Clinical Characteristics, Comorbidities, and Quality of Life in Korean Patients With Narcolepsy: Findings From an Online Survey

Study population

An online survey targeting members of the Korean Narcolepsy Patient Association (http://www.narcolepsy.kr) was conducted between July 29 and October 10, 2023. This association, a nonprofit organization founded in 2007, aims to enhance awareness of narcolepsy and advocates for the rights of patients. It actively offers educational programs and counseling services to its members. With approximately 500 active members, the association facilitates information sharing and mutual support through online communities and regular meetings. For this survey, individuals over the age of 18 who had been diagnosed with narcolepsy through polysomnography and the multiple sleep latency test at a medical institution were invited to participate.

Online survey

The Seoul National University ethics committee approved this study (IRB No. 2307-058-1447). Online informed consent was obtained from each participant. Participants were recruited through an online advertisement posted by the Korea Narcolepsy Association. Those who agreed to participate were provided with a Google Forms questionnaire. All methods adhered to relevant guidelines and regulations, including the Declaration of Helsinki. The survey was conducted anonymously using Google Forms, and no personally identifiable information was collected to protect patient privacy.

The survey included the following sections and questions; 1) basic information: sex, age, education level, job status, occupation, marital status, smoking habits, alcohol consumption, exercise frequency, and comorbid conditions. 2) Comorbid medical conditions: included hypertension, diabetes, heart disease, hyperlipidemia, kidney disease, pulmonary disease, stroke, epilepsy, depression, anxiety, bipolar disorder, schizophrenia, and others. Comorbid sleep disorders included obstructive sleep apnea, insomnia, restless legs syndrome (RLS), REM sleep behavior disorder, and others. Participants were asked to select all applicable conditions from a list of medical and sleep disorders. 3) Diagnosis of narcolepsy: age at diagnosis, type of narcolepsy, medical institution and department where the diagnosis was made, and the initial symptoms that led to the first consultation. Diagnostic tools for assessing narcolepsy included the Epworth Sleepiness Scale (ESS) [5], the Pittsburgh Sleep Quality Index (PSQI) [6], and the Ullanlinna Narcolepsy Scale [7]. The Ullanlinna Narcolepsy Scale consists of 11 items graded from 0 to 4 (never to daily/almost daily or >40 min to <10 min), covering the frequency of cataplexy (4 items), daytime napping (1 item), unintentional sleep lapses (5 items), and sleep latency (1 item), yielding a total score ranging from 0 to 44. 4) Treatment and medication: medication history, types of medications taken, and side effects experienced. 5) Quality of life: assessed using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) [8]. The WHOQOL-BREF is a highly efficient, cross-culturally valid, and psychometrically robust tool widely used for assessing quality of life in both clinical and research settings [9]. It is a 26-item questionnaire consisting of four domains: physical health, psychological health, social relationships, and environmental health. Quality of life scores range from 0 to 100, with a score above 60 indicating a good quality of life and a score below 40 indicating poor quality of life. 6) Perception and awareness: personal awareness of narcolepsy and experiences with delayed diagnosis.

Statistical analysis

Chi-square tests, Student’s t-tests, and Mann–Whitney U tests were used for statistical analysis. Multiple linear regression analyses were employed to identify factors associated with poor quality of life. Statistical significance was set at a two-tailed p value of less than 0.050. All statistical analyses were conducted using Python version 3.10.9 for Windows (https://www.python.org/downloads/release/python-3109/).

Demographic and clinical characteristics

In total, 299 individuals participated in the online survey. Table 1 presents the participants’ demographic and clinical characteristics. The mean age of participants was 32.2 years. The sample was composed of 59.9% women, 54.9% of whom were employed. Regarding education, 80% of participants were college graduates. Concerning marital status, 24.4% of the participants were married. Regarding lifestyle factors, 17.4% of the participants were current smokers, 70.6% were current drinkers, and 64.9% engaged in regular exercise. The first symptoms of narcolepsy appeared at a mean age of 16.6 years. The most common symptoms requiring medical attention were daytime somnolence, followed by cataplexy, hypnagogic hallucinations, sleep paralysis, and insomnia (Fig. 1). The ESS showed a mean score of 16.9, and the mean PSQI score was 9.6. The symptoms that prompted the first consultation included daytime somnolence (95%), cataplexy (37.1%), hypnagogic hallucinations (31.8%), sleep paralysis (25.4%), and insomnia (16.1%).

Table 1.

Demographics and characteristics of narcolepsy

Fig. 1.

Symptoms leading to the first consultation

Of the total participants, 184 (61.5%) were diagnosed with narcolepsy type 1 (NT1) and 115 (38.5%) with narcolepsy type 2 (NT2). The mean age at the onset of the first symptoms was 16.0 years for NT1 and 17.5 years for NT2, with no significant difference (p=0.087). Patients with NT1 had higher ESS (17.7 vs. 15.4, p=0.001) and PSQI scores (10.2 vs. 8.8, p=0.001). Daytime somnolence was reported by 93% of patients with NT1 and 98.3% of patients with NT2 (p=0.075). Hypnagogic hallucinations were more common in patients with NT1 (39.1% vs. 20.0%, p=0.001), as was sleep paralysis (31.0% vs. 16.5%, p=0.005). The insomnia rates were similar (16.8% in NT1 vs. 14.8% in NT2, p=0.851).

Comorbid conditions

Of the 299 respondents, 37 (12.4%) reported no comorbidities (Table 2). The most common comorbid conditions were depression (33.8%), obstructive sleep apnea (31.1%), anxiety disorder (22.4%), migraine (18.1%), and RLS (12.7%). Other notable conditions included hypertension (11.4%), hyperlipidemia (10.4%), insomnia (10.4%), diabetes mellitus (8.0%), REM sleep behavior disorder (7.0%), bipolar disorder (7.0%), ADHD (6.0%), and various other conditions (28.4%).

Table 2.

Comorbid conditions

Depression was more prevalent in patients with NT2 (41.7%) than in patients with NT1 (28.8%). Obstructive sleep apnea rates were similar between the groups. RLS and REM sleep behavior disorders were more common in patients with NT1. Among cardiovascular risk factors, diabetes mellitus and hyperlipidemia were significantly higher in the NT1 group than in the NT2 group.

Diagnostic delay

On average, the age at symptom onset was 16.6 years, and the age at diagnosis was 27 years, resulting in an approximately 11-year diagnostic delay (Table 3). Eighty-seven percent of participants perceived their narcolepsy diagnosis to be delayed. The leading cause of this delay was a lack of awareness about narcolepsy (74.6%). Additionally, 30.1% of patients were misdiagnosed with other diseases. Patients with NT2 were more likely to report non-severe initial symptoms as the cause of delay. Cost issues were rare in both groups.

Table 3.

Causes of diagnostic delay

Factors associated with quality of life

Patients with narcolepsy had an overall WHOQOL-BREF score of 42.1, indicating a moderately low quality of life (Table 4). Patients had a mean physical health score of 9.4, indicating significant physical health issues. The mean psychological health score was 10.5, indicating moderate psychological wellbeing. The social relationship score was 10.5, indicating average social support. The environmental health score was 11.7, indicating moderate satisfaction with living conditions.

Table 4.

WHOQOL-BREF score

When comparing the two groups, the WHOQOL-BREF showed similar physical (9.2 NT1 vs. 9.7 NT2, p=0.139) and psychological health scores (10.3 NT1 vs. 10.8 NT2, p=0.204). However, social relationship scores were lower in NT1 (9.9 vs. 11.4, p=0.005), as were environmental health scores (11.2 vs. 12.5, p=0.002). The total WHOQOL-BREF score was significantly lower in patients with NT1 (40.6 vs. 44.4, p=0.009). These differences remained significant even after controlling for age and sex, which differed between the groups. Therefore, patients with NT1 experienced more severe sleep disturbances and symptoms, with a lower quality of life in the social and environmental domains compared with that of NT2 patients.

A multiple linear regression analysis was conducted to examine the impact of various factors on the total WHOQOL score. The model explained approximately 29.6% of the variance in the total WHOQOL score (R²=0.296, adjust R²=0.254, F(17, 281)=6.953, p<0.001). Higher education levels were significantly positively associated with the WHOQOL total score (β=5.2188, standard error [SE]=1.632, t=3.198, p=0.002). Being married also showed a significant positive association (β=3.9739, SE=1.827, t=2.175, p=0.030), and regular exercise was positively correlated with the WHOQOL total score (β=3.9227, SE=1.722, t=2.279, p=0.023). Depression was negatively associated with the WHOQOL total score (β=-8.0709, SE=1.372, t=-5.881, p<0.001), as was age, though to a lesser extent (β= -0.1969, SE=0.098, t=-2.007, p=0.046). Both the ESS and the PSQI were significantly negatively associated with the WHOQOL total score (ESS: β=-0.4767, SE=0.178, t=-2.676, p=0.008; PSQI: β=-0.5026, SE=0.188, t=-2.676, p=0.008).

Clinical characteristics and comorbidities

The study cohort exhibited typical narcolepsy symptoms, with EDS being the most prevalent, followed by cataplexy, hypnagogic hallucinations, sleep paralysis, and insomnia. Patients with NT1 had higher ESS and PSQI scores, indicating more severe sleep disturbances compared with those of patients with NT2. Patients with NT1 were also more likely to experience hypnagogic hallucinations and sleep paralysis.

Comorbid conditions were common, with depression being the most frequently reported, followed by obstructive sleep apnea, anxiety disorder, migraine, and restless leg syndrome, which is in line with previous studies. Depression is a common comorbidity in patients with narcolepsy, with a significantly higher prevalence than in the general population. Patients with narcolepsy frequently report higher levels of depressive symptoms and a greater incidence of major depressive disorder [10-12]. Additionally, patients with narcolepsy have a higher risk of psychotic disorders and other psychiatric conditions [13,14]. Interestingly, depression is more prevalent in patients with NT2, whereas conditions, such as RLS and REM sleep behavior disorder, are more common in patients with NT1. Several studies have indicated that patients with NT2 are more likely to experience depressive symptoms than patients with NT1. This may be due to the absence of cataplexy in NT2, which often leads to diagnostic uncertainty and delays, potentially exacerbating psychological distress [13].

Approximately 13% of the participants reported having RLS, which was twice as common in NT1 than in NT2 in our study. A study by Plazzi et al. [15] showed that RLS was significantly more prevalent in patients with narcolepsy having cataplexy (14.7%) than in age-matched controls (3.0%). Periodic leg movements during sleep were common in RLS and also prevalent among patients with narcolepsy. Many patients with narcolepsy exhibit a high number of leg movements during sleep, although these movements are less periodic than those in patients with RLS [16]. RLS is particularly observed in patients with narcolepsy with cataplexy, suggesting a shared pathophysiology between the two conditions. Recognizing and addressing this comorbidity is crucial for effectively managing sleep disturbances and improving overall quality of life. Further studies are required to explore the underlying mechanisms and improve treatment strategies.

Diagnostic delays and misdiagnosis

A significant finding of this study was the substantial diagnostic delay experienced by patients with narcolepsy in Korea, averaging approximately 11 years from symptom onset to diagnosis. This delay is consistent with reports from other countries, where the average diagnostic delay ranges from 8 to 15 years, with some cases exceeding 60 years [2,3,17]. The primary factors contributing to this delay include a general lack of awareness of narcolepsy among the public and healthcare providers, as well as the overlap of narcolepsy symptoms with other neurological and psychiatric disorders [18].

In our study, lack of awareness was the most common reason for diagnostic delay, cited by 75% of the patients. Additionally, approximately 30% of the patients in this study were initially misdiagnosed with other conditions, complicating the path to correct diagnosis and appropriate treatment. Symptoms, such as EDS, are often misattributed to other conditions, such as depression, insomnia, or obstructive sleep apnea [18,19]. Therefore, our study suggests that raising public awareness and educating healthcare providers about narcolepsy should be promoted to prevent diagnostic delays in Korea.

Quality of life

The WHOQOL-BREF scores from this study indicated that patients with narcolepsy had significantly lower scores than the typical scores for the general population, suggesting that patients with narcolepsy experience considerably poorer quality of life across all domains. Patients with narcolepsy report low scores across all domains of the Short Form Quality of Life (SF-36 QoL) survey, particularly in physical role, vitality, and general health perception [20]. Narcoleptics score are significantly lower in all SF-36 domains than in the general population and even other chronic disease groups, such as multiple sclerosis, diabetes, and obstructive sleep apnea [21,22].

Our study showed that higher education levels, being married, and regular exercise were positively associated with better WHOQOL-BREF assessment scores, whereas depression, older age, and poor sleep quality were negatively associated. It is known that factors, such as EDS, employment status, and living with a partner significantly influence health-related quality of life. Symptoms, including EDS, cataplexy, sleep paralysis, and hallucinations, have a profound impact on physical, mental, and social health [23]. Mood symptoms and disease duration are significant predictors of role physical, vitality, social functioning, and role emotional functioning in patients with narcolepsy [22,24,25].

Patients with NT1 reported lower overall quality of life scores than those of patients with NT2, especially in terms of social relationships and environmental health. Cho et al. [26] also found poorer quality of life in NT1 than in NT2. Patients with NT1 scored significantly lower in the domains of mental health, vitality, and pain than patients with NT2 in their study.

Limitations

Although this study provided valuable insights, it had some limitations. The data were collected through an online survey, which may introduce self-selection bias, as it relies on self-reported information from patients who are members of the Korea Narcolepsy Patient Association. This method may exclude those who are less engaged in or aware of their condition. Although the number of participants in this study was relatively high and represents the largest sample to date, it comprised only 6.9% of the total estimated population of patients with narcolepsy in Korea, given the rare prevalence of the condition [4]. To more accurately represent the characteristics of Korean patients with narcolepsy, further studies involving a larger sample are needed. Finally, the cross-sectional nature of the survey did not allow for the establishment of causality.

Conclusion

This study underscores the significant impact of narcolepsy on quality of life and the critical need for increased awareness and education about the disorder among the public and healthcare providers in Korea. Substantial diagnostic delays and the prevalence of comorbid conditions call for a more proactive approach in recognizing and diagnosing narcolepsy. These findings highlight the critical areas for future research and policy development to support this underserved patient population.