Diagnostic and therapeutic challenges in narcolepsy: From childhood to complex comorbidity through 3 clinical cases

Introduction: Narcolepsy is a chronic neurological disorder characterized by excessive daytime sleepiness and abnormal rapid eye movement manifestations, such as cataplexy, sleep paralysis, and hypnagogic hallucinations. Symptoms usually begin in childhood or adolescence, and diagnosis is often delayed. Treatment typically involves wake-promoting agents, antidepressants, and more recently, histamine H3 receptor antagonists like pitolisant. Given its complexity, real-world evidence on treatment strategies is needed. Objectives and Patients: This study describes three clinical cases of narcolepsy treated with pitolisant and followed longitudinally, focusing on clinical response, dose adjustments and functional outcomes. Case one involves an eight-year-old girl with excessive daytime sleepiness, later developing cataplexy. Pitolisant was titrated to 18 mg/day. In case two, a six-year-old boy presented with severe hypersomnia, cataplexy, hallucinations, and Tanner stage II pubertal development. Pitolisant started at 4.5 mg/day, increased to 9 and then 13.5 mg/day. Case three concerns a 49-year-old man whose childhood-onset symptoms evolved into hypersomnolence, snoring, and non-restorative sleep. Pitolisant was started at 9 mg/day, increased to 36 mg/day, then reduced to 18 mg/day. Results: At five months, case one reported near-normal functioning. In case two, daytime sleepiness resolved, school attendance resumed, weight stabilized, and pubertal progression halted. In case three, Epworth Sleepiness Scale scores dropped, and the patient remained stable. Conclusions: These cases illustrate diagnostic complexity and the need for personalized treatment. Pitolisant proved effective in improving excessive sleepiness, cataplexy, and functioning. The findings underscore the importance of early diagnosis, tailored pharmacotherapy, and real-world clinical data to refine management, especially in complex cases. Introducción: La narcolepsia es un trastorno neurológico crónico caracterizado por somnolencia diurna excesiva y alteraciones del sueño REM, como cataplejía, parálisis del sueño y alucinaciones hipnagógicas. Los síntomas suelen comenzar en la infancia o adolescencia, con frecuente retraso diagnóstico. El abordaje terapéutico incluye agentes promotores de la vigilia y antidepresivos, y recientemente se ha incorporado el antagonista H3 de histamina pitolisant. Dada la complejidad fisiopatológica del trastorno, resulta imperativa la generación de evidencia práctica sobre estrategias de manejo terapéutico. Objetivos y Pacientes: Este estudio describe tres casos clínicos de narcolepsia tratados con pitolisant y seguidos longitudinalmente, enfocándose en la respuesta clínica, ajustes de dosis y resultados funcionales. El caso uno corresponde a una niña de ocho años con somnolencia diurna y cataplejía, tratada con pitolisant hasta 18 mg/día. El caso dos refiere a un niño de seis años con hipersomnia severa, cataplejía, alucinaciones hipnagógicas y desarrollo puberal estadio II de Tanner, con incremento de dosis hasta 13,5 mg/día. El caso tres describe a un hombre de 49 años con síntomas desde la infancia, evolucionando a hipersomnia, ronquidos y sueño no reparador. Se tituló pitolisant hasta 36 mg/día, luego reducido a 18 mg/día. Resultados: A los cinco meses, la primera paciente recuperó funcionalidad casi normal. En el segundo, se resolvió la somnolencia y se reanudó la asistencia escolar. El tercero mostró descenso en la Escala de Somnolencia de Epworth y estabilidad clínica. Conclusiones: Los casos destacan la complejidad diagnóstica y la necesidad de tratamiento individualizado. Pitolisant demostró eficacia clínica y funcional.