Reliability and validity of the Japanese version of the Ullanlinna Narcolepsy Scale and Swiss Narcolepsy Scale for screening Japanese individuals with narcolepsy type 1.

OBJECTIVE: To validate the Japanese versions of the Ullanlinna Narcolepsy Scale (J-UNS) and Swiss Narcolepsy Scale (J-SNS) for screening narcolepsy in the Japanese population and to discuss strategies for their use in hypersomniac individuals. METHODS: We selected 451 outpatients with excessive daytime sleepiness (EDS) already diagnosed according to the International Classification of Sleep Disorders third edition. They responded to both scales twice at 1-month intervals. After eliminating individuals who met the exclusion criteria, validity and reliability analyses were performed on 408 and 381 participants, respectively. RESULTS: Patients with narcolepsy type 1 (NT1) displayed higher J-UNS and lower J-SNS scores than those with NT2 and other sleep disorders. The intraclass correlation coefficients and weighted κ coefficient for scale scores in the total participants and patients with NT1 were ≥0.70 and ≥ 0.40, respectively, indicating high reliability. Furthermore, both the sensitivity and specificity of these scales upon using the original cut-off scores (14 for UNS and 0 for SNS) for detecting NT1 were 0.70 or ≥0.70, suggesting high validity. Additionally, the receiver operating characteristic curve analysis revealed that the best cut-off score did not change for the J-SNS but that for the J-UNS, it increased to 18. In our study, the scale's sensitivity and specificity changed from 96% to 82% and 58%-78%, respectively. CONCLUSIONS: Both scales revealed satisfactory screening abilities for NT1 in the Japanese population. However, it may be better to use J-UNS cut-off scores of 18 for a population with EDS.

Delayed sleep-wake phase disorder and its related sleep behaviors in the young generation.

Delayed sleep-wake phase disorder (DSWPD) is a sleep disorder in which the habitual sleep-wake timing is delayed, resulting in difficulty in falling asleep and waking up at the desired time. Patients with DSWPD frequently experience fatigue, impaired concentration, sleep deprivation during weekdays, and problems of absenteeism, which may be further complicated by depressive symptoms. DSWPD is typically prevalent during adolescence and young adulthood. Although there are no studies comparing internationally, the prevalence of DSWPD is estimated to be approximately 3% with little racial differences between Caucasians and Asians. The presence of this disorder is associated with various physiological, genetic and psychological as well as behavioral factors. Furthermore, social factors are also involved in the mechanism of DSWPD. Recently, delayed sleep phase and prolonged sleep duration in the young generation have been reported during the period of COVID-19 pandemic-related behavioral restrictions. This phenomenon raises a concern about the risk of a mismatch between their sleep-wake phase and social life that may lead to the development of DSWPD after the removal of these restrictions. Although the typical feature of DSWPD is a delay in circadian rhythms, individuals with DSWPD without having misalignment of objectively measured circadian rhythm markers account for approximately 40% of the cases, wherein the psychological and behavioral characteristics of young people, such as truancy and academic or social troubles, are largely involved in the mechanism of this disorder. Recent studies have shown that DSWPD is frequently comorbid with psychiatric disorders, particularly mood and neurodevelopmental disorders, both of which have a bidirectional association with the pathophysiology of DSWPD. Additionally, patients with DSWPD have a strong tendency toward neuroticism and anxiety, which may result in the aggravation of insomnia symptoms. Therefore, future studies should address the effectiveness of cognitive-behavioral approaches in addition to chronobiological approaches in the treatment of DSWPD.

Prevalence and Factors Associated With the Risk of Delayed Sleep-Wake Phase Disorder in Japanese Youth.

Background: Delayed sleep-wake phase disorder (DSWPD) is more prevalent among the younger generation. However, the prevalence of this disorder in Asia, particularly Japan, has not yet been elucidated. Furthermore, the impact of DSWPD morbidity on daytime functioning and factors associated with the presence of the disorder remain unclear. Methods: A web-based survey was conducted among youth aged 15-30 years. In total, 7,810 individuals completed the questionnaire. The questionnaire included items on sociodemographic variables as well as the Japanese version of the Biological Rhythms Interview of Assessment in Neuropsychiatry self-report (J-BRIAN-SR), which assesses the risk of DSWPD, sleep behaviors and possibly related lifestyle variables, productivity loss [WHO Health and Work Performance Questionnaire (HPQ)], and health-related quality of life (HRQOL). The risk of DSWPD was indicated by a J-BRIAN-SR score greater than or equal to 40 points and days of absence ≥4 days per month. After comparing these variables for participants at risk of DSWPD and those who were not, the factors associated with the risk of DSWPD were examined using logistic regression analysis, with sociodemographic and lifestyle variables as independent variables. Results: The overall prevalence of participants at risk DSWPDs was 4.3%. Compared with participants without DSWPD, those at risk of DSWPD presented significantly worse HPQ and HRQOL scores. The risk of DSWPD was positively associated with the presence of currently treated diseases, length of nighttime liquid crystal display (LCD) viewing, and being a high school/university students. It was negatively associated with habitual exercise. Conclusion: The risk of DSWPD seemed to be consistent with reports from Western countries, and individuals possibly affected by the disorder were thought to have deteriorated daytime functioning. In addition, lifestyle specific to youth, such as long-term LCD viewing at night and relatively loose social constraints, could be associated with the presence of DSWPD in this generation.

Changes in sleep behavior, sleep problems, and psychological distress/health-related quality of life of young Japanese individuals before and during the COVID-19 pandemic.

Social restrictions during the coronavirus disease (COVID-19) pandemic have impacted sleep behavior and sleep problems, and their related daytime functioning in young adults. However, no studies have examined such changes in young individuals from countries with mild infection intensity and social restrictions. Therefore, we focused on sleep behaviors and sleep issues in young people in Japan. This study was conducted before and after the pandemic (October 2019 and May 2020, respectively). In total, 2,222 (1,371 students and 851 workers) individuals participated and completed anonymous Web-based questionnaires concerning demographic characteristics, sleep behaviors, sleep problems using the Japanese version of the Epworth Sleepiness Scale (JESS) and the Athens Insomnia Scale (AIS-J), psychological distress using the Japanese version of the Kessler Psychological Distress Scale, and health-related quality of life (HRQoL) evaluated with the Short Form-8 (SF-8). A significantly delayed sleep phase was observed in the second survey compared to the first (p < .001) and was more pronounced in students than in workers (p < .001). The total sleep time, social jetlag degree, and JESS, AIS-J, and SF-8 scores were significantly improved after the pandemic (p < .001, p < .001, p < .001, p < .001, p < .05, and p < .001, respectively). Careful monitoring of whether these modest changes can lead to adjustment concerns is needed.

Leg movement activity during sleep in multiple sclerosis with and without restless legs syndrome.

STUDY OBJECTIVES: To carry out an analysis of leg movement activity during sleep in a polysomnography dataset of patients with multiple sclerosis (MS) in comparison to idiopathic restless legs syndrome (iRLS) and healthy controls. METHODS: In this cross-sectional, observational, instrumental study, 57 patients (males/females: 11/46; mean age 46.2 ± 10.2 years) with a diagnosis of MS underwent a telephone interview assessing the 5 standard diagnostic criteria for RLS and polysomnography. Sleep architecture and leg movement activity during sleep were subsequently compared: 1) 40 patients with MS without RLS (MS-RLS) vs 28 healthy controls; 2) 17 patients with MS with RLS (MS+RLS) vs 35 patients with iRLS; 3) MS+RLS vs MS-RLS. RESULTS: MS-RLS and MS+RLS presented increased sleep latency, percentage of sleep stage N1, and reduced total sleep time compared to healthy controls and iRLS, respectively. The periodic limb movements during sleep (PLMS) index was higher in MS-RLS than in healthy controls (P = .035) and lower in MS+RLS compared to iRLS (P = .024). PLMS in MS+RLS were less periodic, less often bilateral, and with shorter single movements compared to the typical PLMS in iRLS. CONCLUSIONS: MS is a risk factor for RLS, PLMS, and for a lower sleep quality in comparison to healthy patients. PLMS in MS+RLS are fewer and shorter if compared to iRLS. Our results suggest a dissociation between motor (PLMS) and sensory symptoms (RLS sensory component) in RLS secondary to MS, with possible treatment implications. CITATION: Ferri R, Sparasci D, Castelnovo A, et al. Leg movement activity during sleep in multiple sclerosis with and without restless legs syndrome. J Clin Sleep Med. 2022;18(1):11-20.

Restless legs syndrome and periodic limb movements in 86 patients with multiple sclerosis.

STUDY OBJECTIVES: To assess the frequency of restless legs syndrome (RLS), periodic limb movements during sleep (PLMS), and their overlap in a large sample of patients with multiple sclerosis (MS). To compare clinical and paraclinical findings among four subgroups of patients: RLS-/PLMS- (patients without RLS and PLMS), RLS+/PLMS- (patients with RLS and without PLMS), RLS-/PLMS (patients without RLS and with PLMS), and RLS+/PLMS+ (patients with both RLS and PLMS). METHODS: In this cross-sectional, observational, instrumental study, 86 patients (M/F: 27/59; mean age 48.0 ± 10.8 years) with a diagnosis of MS underwent a telephone interview assessing the five standard diagnostic criteria for RLS. Seventy-six participants underwent polysomnography (PSG) and maintenance of wakefulness test (MWT). Instrumental and clinical findings were subsequently statistically compared to investigate their association with RLS and PLMS index (PLMSI). RESULTS: RLS and PLMS (PLMSI ≥15/h) frequency in patients with MS were of 31.4% and 31.6%, respectively. Among patients with RLS, 37.5% had a PLMSI of at least 15/h. RLS-/PLMS+ group showed higher wake after sleep onset (p = 0.01), stage shifts per hour (p = 0.03), increased stage N1 (p = 0.03), and reduction in stage N3 (p = 0.01) compared to RLS-/PLMS-. RLS had no influence on clinical and PSG parameters (p = 0.45). CONCLUSIONS: RLS is highly frequent in patients with MS. The frequency of PLMS is comparable to the general population. The low percentage of patients with RLS having a high PLMSI, together with the absence of correlation between RLS and female gender and older age, supports the existence of a distinct symptomatic form of RLS in MS.

Framing multiple sclerosis under a polysomnographic perspective.

Multiple sclerosis (MS) is a mainly demyelinating, autoimmune, and disabling neurological disease. In addition to well-known clinically evident symptoms such as coordination or motor problems, increasing attention has been posed to a constellation of less evident symptoms significantly contributing to the clinical impact of MS. Among others, sleep symptoms have been only recently explored. This systematic review summarizes objective sleep findings detected by using polysomnography and their relationship with clinical variables in MS patients. While it is well known that sleep disorders are frequent in MS, objective clinical data are still scarce. Literature based on subjective reports indicate sleep disorders as highly frequent in MS patients; however, objective data are still scarce. New large case-control instrumental investigations are warranted to establish the real objective entity and impact of sleep comorbidities.

Rate of augmentation and risk factors with long-term follow-up in Japanese patients with restless legs syndrome.

OBJECTIVES: Preventing augmentation is the critical clinical issue for RLS treatment. As for augmentation in Asian RLS patients, there have been only four studies and the follow-up durations of these studies were not long. We investigated Japanese RLS patients with longer duration of treatment in a clinical setting. METHODS: This study is a retrospective assessment of 42 RLS patients with follow-up durations of longer than 18 months (78.4 ± 29.2, range 19-139) at two urban sleep centers in Osaka, Japan from May 2004 to April 2014. RESULTS: The mean age of first visit was 63.5 ± 14.1 years old and the estimated age of RLS onset was 47.9 ± 16.5 years old. Twenty-eight out of 42 patients were female. At initial evaluation, the mean International Restless Legs Scale score (IRLS score) was 22.0 ± 5.9. Thirty-one of 42 had already visited other clinics before coming to our sleep centers, and the number of clinics visited was 1.3 ± 0.6. Augmentation developed in two patients (4.8%), and the dosage of dopamine equivalent in patients with and without augmentation was 12.5 and 18.8 mg vs. 15.8 ± 17.7 mg. In the two RLS patients with augmentation, ferritin was 113.1 and 114.1 ng/mL, respectively, and the number of clinics before coming to our sleep centers was both three. CONCLUSIONS: The augmentation rate of Japanese RLS patients from our study is low compared with previous Western and Asian studies. It might be attributable to racial difference, lower dosage of dopaminergic treatment, and the level of ferritin.

Survey of the participants of EEG teaching courses provided by Japanese Society of Neurology: current state and gradual evolution for EEG teaching in the last 5 years.

We collected and analyzed the questionnaires from the participants in the annual EEG hands-on (5 times) and the regional EEG seminar (6 times). The board-certified neurologists among participants in the regional EEG seminar were always more than those in the annual EEG hands-on. Participants in the regional EEG seminar were more involved in EEGs than those in the annual EEG hands-on. The highly satisfactory lectures in the annual EEG hands-on were "normal EEG" and those in the regional EEG seminar were "EEG of epilepsy". The highly requested lectures in the annual EEG hands-on were "how to read EEG" and those in the regional EEG seminar were "EEG of epilepsy". By taking the needs of the participants into account, we only could provide more efficient teaching seminars to improve EEG reading skills of neurologists.

[Two cases of acute onset of focal cortical reflex myoclonus following acute aseptic meningoencephalitis with positive anti-glutamate receptor autoantibody].

Patient 1 was a 40-year-old man, who suffered from right leg myoclonus 1 week after an episode of fever and headache. Myoclonus disappeared 4 months after administration of clonazepam. Patient 2 was a 42-year-old man, who suffered from right leg myoclonus, attacks of speech arrest and a generalized tonic-clonic seizure. His symptoms disappeared after steroid-pulse therapy, but right leg myoclonus and episodic impairment of consciousness recurred within a month. He underwent another steroid-pulse therapy and his symptoms disappeared. In both patients, cerebrospinal fluid (CSF) study showed pleocytosis and elevated protein level, electrophysiological study showed cortical reflex by stimulation of the right tibial nerve, and brain MRI showed the high intensity area in the left parietal lobe. In addition, on electroencephalogram (EEG) spikes at vertex preceded myoclonic jerk of the right tibialis anterior muscle in both patients. These findings indicate that focal cortical reflex myoclonus was accompanied by acute central nervous system (CNS) infection. Furthermore, in both patients, autoantibody against glutamate receptor subunits ε2 was detected both in serum and CSF, which also suggest that autoimmune mechanism contributed in the pathophysiology of acute development of focal cortical reflex myoclonus.

Disseminated Nocardia farcinica infection in a patient with myasthenia gravis successfully treated by linezolid: a case report and literature review.

Nocardiosis is increasingly being diagnosed because of a growing population of immunocompromised hosts and improvements in the detection of Nocardia species in clinical laboratories. Historically, sulphonamides have been the first-line therapy for the treatment of nocardiosis, but sulphonamides tend to have a high rate of drug allergy in clinical settings. In this report, we described a disseminated Nocardia farcinica infection that occurred in a patient with myasthenia gravis who suffered from multiple drug allergies and was successfully treated using linezolid. We undertook a review of the literature of previously reported cases of nocardiosis treated with linezolid. To date, only 15 cases of nocardiosis treated with linezolid have been published. All cases exhibited long-term tolerance of linezolid, and 14 of 15 cases showed either an improvement in or complete clearance of the infection. According to the literature review, linezolid is an attractive alternative to trimethoprim-sulfamethoxazole for the treatment of disseminated nocardiosis, despite limited clinical evidence to support this claim.