The aim of this study is to identify the pathophysiology of migraine attack with prolonged aura (between 1 h and 7 days) not clearly understood. We studied cortical cerebral microcirculation by an innovative near infrared spectroscopy system (NIRS) and cerebral macrocirculation by transcranial Doppler (TCD) in eight subjects (3 M and 5 F, age range 21-41 years) during spontaneous prolonged migraine aura and after 1, 2, 4, 6, 12 and 24 h since the end of aura and compared the results with the headache-free periods. During aura NIRS showed a significant decrease of the arterial pulse wave of cerebral microcirculation (APWCM) amplitude (-35%), p < 0.002, and an increase of cerebral tissue oxygen saturation (SctO(2)) (+15%), p < 0.008 ipsilateral to the headache pain and contralateral to the symptoms of aura compared with the headache-free periods; TCD showed a significant increase of pulsatility index (+38%), p < 0.001 and a significant decrease of the diastolic velocity in the posterior and middle cerebral artery ipsilateral to the headache pain and contralateral to the symptoms of aura compared with the headache-free periods. During prolonged migraine aura we found areas of cortical hypoperfusion corresponding to the topography of aura symptoms that were the result of a decreased metabolic demand rather than ischemic mechanism.