- 1. The blood–brain barrier (BBB) protects the brain from circulating xenobiotic agents. The pathophysiology, time span, spatial pattern, and pathophysiological consequences of BBB disruptions are not known. 2. Here, we report the quantification of BBB disruption by measuring enhancement levels in computerized tomography brain images. 3. Pathological diffuse enhancement associated with elevated albumin levels in the cerebrospinal fluid (CSF) was observed in the cerebral cortex of 28 out of 43 patients, but not in controls. Four patients displayed weeks-long focal BBB impairment. In 19 other patients, BBB disruption was significantly associated with elevated blood pressure, body temperature, serum cortisol, and stress-associated CSF “readthrough” acetylcholinesterase. Multielectrode electroencephalography revealed enhanced slow-wave activities in areas of focal BBB disruption. Thus, quantification of BBB disruption using minimally invasive procedures, demonstrated correlations with molecular, clinical, and physiological stress-associated indices. 4. These sequelae accompany a wide range of neurological disorders, suggesting that persistent, detrimental BBB disruption is considerably more frequent than previously assumed.