Narcolepsy with co-occurring epilepsy: diagnostic pitfalls and management strategy

Narcolepsy and epilepsy are chronic neurological disorders that occasionally coexist. Overlapping symptoms, such as sudden loss of muscle tone and uncertainty regarding preservation of awareness, frequently complicate accurate diagnosis and ambiguity remains regarding optimal therapeutic strategies. To characterise the clinical features and treatment outcomes in individuals with comorbid narcolepsy and epilepsy, we described a 17-year-old girl with concomitant epilepsy and narcolepsy presented in our clinic. The overlapping symptomatology of narcolepsy and epilepsy can lead to significant diagnostic pitfalls, particularly when excessive daytime sleepiness is overlooked or attributed to external factors such as mental disorder or the side effects of antiseizure medications. Careful evaluation of clinical features, sleep studies and immunological markers through a multidisciplinary team approach is essential for accurate differentiation and optimal treatment. Prompted by this encounter, we additionally conducted a literature review and then synthesised ten reported cases of narcolepsy-epilepsy comorbidity, focusing on demographic profiles, diagnostic findings, treatment approaches and therapeutic outcomes. All ten published cases were diagnosed with narcolepsy type 1, predominantly with childhood or adolescent onset. EEG commonly showed 3-5 Hz generalised spike-and-wave discharges, and most individuals reported carrying the HLA-DQB1*06:02 allele. In more than 80% of cases, narcolepsy preceded or coincided with epilepsy, though diagnostic delays for narcolepsy were frequent. Both conditions generally responded well to combined standard treatments, such as pitolisant, sodium oxybate, lamotrigine and valproate, though antiseizure medications occasionally worsened sleepiness. This study underscores the diagnostic pitfalls associated to overlapping symptoms of narcolepsy and epilepsy and emphasises the value of multidisciplinary diagnostic collaboration for the timely recognition and effective management of these coexisting neurological disorders.