テキサス大学（ダラス）教授、ハワード・ヒューズ医学研究所研究員として在米研究生活15年の柳沢正史さん。JSTの戦略研究（ERATO）「柳沢オーファン受容体プロジェクト」の総括責任者として、東京・お台場の日本科学未来館にも研究室を構え、日米間を往復する。5年目を迎える同プロジェクトの最新の研究成果を聞いた。

Even though we are currently in the midst of pandemic from coronavirus infection, the new influenza (H1N1) epidemic in 2009–2010 was unforgettable. Concurrently with the H1N1, narcolepsy surged in post–affected children in China. In Northern Europe, narcolepsy surged in children after H1N1 vaccination. Although there were many cases of H1N1 in Japan, there was no change in the incidence of narcolepsy because anti–influenza drugs prevented the disease from becoming more severe and the vaccine did not contain an adjuvant. It has recently become clear that the Spanish flu that prevailed about 100 years ago was also H1N1. Economo's encephalitis lethargica, which was prevalent at the same time, is thought to be autoimmune encephalitis rather than H1N1–induced influenza encephalitis. It has been reported that Economo's encephalitis caused damage to the hypothalamus, including the orexin system, resulting in lethargic symptoms.

Since the 2010s, the number of patients with neurodevelopmental disorders (ADHD, ASD) has been increasing among the patients who complain of hypersomnolence. Consideration of the course of symptoms revealed that the patient was originally below the threshold of the diagnostic criteria for neurodevelopmental disease, that hypersomnolence occurred from around adolescence, and that the case also met the criteria for neurodevelopmental disease. Although hypersomnolence was not noticeable in early childhood and inattention was the main symptom, the diagnostic criteria were not met. Hypersomnolence, on the other hand, increased from around adolescence, was added, and attention deficit was exacerbated. Therefore, it is considered that there are many cases that satisfy both the diagnosis of ADHD and central hypersomnia. ADHD characteristics such as attention deficit, hyperactivity, and poor impulsivity may be observed in children who have recovered from Economo's encephalitis and are called post–encephalitis behavioral disorders. The pathophysiology of Economo's encephalitis is presumed to be a disorder of the hypothalamus, including the orexin system, but it is possible that the disorder remained even after recovery.

We believe that impaired attention, and restlessness caused by the hypersomnolence in neurodevelopmental disorders can be explained by dysfunctions of the orexin system and its arousal system. H1N1 morbidity may trigger neurodevelopmental disorders accompanied by hypersomnolence.

要旨：症例は16 歳女性で，両側もやもや病の保存的加療中に過眠症発作を来した．過眠発作の形式と脳波所見は

  Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and frequent comorbid obesity. We present the safe perioperative management of a patient with narcolepsy who required mandibular surgery. A 22-year-old man (weight, 69.8 kg ; height, 160.8 cm ; BMI, 27.2) was scheduled to undergo a sagittal splitting ramus osteotomy. He was diagnosed as having narcolepsy at the age of 15 years, of having obstructive sleep apnea syndrome (OSAS) at the age of 20 years, and experienced drowsiness while driving at the age of 21 years (weight, 48 kg ; height, 156 cm ; BMI, 19.7) ; he was prescribed modafinil (200 mg) at this time. After taking his daily dose of modafinil (100 mg) on the morning of the surgery, general anesthesia was induced and maintained with air-oxygen-sevoflurane, remifentanil, and rocuronium to maintain his BIS value between 40 and 60. Following the osteotomy, his mandible was fixed using a 7-mm setback. After surgery, he emerged from anesthesia within 10 min at a BIS value of 92 and was extubated. His intraoperative course was uneventful, with no hemodynamic instability occurring. Postoperative hypertension required a reoperation for hemostasis with intravenous sedation under SpO₂ monitoring and capnography. Six months later, he was referred to a hospital for a reevaluation of his OSAS. His AHI (apnea hypopnea index) was exacerbated from 17.2/h to 26.0/h as a result of him being overweight (21.8 kg), rather than the downward position of the hyoid bone caused by the setback of the mandibular bone. BIS monitoring of the sevoflurane and remifentanil anesthesia during the surgery was useful for preventing postoperative oversedation in this narcoleptic patient. Modafinil is a central neurological stimulant (a non-amphetamine, wake-promoting compound used for excessive daytime sleepiness). Its reported side effects include postoperative hemodynamic instability. Further studies examining the perioperative risk when anesthetics and central neurological stimulants are combined in narcolepsy patients with OSAS are needed.