Patient 1 was a 52-year-old woman with aSAH. Until day 3, she had 13 SDs (2 spreading depressions and 11 isoelectric SDs) with a PTDDD of 487.9 minutes that occurred on day 3. On the same day, a computed tomography (CT) scan showed multiple infarcts in the territories of the right middle cerebral artery (MCA) and both posterior cerebral arteries. On the following day, a control scan revealed increasing lesions, 10mm midline shift, and beginning brain herniation. From the beginning, she required intravenous noradrenaline at a rate of 0.08 µg/kg/min to maintain adequate cerebral perfusion pressure (CPP) under sedation with propofol. Stress cardiomyopathy was ruled out using echocardiography, electrocardiography, and cardiac biomarkers. However, noradrenaline had to be further increased to 0.26 µg/kg/min on day 4 when she developed Staphylococcus aureus–caused pneumonia and midazolam was added to the sedative regimen to control progressive increase in ICP. Thiopental was added for the same reason 12 hours before she died on day 6. Thiopental resulted in cerebral isoelectricity, and intravenous noradrenaline had to be increased to a rate of 0.43 µg/kg/min. Eventually, a DNR-CC order was activated after family discussion and the patient was terminally extubated. Withdrawal of the life-sustaining treatment resulted in complete circulatory arrest after 17 minutes. Figure A shows the time course of the systemic arterial pressure including the circulatory arrest and subsequent terminal SD that started at electrode 4 and then spread to the other electrodes. For comparison, Figure C displays a typical terminal SD of a rodent brain after injection of air into the heart via the femoral vein (experimental setup in Fig D); circulatory arrest is followed by nonspreading depression and then terminal SD. The Supplementary Table provides the statistical data of 5 thiopental-anesthetized rats with previously healthy brains in which death resulted from sudden circulatory arrest by air injection into the femoral vein.
Patient 3, a 78-year-old woman, showed large bifrontal ICH in addition to aSAH. She had 12 SDs on days 2 and 3, and 1 on day 10. One SD was a spreading convulsion. The others were classified as spreading depressions. The PTDDD was 144.1 minutes and occurred on day 2. Her past medical history was significant for liver cirrhosis of unknown etiology. During her clinical course, she developed a hepatorenal syndrome with progressive failure of liver, kidneys, lungs, and circulation. A family discussion was held and a DNR-CC order was activated followed by terminal extubation on day 11. As shown in Figure A, the ECoG showed a deviation from the 2 previous cases because the terminal SD started in electrode 3 at 7 minutes before the circulatory arrest. In this moment, spontaneous brain activity was still present. Accordingly, the terminal SD induced spreading depression at electrode 3. From electrode 3, the SD spread to the other electrodes. Finally, nonspreading depression rendered the remaining spontaneous brain activity isoelectric while the terminal SD was still propagating. Presumably, the last SD originated from the rim of the previous ICH. The circulatory arrest then converted this SD into a terminal one.