Clinical and polysomnographic features in DQB1*0602 positive and negative narcolepsy patients: Results from the modafinil clinical trial

Background: Narcolepsy, a neurological disorder characterized by excessive daytime sleepiness and abnormal REM sleep, is known to be tightly associated with the human leukocyte antigen (HLA) DQB1*0602. Methods: In this study, baseline data collected for a large clinical trial involving 504 narcolepsy patients were used to compare clinical and polysomnographic features of narcolepsy patients with and without HLA-DQB1*0602. Comparisons were adjusted for possible confounding factors and linear regression modeling was used to extract the best predictors for DQB1*0602 positivity. Results: As previously reported, cataplexy was the best clinical predictor for DQB1*0602 positivity. At the polysomnographic level, subjects with DQB1*0602 were found to have a significantly more disrupted nocturnal sleep, a much shorter nocturnal rapid eye movement (REM) sleep latency and more multiple sleep latency test abnormalities (increased number of sleep onset REM periods and decreased mean sleep latency). We also found that subjects with DQB1*0602 had a much higher incidence of periodic limb movements during sleep, confirming the notion that this symptom is genuinely associated with the narcolepsy phenotype. Conclusions: These results support the notion that HLA-DQB1*0602-positive narcolepsy patients are more etiologically homogenous than HLA-DQB1*0602-negative narcoleptic patients.