Believed to be due to unbalance between cerebrospinal fluid (CSF) production rate and its loss through the spinal dural puncture hole, post-dural puncture headache (PDPH) is often considered as a physiological syndrome, usually reversible without pathological sequelae after dural hole's closure. The clinical case here presented (incapacitating headache associated with diagnostic dural puncture in a leukaemic young female patient who underwent bone marrow transplantation) shows potentially fatal pathological sequelae following prolonged headache (untreated, due to the severe postransplant immunodeficiency and coagulopathy). The observed RMI lesions suggest interesting conclusions about the clinical indications and correct timing of autologous epidural blood patch (EBP). We also suggest the ways to preventing rebound intracranial hypertension following autologous epidural blood patch in patients suffering from incapacitating and prolonged headache.