A fourth line of indirect evidence is that when EPI-743 is effective in treating mitochrondrial disease, brain regions with very low HMPAO uptake show a marked increase in uptake. In the case of TS (50 cases and 20 controls) HMPAO uptake was found to be reduced in the left caudate, anterior cingulate cortex and the left dorsolateral prefrontal cortex. Severity of tics was related to hypoperfusion of the left caudate and cingulate and a left medial temporal region.