Traumatic microbleeds (TMBs) may indicate vascular injury and predict worse outcomes after even minor brain injury, according to a study at the National Institute of Neurological Disorders and Stroke.
The study involved 439 adults with head injuries treated in the emergency department. The participants had magnetic resonance imaging (MRI) scans within 48 hours of the injury and again during 4 subsequent visits. They also completed behavioral and outcome questionnaires.
Microbleeds appear as small dark lesions on MRI scans but are usually too small to be seen on computer tomography (CT) scans. Sometimes they appear as dots (punctate), sometimes they are linear. In previous studies, researchers examined TMBs in the acute phase of traumatic brain injury (TBI) and stroke and found linear-appearing TMBs only in patients with TBI, suggesting that at least linear TMBs are consistent with trauma and might be the result of injured vessels. They conjectured that TMBs seen on MRI might be a form of traumatic vascular injury distinct from primary injury to the axons.
In this study, one-third of the patients had TMBs. More than half (58%) of the participants with severe head injury showed microbleeds, as did 27% of patients with mild injuries. In most patients with microbleeds, they appeared as linear streaks or dotted lesions. The study also revealed that the frontal lobes were the region most likely to show microbleeds.
The researchers controlled for variables known to predict poor outcome, such as trauma level and trauma-related injury on CT. Even so, microbleeds significantly predicted worse outcome. Patients with both punctate and linear TMBs were twice as likely to have disability (Glasgow Outcome Scale-Extended ≤6) on follow-up.
One participant’s family donated his brain for further analysis after he died. Imaging with a more powerful MRI scanner and a detailed histologic analysis allowed the researchers to better understand the pathology.
The researchers found that what appeared as a punctate TMB on MRI corresponded to iron-laden macrophages in the perivascular space surrounding a vascular tree that extended over centimeters. That was surprising, the researchers say. They expected to see iron within the parenchyma, but they also found iron inside macrophages outside of the parenchyma between the vessel and neuropil, tracking alongside vessels.
The researchers say that finding signified that the extent of injury was more extensive than indicated on MRI and had consequences to cellular function over a larger area of brain. In fact, they suggest, punctate and linear TMBs may not be distinct entities: The difference in shape may be “an issue of resolution.”
The researchers conclude that TMBs could be biomarkers for vascular injury. They also note that the leakage of blood from damaged blood vessels can trigger an inflammatory response. The damage to vessels, the disruption of normal pathways of blood flow, and the influx of inflammatory cells could result in secondary injury to the brain tissue due to ischemia.
Thus, TMBs may also be useful biomarkers for identifying which patients are candidates for treatments that reduce ischemic damage or improve microvascular cerebral blood flow.