Microbleeds After Head Trauma Lead to Worse Neurological Outcomes
By Kurt Samson
November 21, 2019
Article In Brief
Investigators reported that traumatic microbleeds were prevalent in mild and more severe head injury cases. They suggest that recognizing these microbleeds as a form of traumatic vascular injury may help identify patients who could benefit from therapies targeting the injured vasculature and secondary injury to parenchyma.
Head trauma can cause microbleeds in brain tissue, contributing to worse neurological and functional outcomes, according to a new report by researchers at the National Institute for Neurological Disorders and Stroke (NINDS).
Until now, most brain injury experts have believed that axonal damage was responsible, said Lawrence Latour, PhD, the senior author of the study.
“These findings, if confirmed, may represent that injury to blood vessels can occur, even after minor head injury,” he told Neurology Today.
Dr. Latour said that while damage to brain cells can be devastating, the exact nature and impact of vascular injury from head trauma is uncertain and requires further study.
The findings, published in the November 1 issue of Brain, were based on an analysis of data from several types of advanced MRI performed on 439 head injury patients, all adults, who underwent scans within 48 hours of injury, and again during four subsequent visits. The researchers then examined scans from advanced diffusion tensor imaging to estimate the location, orientation, and crystal-like properties of aberrant properties. They then compared the imaging data with information collected from behavioral and outcome questionnaires.
The researchers found that 31 percent of milder head injury cases had evidence of microbleeds, as did 58 percent of patients with more severe trauma to the head.
Microbleeds appeared as either linear streaks or “dotted” injury—or punctate lesions—but a majority of those with microbleeds had both types. The findings also showed microbleeds were most often located in the frontal lobes.
The researchers also reported that patients with microbleeds were more likely to develop a greater level of disability compared with the others.
One participant died following completion of the study, and the family donated the brain for further analysis. Dr. Latour's team imaged the brain with a more powerful MRI scanner and conducted detailed histological analysis, allowing the pathology underlying the traumatic microbleeds to be better described. The results showed iron, indicating blood, in macrophages tracking along the vessels seen on the initial MRI as well as in extended areas beyond those seen on MRI.
“Combining these technologies and methods allowed us to get a much more detailed look at microbleed structure and get a better sense of just how extensive they are,” said Allison Griffin, a graduate student and first author of the paper.
The investigators also noted that microbleeds after brain injury might serve as a possible biomarker for patients who may be candidates for therapies that specifically target vascular injuries.
They added that additional study will be necessary in order to evaluate any additional effects of microbleeds and to find the best way to manage them in order to reduce disability and find other ways to treat them. Future studies will also help clinicians decide which patients should undergo specific imaging following head injury. At present there is no evidence that MRI scans should be used in place of CT scans for patients suspected to have experienced head injury, they said.
For the study, patients with acute head trauma at one emergency department who received a head CT were enrolled within 48 hours after injury and were given a research MRI. The Glasgow Outcome Scale-Extended was greater than 6 at follow-up.
All MRIs were interpreted prospectively and were used for subsequent analysis of traumatic microbleeds and stratified based on linear streak-like or punctate petechial-appearing traumatic microbleeds.
The brain of one subject was procured following death for evaluation of traumatic microbleeds using MRI targeted pathology methods. Of the 439 patients enrolled over 78 months, 31 percent had evidence of punctate and/or linear traumatic microbleeds on MRI. Severity of injury, mechanism of injury, and CT findings were associated with traumatic microbleeds on MRI.
The presence of traumatic microbleeds was an independent predictor of disability (p<0.05; odds ratio=2.5), but no differences were found between patients with punctate versus linear-appearing microbleeds. Post-mortem imaging and histology revealed traumatic microbleed co-localization with iron-laden macrophages, predominately in the perivascular space.
Notably, no evidence of axonal injury was seen in co-localized histopathological sections. While axonal injury in association with traumatic microbleeds cannot be excluded, the researchers said, recognizing traumatic microbleeds as a form of traumatic vascular injury may aid in identifying patients who could benefit from new therapies targeting the injured vasculature and secondary injury to parenchyma.
Commenting on the study, Max Wintermark, MD, professor of radiology and chief of neuroradiology at Stanford University Medical Center, said: “We use susceptibility weighted MR imaging, the technique described in the article, routinely to evaluate our patients suspected of traumatic brain injury. Therefore, this article was very relevant to our clinical practice.”
“The most surprising result to me was that the authors were not able to find signs of diffuse axonal injury on pathology in the areas with microbleeds on imaging,” Dr. Wintermark said. “In the clinical setting, we typically interpret the presence of microbleeds on imaging as a hallmark of diffusion injury, however, this article challenges this interpretation.”
He added that more research is needed to validate the research, as well as to determine whether microbleeds remain an indicator of diffuse axonal injury, even if this injury may not be confined to the local area around the microbleed.
Alan I. Faden, MD, FAAN, the David S. Brown Professor in Trauma and director of the Center for Shock, Trauma & Anesthesiology Research at the University of Maryland School of Medicine, noted that detection of traumatic microbleeds on MRI was found in 31 percent of TBIs where CT scans were performed.
Dr. Faden said that it is significant that most of these patients had mild TBI, and the evidence that microbleeds were an independent predictor of subsequent disability could be quite significant.
“Comparing post-mortem ex vivo imaging and histology demonstrated that microbleeds were co-localized with iron-laden macrophages, but not with axonal injury,” he continued. “This study shows that microbleeds are common in mild TBI and predict worse outcome, and as TBI is perhaps the most heterogeneous of neurological disorders, the presence or absence of microbleeds by MRI scan may prove helpful for classifying the pathobiological patterns of injury, for evaluating effectiveness of potential new treatments in patient sub-populations, and for predicting longer-term disability.”
Drs. Latour, Wintermark, and Faden had no competing interests.