1008 Excessive daytime sleepiness in myotonic dystrophy treated with modafinil

Abstract

Abstract Introduction Physiology of excessive daytime sleepiness (EDS) in myotonic dystrophy type 1 (DM1) remains incompletely understood and best practice treatment approaches are unclear. Report of case(s) We present a 73-year-old man with atrial fibrillation, implantable cardioverter defibrillator for inducible ventricular tachycardia, hypertension, and severe obstructive sleep apnea (OSA) was referred after a recent diagnosis of myotonic dystrophy type 1 (DM1) for EDS. He presented with foot pain, balance issues, and falls. A subdural hemorrhage from a fall prompted thorough evaluation including electromyography. This showed length-dependent polyneuropathy type pattern with features of subacute and chronic denervation change and myotonic discharges in right vastus medialis and bilateral tibialis anterior and gastrocnemius muscles. Myotonic Syndrome Advanced Evaluation revealed with a repeat expansion mutation in DMPK gene (85 and 13 CTG repeats). He was previously diagnosed severe OSA with an AHI of 64 and titrated onto bilevel. He recalled no improvement in symptoms with bilevel. He noted sleeping 10-12 hours per night and feeling rested. However, he takes multiple times per day for hours at a time. When actively working on tasks he feels alert and focused. Epworth sleepiness scale (ESS) was 12. Polysomnogram on bilevel followed by MSLT demonstrated control of OSA and mean sleep onset latency of 8 minutes and 5 sleep onset REM periods. With relatively little impairment and a desire for intermittent improved wakefulness, he was started on modafinil 200mg daily as needed. He reported a robust response to modafinil without the need for additional naps or cardiac complications thus far. Repeat ESS only improved to 10. Conclusion This case highlights the need for a precision medicine approach as subpopulations exist even within the specific diagnosis excessive daytime sleepiness in myotonic dystrophy. People with DM1 have been similarly reported with little improvement in ESS but dramatic subjective improvement in symptoms with modafinil. A Cochrane Review and a European Medicines Agency recommendations on modafinil are not supportive of its use in DM1 despite a subpopulation with a clear response. Interestingly, clinical measures do not seem to predict response to modafinil, suggesting unmeasured and, potentially, varied pathologies of excessive daytime sleepiness in DM1. Support (if any)