Introduction: Natalizumab break exposes multiple sclerosis (MS) patients to a high risk of disease reactivation or rebound, whose prevention and treatment constitute a clinical challenge. Case presentation: We describe a dramatic case of MS rebound, characterized by the development of severe neurological and psychiatric symptoms, following natalizumab break. Alemtuzumab rapidly and completely suppressed brain inflammation as demonstrated by clinical and radiological findings. Conclusions: Our case further adds to the available literature evidence on Alemtuzumab as first-choice rescue therapy following Natalizumab discontinuation
