LAUSR

Narcolepsy is a disorder of sleep characterized by pathologic daytime sleepiness classically divided into two major subtypes – those with or without cataplexy. The underlying pathophysiologic mechanism is thought to be related to hypocretin/orexin; pathologically low levels of hypocretin characterize narcolepsy with cataplexy. We present a complex case of weakness in a patient evaluated for narcolepsy. A 38 year-old male with a BMI of 33 presented with a decade of daytime sleepiness and sudden debilitating attacks of muscle weakness. He underwent level III home sleep testing revealing a respiratory event index of 5.3/h. After an unsuccessful trial of mandibular advancement, he was started on positive airways pressure (PAP) but continued to experience daytime sleepiness and episodes concerning for cataplexy including sensation of legs feeling stiff and falling with stress. He also described episodes of weakness while swimming with inability to stand or stabilize, prompting evaluation for narcolepsy with cataplexy. Sleep diary showed average nightly sleep of 6.5 hours, low sleep latency, and refreshing napping. He underwent PSG while using CPAP 8 cm H2O showing AHI 0.2/h, sleep time 6.2 hours, sleep latency 5.5 minutes and REM latency 33 minutes with evidence of REM sleep without atonia. He underwent MSLT showing a mean sleep latency of 7.6 minutes and 3/5 REM sleep onset periods. Therapeutic trials of venlafaxine and pitolisant did not result in symptomatic improvement, and further genetic testing with HLA DQB-1 was negative. CSF hypocretin measurement was normal (329 pg/mL, reference > 200 pg/mL). These effectively ruled out cataplexy as the cause of his weakness. He continued on PAP therapy, venlafaxine, and modafinil 200 mg for hypersomnia/narcolepsy without cataplexy with good response. We present a complex case highlighting the utility of HLA and confirmatory CSF testing in the evaluation of cataplexy with episodes of acute weakness accompanying stress and strong emotion, with particularly dangerous events during swimming. Due to lack of therapeutic response despite positive MSLT, further testing with HLA and CSF hypocretin were pursued. This case highlights the limitations of history alone in the diagnosis of cataplexy, and the utility of advanced testing.