatrogenic circadian rhythm sleep disorders. Psychosocial interventions that target stabilizing daily rhythms in patients with concurrent psychiatric illness can be helpful.

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1044 Spinal Muscular Atrophy and Sleep: Double-Trouble
Authors: Willis Aaron , Jefferson Larry , Revana Amee
Published: May 2023

Introduction

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder which leads to progressive muscular weakness and respiratory impairment. Affected patients experience a variety of sleep problems including obstructive sleep apnea, nocturnal hypoventilation, and increased sleep disturbances. As of 2019, the first gene therapy was approved to treat patients with SMA under the age of 2, onasemnogene abeparvovec-xioi (ZolgensmaTM), with expedited approval due to findings of improved motor function and milestone achievement as well as survivability. We describe an unusual case of twins with SMA whom developed worsening obstructive sleep apnea after gene therapy.

Report of case(s)

The patients are a set of 3-year-old male twins with past medical history significant for premature lung disease related to extreme prematurity at 24-weeks and SMA type 2. They were initially referred for polysomnography (PSG) at 1 year of age for evaluation of snoring and as a precaution related to their underlying diagnosis. Physical examination findings were significant for tongue atrophy with fasciculations and generalized muscular weakness which spared the face. Neither twin achieved gross motor milestones of standing or walking to that point. Both patients would receive the gene therapy infusion at 1 year, 8 months with subsequent improvement in hypotonia and ability to ambulate independently. For twin A, baseline PSG at age 1 showed mild obstructive sleep apnea (apnea-hypopnea index (AHI)= 3.24 events per hour) without any signs of hypoxemia or hypoventilation. By comparison, the patient’s post-gene therapy PSG (around 1.5 years post-infusion) at age 3, showed progression to moderate obstruction (obstructive AHI of 6.03 events per hour). For twin B, baseline PSG showed moderate obstructive sleep apnea (AHI=9.09 events per hour) which progressed into the severe range (AHI= 11.90 events per hour) over the same time course.

Conclusion

Sleep-disordered breathing in SMA is a commonly diagnosed entity. While airway obstruction related to hypotonia would be an expected contributor, our case suggests that despite recovery of motor function through use of gene therapy, clinicians should maintain a high level of suspicion for sleep problems with strong consideration for PSG due to the risk of sub-clinical progression of sleep obstruction.

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1045 Resolution of Sexsomnia with Positive Airway Pressure
Authors: Wu Chen , Sajid Mehwish
Published: May 2023

Introduction

Sexsomnia is an infrequently encountered non-rapid eye movement (NREM) arousal disorder that can overlap with obstructive sleep apnea (OSA). Treatment of underlying OSA has been reported to resolve sexsomnia episodes.

Report of case(s)

A 26-year-old overweight man was referred to our Sleep Disorders Center for evaluation of possible “REM sleep behavior disorder.” The patient’s wife reported that he would fondle her breasts while he slept. Episodes began 6 months prior to his referral and occurred once every 1-2 months. During episodes, the patient did not get out of bed. He did not recall the events and denied dream recall. The patient had an infant at home with resultant sleep deprivation. He slept between 5-7 hours a night and stated episodes were more common with decreased total sleep time. Additionally, he reported recent increase in stressors after moving in with his in-laws. On evaluation, patient endorsed bruxism for which he wore a mouth guard. He reported history of sleepwalking in elementary school. He denied excessive daytime sleepiness, snoring, witnessed apneas, gasping arousals, morning headaches, unrefreshing sleep, insomnia, or substance use. He was advised to increase total sleep time and pursue a baseline polysomnogram to evaluate for sleep-disordered breathing. The polysomnogram demonstrated moderate OSA (apnea/hypopnea index of 17). Excessive arousals out of N3 sleep were not reported. He was initiated on auto-titrating positive airway pressure (APAP) and maintained moderate adherence for 2 months. At his follow-up visit, he reported no further episodes of nocturnal fondling after PAP initiation despite persistent sleep deprivation and home stressors.

Conclusion

This case highlights the importance of screening for sleep-disordered breathing which can coexist with NREM parasomnias such as sexsomnia. Even in patients without clear symptoms of sleep-disordered breathing, the evaluation, diagnosis, and treatment of possible OSA could decrease the frequency of sexsomnia episodes. Although this case study was mainly limited by short follow-up duration, the patient’s resolution of sexsomnia in that time demonstrates the importance of treatment of concurrent sleep-related breathing disorders.

Support (if any)

None.
A fish for Phoebe: a new actinopterygian from the Upper Carboniferous Coal Measures of Saddleworth, Greater Manchester, UK, and a revision of Kansasiella eatoni
Authors: Caron Abigail , Venkataraman Vishruth , Tietjen Kristen , Coates Michael
Published: May 2023

The origin of crown Actinopterygii has been dated to near the Devonian-Carboniferous boundary, but poor phylogenetic signal occludes the origin of modern actinopterygian biodiversity. Scarcity of comparative endoskeletal anatomy from this period likely contributes to the uncertainty. For example, only a handful of neurocrania have been described from the Carboniferous period despite an abundance of fossil taxa. Here we present a new actinopterygian, Phoebeannaia mossae gen. et sp. nov., from the Bashkirian Coal Measures of Saddleworth, Greater Manchester, UK, represented by an exceptionally preserved neurocranium and associated dermal bones. Morphological similarities to the Virgilian Kansasiella eatoni prompted comparative study and construction of a new neurocranial character matrix. Subsequent systematic analysis enabled identification of a cluster of similar Late Palaeozoic neurocrania, exploration of trends in braincase evolution across time, and investigation of potential causes of cladistic instability. Our neurocranial dataset reliably places this new specimen on the neopterygian stem near Kansasiella, but it struggles to incorporate extant taxa such as Polypteriformes, leading to uncertainty in branching pattern and inferred neurocranial transformation series. This work triples the number of complete Carboniferous neurocrania described with modern microcomputed tomography and provides a framework for future testing of large-scale hypotheses regarding the diversification and origin of ray-finned fishes.
Three-dimensional Reconstruction and Comparison of Temporomandibular Joint Space Volume Before and After Orthognathic Surgery in Patients with Skeletal Class III Malocclusion With Mandibular Deviation
Authors: Shi Hongli , Sun Xiumei , Xiao Yanju , Li Nannan , Wang Lin , Wu Guomin
Published: May 2023

Objective:

To look into the association between the degree of deviation and the changing trend in the temporomandibular joint (TMJ) space volume after orthognathic surgery in patients with skeletal Class III malocclusion.

Methods:

Twenty patients having combined orthodontic-orthognathic treatment for skeletal Class III malocclusions with mandibular deviation were chosen, and craniofacial spiral CT was performed before (T0), two weeks after (T1), and six months after (T2) surgery. Using 3D volume reconstruction, further partitioning, and analysis of each domain’s volume changes over time, the TMJ space volume is to be obtained. The differences in changes between groups A (mild deviation group) and B (severe deviation group) were examined to examine the impact of the degree of deviation on the TMJ space volume.

Results:

A statistically significant difference (P<0.05) existed between the postoperative TMJ space volume in group A and the preoperative overall, anterolateral, and anteroinferior space volume; the same difference also existed between the postoperative TMJ space volume in the NDS and the preoperative posterolateral, posteroinferior space volume. In group B, the postoperative TMJ space volume was statistically significant (P<0.05) compared with the preoperative total and anteroinferior space volume in the DS; the difference between the total volume of the T1 stage on the NDS and the total volume of the T0 stage was statistically significant (P<0.05). The two groups showed substantial differences in the space volume changes between the T1-T0 phase and the T2-T1 period.

Conclusion:

Patients with skeletal Class III malocclusion and mandibular deviation after orthognathic surgery see a change in the TMJ space volume. All patient types experience a largely consistent space volume change trend two weeks after surgery, and the degree of mandibular deviation is correlated with the intensity and longevity of the alteration.
Efficacy of Nostril Supportive Splint Treatment for Nasal Septum Deformities after Le Fort I Osteotomy
Authors: Moroi Akinori , Takayama Akihiro , Gomi Karen , Ono Sumire , Yoshizawa Kunio , Ueki Koichiro
Published: May 2023

This retrospective study aimed to evaluate the efficacy of support splint treatment for deformities and deviations of the nasal septum after Le Fort I osteotomy (LFI). Patients were divided into two groups: the retainer group wore a nasal support splint immediately after LFI for 7 days, and the no retainer group did not wear a nasal support splint. Evaluation was performed by measuring the ratio of the difference between the left and right sides of the nasal cavity area (ratio of nasal cavity) and the angle of the nasal septum using three computed tomography frontal images (anterior, middle, and posterior) before and one year postoperatively. Sixty patients were included and divided into two groups, the retainer and no retainer group (n=30 each). Regarding the ratio of nasal cavity on middle images at one year postoperatively, the retainer and no retainer groups differed significantly (0.79±0.13 and 0.67±0.24, respectively; P=0.012). The angle of the nasal septum on anterior images at one year postoperatively was 164.8±11.7° in the retainer group and 156.9±13.5° in the no retainer group, showing a significant difference (P=0.019). This study suggests that support splint treatment after LFI is effective in preventing post-LFI nasal septal deformation or deviation.
Evaluating the Effectiveness of Potential Interventions for Guinea Worm Disease in Dogs in Chad Using Simulations
Authors: Wang Yifan , Perini Tyler , Keskinocak Pinar , Smalley Hannah , Swann Julie , Weiss Adam
Published: May 2023

Guinea worm disease (or dracunculiasis) is currently transmitted among dogs in Chad, which presents risks for the human population. We studied how interventions implemented at different levels might reduce the spread of Guinea worm disease (geographically and over time) and what levels of interventions might accelerate elimination. We built a multi-water-source agent-based simulation model to analyze the disease transmission among dogs in Chad, as well as in geographic district clusters, and validated it using local infection data. We considered two interventions: (i) tethering, where infected dogs are kept on a leash during periods of infectivity, and (ii) Abate®, under which the water source is treated to reduce infectivity. Our results showed that elimination (0 dog infections) is most likely achieved within five years with extremely high levels of tethering (95%) and Abate (90%), when intervention levels are uniform across district clusters. We used an optimization model to determine an improved strategy, with intervention levels which minimize the number of dogs newly infected in the sixth year, under limitations on intervention levels across clusters; the number of dogs infected after five years of intervention could be reduced by approximately 220 dogs with an optimized strategy. Finally, we presented strategies that consider fairness based on intervention resource levels and outcomes. Increased tethering and Abate resources above historical levels are needed to achieve the target of Guinea worm disease elimination; optimization methods can inform how best to target limited resources and reach elimination faster.
Relationship between branched chain amino acids and type 2 diabetes: a bidirectional Mendelian Randomization study
Authors: Mosley Jonathan D. , Shi Mingjian , Agamasu David , Vaitinadin Nataraja Sarma , Murthy Venkatesh , Shah Ravi V. , Bagheri Minoo , Ferguson Jane F.
Published: May 2023

Background

Human genetic studies suggest that the branched chain amino acids (BCAA) valine, leucine and isoleucine have a causal association with type 2 diabetes. However, inferences are based on analyses of a limited number of genetic loci associated with BCAAs. Whether these conclusions are supported when using instrumental variables for BCAAs that capture a broad set of genetic mechanisms is not known.

Methods

We constructed and validated instrumental variables for each BCAA using large well-powered datasets and tested their association with type 2 diabetes using the two-sample inverse variance weighted (IWV) Mendelian randomization (MR) approach. Sensitivity analyses were performed to ensure the accuracy of the findings. Instrumental variables for type 2 diabetes, fasting insulin and body mass index (BMI) were also tested for associations with BCAA levels.

Results

There were no significant associations with diabetes for valine (beta=0.17 change in log-odds per standard deviation change in valine, [95% CI, −0.28 - 0.62], p=0.45), leucine (beta=0.19 [−0.30 - 0.68] p=0.45) or isoleucine (beta=0.02 [−0.54 - 0.59], p=0.94). In contrast, type 2 diabetes was associated with each BCAA (valine: beta=0.08 per standard deviation change in levels per log-odds change in type 2 diabetes, [0.05 - 0.10], p=1.8×10−9), (leucine: beta= 0.06 [0.04 - 0.09], p=4.5×10−8) and isoleucine (beta= 0.06 [0.04 - 0.08], p=2.8×10−8). The type 2 diabetes associations were replicated in an independent population, but not in a second population where type 2 diabetes cases were removed, highlighting the consistency and specificity of the association. Similar positive associations were seen for fasting insulin and BMI with the BCAAs. In multivariable MR analyses, type 2 diabetes and fasting insulin had consistent independent associations with each BCAA.

Conclusions

These data suggest that the BCAAs are not mediators of type 2 diabetes risk but are biomarkers of diabetes and higher insulin.
Exploring the common genetic architecture of autism spectrum disorder using a novel multi-polygenic risk score approach
Authors: Schmilovich Zoe , Bourque Vincent-Raphaël , Huguet Guillaume , He Qin , Ross Jay P. , Jean-Louis Martineau , Saci Zohra , Chaumette Boris , Dion Patrick A. , Jacquemont Sébastien , Rouleau Guy A.
Published: May 2023

Compared to disorders of similar heritability and contribution of common variants, few genome-wide significant loci have been implicated in autism spectrum disorder (ASD). This undermines the use of polygenic risk scores (PRSs) to investigate the common genetic architecture of ASD. Deconstructing PRS-ASD into its related traits via “developmental deconstruction” could reveal the underlying genetic liabilities of ASD. Using the data of >24k individuals with ASD and >28k of their unaffected family members from the SSC, SPARK, and MSSNG cohorts, we computed the PRSs for ASD and 11 genetically-related traits. We applied an unsupervised learning approach to the ASD-related PRSs to derive “multi-PRSs” that captured their variability in orthogonal dimensions. We found that multi-PRSs captured a similar proportion of genetic risk for ASD in cases versus intrafamilial controls (ORmulti-PRS=1.10, R2=0.501%), compared to PRS-ASD itself (ORPRS-ASD=1.16, R2=0.619%). While multi-PRS dimensions conferred risk for ASD, they had “mirroring” effects on developmental phenotypes among cases with ASD. We posit that this phenomenon may partially account for the paucity of genome-wide significant loci and the clinical heterogeneity of ASD. This approach can serve as a proxy for PRS-ASD in cases where non-overlapping and well-powered GWAS summary statistics are difficult to obtain, or accounting for heterogeneity in a single dimension is preferable. This approach may also capture the overall liability for a condition (i.e.: genetic “P-factor”). Altogether, we present a novel approach to studying the role of inherited, additive, and non-specific genetic risk factors in ASD.
Complex patterns of multimorbidity associated with severe COVID-19 and Long COVID
Authors: Pietzner Maik , Denaxas Spiros , Yasmeen Summaira , Ulmer Maria A. , Nakanishi Tomoko , Arnold Matthias , Kastenmüller Gabi , Hemingway Harry , Langenberg Claudia
Published: May 2023

Early evidence that patients with (multiple) pre-existing diseases are at highest risk for severe COVID-19 has been instrumental in the pandemic to allocate critical care resources and later vaccination schemes. However, systematic studies exploring the breadth of medical diagnoses, including common, but non-fatal diseases are scarce, but may help to understand severe COVID-19 among patients at supposedly low risk. Here, we systematically harmonized >12 million primary care and hospitalisation health records from ∼500,000 UK Biobank participants into 1448 collated disease terms to systematically identify diseases predisposing to severe COVID-19 (requiring hospitalisation or death) and its post-acute sequalae, Long COVID. We identified a total of 679 diseases associated with an increased risk for severe COVID-19 (n=672) and/or Long COVID (n=72) that spanned almost all clinical specialties and were strongly enriched in clusters of cardio-respiratory and endocrine-renal diseases. For 57 diseases, we established consistent evidence to predispose to severe COVID-19 based on survival and genetic susceptibility analyses. This included a possible role of symptoms of malaise and fatigue as a so far largely overlooked risk factor for severe COVID-19. We finally observed partially opposing risk estimates at known risk loci for severe COVID-19 for etiologically related diseases, such as post-inflammatory pulmonary fibrosis (e.g.,MUC5B,NPNT, andPSMD3) or rheumatoid arthritis (e.g.,TYK2), possibly indicating a segregation of disease mechanisms. Our results provide a unique reference that demonstrates how 1) complex co-occurrence of multiple – including non-fatal – conditions predispose to increased COVID-19 severity and 2) how incorporating the whole breadth of medical diagnosis can guide the interpretation of genetic risk loci.
Association of age at menarche and menopause, reproductive lifespan, and stroke among Chinese women: Results from a national cohort study
Authors: Chen Lu , Hu Zhen , Wang Xin , Zheng Congyi , Cao Xue , Cai Jiayin , Tian Yixin , Gu Runqing , Zhang Linfeng , Wang Zengwu
Published: May 2023

Background

The association between age of menarche, age of menopause, reproductive lifespan and risk of stroke in Chinese women remains unclear and requires further clarification.

Methods

A stratified multi-stage random sampling method was used to select participants at baseline in 2012-2015. The participants’ basic information was collected through a standardized questionnaire by professional investigator and examined by trained medical personnel. Follow-up was completed in 2019 to collect the stroke events. The Cox proportional hazards models were used to evaluate hazard ratios between reproductive factors and stroke risk.

Results

Overall, 11,256 women (5,155 non-menopausal women and 6,101 menopausal women) were included (mean [standard deviation] age, 55.2 [12.9] years). The risk was highest in women with menarche at age ≥17 years (HR, 1.290; 95%CI, 0.959∼1.733) and with reproductive lifespan ≤28 years (HR, 1.643; 95%CI, 1.041∼2.595). Age at menarche was positively associated with risk of stroke (HR, 1.086; 95%CI, 1.006∼1.172). There was a negative association between age at menopause and stroke risk in women with 2 live births (HR, 0.897; 95%CI, 0.834∼0.964). Reproductive lifespan was negatively associated with risk of stroke (HR, 0.963; 95%CI, 0.946∼1.027). Subgroup analysis also showed that association between age at menarche, reproductive lifespan and stroke events.

Conclusions

Chinese women with late age at menarche and shorter reproductive lifespan have higher risk of stroke according to a large prospective study.
Handgrip strength on the unaffected side associated with cardiorespiratory fitness in male patients with stroke
Authors: Chen Yuan , Zhou Mingchao , Zha Fubin , Zhang Shaohua , Luo Jiao , Huang Meiling , Yang Qiangqing , Shan Linlin , Wang Yulong
Published: May 2023

Objectives

To investigate factors related to cardiorespiratory fitness in patients with stroke and explore the association between handgrip strength (HS) and peak oxygen utilization (VO2peak).

METHODS

The present study adopted a cross-sectional method. Seventy male patients who had been clinically diagnosed with ischemic or hemorrhagic stroke were recruited for this study. HS on the unaffected side (uHS) was measured using a hydraulic hand dynamometer and adjusted for body mass index (uHSBMI) and body surface area (uHSBSA). Concurrently, the VO2peak was measured using a cardiopulmonary exercise test system. Univariate, multiple linear regression analyses were used to evaluate the association between various participant characteristics and the VO2peak.

RESULTS

The average age of the 70 selected male patients was 51.6 ± 10.3 years. The Barthel Index (BI), uHS, uHSBMI, and uHSBSAwere the independent predictors of VO2peak. The National Institutes of Health Stroke Scale (NIHSS), body mass index (BMI), and body surface area (BSA) were negatively correlated with the VO2peak. The estimation of VO2peak using linear regression, including age, BI, uHSBSA, and anaerobic threshold (AT) as independent variables, explained 65.5% of the variance in the VO2peak.

CONCLUSION

BMI- and BSA-adjusted uHS appear to be independent factors associated with cardiorespiratory fitness in male patients with stroke. The anaerobic threshold (AT) combined with uHSBMI/uHSBSAmay provide a more reliable assessment of the aerobic capacity post-stroke. The measurement of handgrip strength is a simple, risk-stratifying method that may help determine the cardiorespiratory fitness of patients with stroke, but a larger study with diverse subjects is needed.