Matthew Edwardson, MD

Mazya MV, Ahmed N, Ford GA, Hobohm C, Mikulik R, Nunes AP, and Wahlgren N. Remote or Extraischemic Intracerebral Hemorrhage—An Uncommon Complication of Stroke Thrombolysis: Results From the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register. Stroke. 2014

Intraparenchymal hemorrhage remote (PHr) from the area of focal ischemia is an uncommon complication of IV-TPA treatment. Rates of PHr were difficult to extract in prior stroke trials because they were often grouped together with rates of intraparenchymal hematoma (PH) – hemorrhage within the existing ischemic stroke bed. Herein Mazya and colleagues describe the first comprehensive study of PHr using data from a huge stroke registry. They show previously unknown risk factors for PHr and an intermediate prognosis for recovery.

The authors performed a retrospective analysis of prospectively collected data from the SITS-International Stroke Thrombolysis Register (SITS-ISTR), which contains demographic and neuroimaging data from 43,494 patients treated with IV-TPA. They found rates of PHr, PH, and PHr + PH of 2.2%, 5.5%, and 1% respectively. A comparison of risk factors for PHr vs. PH showed that PHr patients were more likely to have remote prior infarct (OR 1.3), female gender (OR 1.23), and older age (OR 1.09). Mortality rates at 3 mo. were lower for those with PHr (33.9%) than for those with PH (39.2%) and PHr + PH (62.1%), but higher than for those with no intracranial bleeding (12.1%).

This is by far the most comprehensive study of PHr to date. Although PHr is relatively uncommon (3.2% if one includes both PHr and PH + PHr), this underappreciated complication of IV-TPA increases morbidity and mortality and therefore warrants further study. The authors made huge strides in this regard, uncovering risk factors specific to PHr including remote prior infarct and female gender. Despite these associations, the authors note relatively low odds ratios for each risk factor and suggest that another variable not collected in SITS-ISTR may be more important in predisposing patients to PHr. They suggest cerebral amyloid angiopathy (CAA) as a possibility given the association between CAA and female gender. I would offer another – prior head trauma. Even patients with mild concussion often show evidence of blood-brain-barrier disruption on acute MRI. Such disruption could make patients more susceptible to hemorrhagic conversion in the setting of future IV-TPA administration. Whatever the cause, this study definitely raises awareness of the importance of PHr and will prompt future investigations.