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Background: The present study evaluates the types and dynamics of intracranial pathological changes in patients with severe traumatic brain injury (sTBI) who participated in a prospective, randomized, double-blinded study of add-on treatment with prostacyclin. Further, the changes of brain CT scan and their correlation to Glasgow Coma Scale score (GCS), maximal intracranial pressure (ICP(max)), minimal cerebral perfusion pressure (CPP(min)), and Glasgow Outcome Score (GOS) at 3, 6, and 12 months were studied., Methods: Forty-eight subjects with severe traumatic brain injury were treated according to an ICP-targeted therapy protocol based on the Lund concept with the addition of prostacyclin or placebo. The first available CT scans (CT(i)) and follow-up scans nearest to 24 h (CT(24)) were evaluated using the Marshall, Rotterdam, and Morris-Marshall classifications., Results: There was a significant correlation of the initial Marshall, Rotterdam, Morris-Marshall classifications and GOS at 3 and 12 months. The CT(24) Marshall classification did not significantly correlate to GOS while the Rotterdam and the Morris-Marshall classification did. The CT(i) Rotterdam classification predicted outcome evaluated as GOS at 3 and 12 months. Prostacyclin treatment did not influence the dynamic of tissue changes., Conclusions: The Rotterdam classification seems to be appropriate for describing the evolution of the injuries on the CT scans and contributes in predicting of outcome in patients treated with an ICP-targeted therapy. The Morris-Marshall classification can also be used for prognostication of outcome but it describes only the impact of traumatic subarachnoid hemorrhage (tSAH).