It started as a medical mystery and became a cautionary tale. Fatal hemorrhages occurred in the brains of two patients several days after successful cerebral aneurysm treatment with the Pipeline™ Embolization Device (PED). These hemorrhages were located in the same vascular territory as the treated aneurysms but were not close enough to the lesions to be directly linked to the aneurysms or their treatment. Over time, physicians began to suspect that these were not isolated hemorrhages, but in fact, were occurring in approximately 4% of patients treated in this manner. In the second patient (Case 1 in this paper), embolic non-biological material had been found close to the site of hemorrhage, but the nature of the material and its relationship to the hemorrhage was unclear. When a third patient at a distant institution (Case 2) developed a similar delayed hemorrhage, the treating physicians were advised to check carefully for the presence of embolic foreign material. When the material was confirmed to be present in the third patient (Case 2), preserved tissue from the first patient (Case 3) was re-examined and the embolic material, albeit in lesser amounts, was identified adjacent to the hemorrhagic area. The source of this material became the next question to answer.
Autopsy specimens in all three patients contained collections of non-biological material at the site of brain hemorrhage. Tests showed this material to be polyvinylpyrrolidone (PVP), a water-soluble polymer with various applications such as an adhesive in glue sticks, a binder in pharmaceutical tablets, and a lubricant coating in catheters. Deposits of PVP were found in the hemorrhagic areas, clogging blood vessels and extending into surrounding brain tissue. The only other place in the brain that PVP was found was on the surface of the PED in two of the patients. Since the PED does not contain PVP, the researchers focused on other materials used in the endovascular procedure. They suspect that the PVP sloughed off the Cook Shuttle Guiding Sheath that was used to deliver the PED, and they provide videos showing how this may have occurred. The PVP may then have traveled through the vasculature from the site of aneurysm treatment to the location where hemorrhage later occurred.
The researchers discuss the role PVP could have played in the fatal hemorrhages. However, they note that there is no clear-cut evidence that the presence of PVP was the direct or sole cause of fatal brain hemorrhage in these patients. PVP is a component in numerous supplies used in endovascular procedures, and its presence has not been directly linked with catastrophic events. In addition, there are other factors that could cause brain hemorrhage in patients undergoing aneurysm treatment.
The researchers describe and discuss additional potential causes of hemorrhage as well as the possibility that a combination of two or more factors, including PVP, could lead to this serious event. All are detailed in their paper, "Histopathological assessment of fatal ipsilateral intraparenchymal hemorrhages after the treatment of supraclinoid aneurysms with the Pipeline Embolization Device. Report of 3 cases" by Yin C. Hu, M.D., Vivek R. Deshmukh, M.D., Felipe C. Albuquerque, M.D., David Fiorella, M.D., Ph.D., Randal R. Nixon, M.D., Ph.D., Donald V. Heck, M.D., Stanley L. Barnwell, M.D., Ph.D., and Cameron G. McDougall, M.D., F.R.C.S.C., published today online, ahead of print, in the Journal of Neurosurgery.
Despite no indisputable "smoking gun" in these cases, the researchers emphasize that the finding of PVP in cerebral arteries is "a cause of serious concern." They point out that it is possible that some ischemic complications that occasionally occur after endovascular procedures may be due to PVP-clogged arteries that didn't rupture. The researchers urge that more research should be conducted on the relationship between PED procedures and the presence of embolic foreign bodies in the vasculature. The researchers also caution that "a better understanding of the risks associated with particular endovascular devices and combinations of devices is required so that appropriate solutions may be engineered to minimize the risk" to patients.
When asked about the take-home message of this study, Dr. Cameron McDougall of Barrow Neurological Institute said that the discovery of PVP and the possible association between its presence and delayed hemorrhage following PED treatment "only came to light because a group of committed individuals cared deeply about this, communicated their concerns, and worked together to try to understand a problem that none could answer on their own. I think [the study] highlights the importance of vigilance and collaborating, especially around events which are infrequent."