Long-term improvement after combined immunomodulation in early post-H1N1 vaccination narcolepsy

Case report. In late 2009, a 2.5-year-old boy (child 1) was H1N1 vaccinated with H1N1 pandemic influenza vaccine (Pandemrix; GlaxoSmithKline, London, United Kingdom). He had a history of asthma/allergies and sleep talking/sleepwalking. Medio August 2013, he developed severe sleepiness, took 2–4 naps/day, and experienced episodes of sleep paralysis. We examined him primo September 2013 when the baseline Epworth Sleepiness Scale (ESS) score was 14/24 and multiple sleep latency test (MSLT) showed a mean sleep latency of 5 minutes with sleep onset REMs (SOREMs) in 4/4 nap opportunities. CSF hypocretin-1 levels were low (77 pg/mL; normal values $200 pg/mL). In late September 2013, cataplexy (tongue protrusion, facial muscles hypotonia, and head drop) triggered by laughter/emotional stress emerged and rapidly escalated to several partial/fulminant attacks/day. In the beginning of October 2013, having obtained informed consent, we initiated treatment of IVIg 1 g/kg/day for 2 consecutive days, followed by methylprednisolone 20 mg/kg/ day for 4 days, administered 3 times at monthly intervals (T1, T2, and T3). During T1, T2, and T3 methylprednisolone treatment days, cataplexy completely disappeared: he did activities such as watching cartoons and making jokes, without muscle weakness. However, cataplexy gradually reappeared 1–2 weeks after treatment. Likewise, the ESS score normalized from 14/24 to 3/24 during T1 methylprednisolone treatment, from 8/24 to 2/24 during T2 IVIg and methylprednisolone, and from 14–16/ 24 to 7/24 after T3. After T3, hypnagogic hallucinations emerged, but no microsleeps were reported; he took only 1 daily nap. The CSF hypocretin-1 levels had dropped to undetectable levels (,40 pg/mL). From October 2014 to January 2015, his status was 3–4 naps/day, cataplexy and hypnagogic hallucinations several times/week. Follow-up MSLT mean sleep latencies in January 2014 and June 2015 were normal (11.5 minutes and 12.5 minutes, respectively). In late March 2015, another, otherwise healthy, 6-year-old boy (child 2) developed 2–4 sleep attacks/day. His nocturnal sleep was disrupted by awakenings, nightmares, and dream enactment, and cataplexy (tongue protrusions and unsteady gait) became apparent in May 2015. Primo July 2015, the ESS score was 17/24, and he presented extensive spontaneous cataplexy, additionally exacerbated by joy/excitement. MSLT mean sleep latency was 2.1 minutes with SOREMs in 4/5 naps. CSF hypocretin-1 levels were ,40 pg/mL. A similar treatment regime as for child 1 was initiated. During T1 methylprednisolone treatment, the ESS score dropped transiently to 11/24, and the frequency of cataplexy decreased from 8 to 6 attacks/day. After T1, the ESS score returned to 16/24, and cataplexy gradually decreased to 3 attacks/day, remaining at that frequency until followup. Medio October, the follow-up ESS score was 16/24, and MSLT mean sleep latency was 6 minutes with SOREMs in 4/4 naps. He still had disrupted night sleep, and cataplexy had increased to 5–7 attacks/day. The CSF hypocretin-1 levels were unchanged (table).