By Alexander E. Merkler, MD
Assistant Professor of Neurology and Neuroscience, Weill Cornell Medical College, and Assistant Attending Neurologist, NewYork-Presbyterian Hospital
Dr. Merkler reports no financial relationships relevant to this field of study.
Traumatic microbleeds are common in patients with any severity of traumatic brain injury and may be a useful biomarker to predict clinical outcomes.
Griffin AD, Turtzo LC, Parikh GY, et al. Traumatic microbleeds suggest vascular injury and predict disability in traumatic brain injury. Brain 2019;142:3550-3564.
Traumatic brain injury (TBI) is common. Each year, there are approximately 2.5 million emergency department visits for TBI in the United States alone.1 Although many patients with TBI recover, more than 3 million Americans live with disability due to TBI.2 Given the heterogeneity of severity, etiology, and type of TBI, it often is difficult to predict who will develop disability, especially among patients with mild TBI in whom initial clinical examination and computed tomography (CT) scans may be normal. Therefore, discovering novel biomarkers that may aid in the diagnosis and prognosis of TBI is essential and may lead to targeted therapies to improve outcomes.
In this prospective, observational study, Griffin et al evaluated the prevalence and significance of traumatic microbleeds on brain magnetic resonance imaging (MRI) among patients with TBI. Specifically, the authors sought to 1) evaluate the frequency of traumatic microbleeds among patients with TBI; 2) evaluate whether traumatic microbleeds were associated with disability after TBI; and 3) elucidate the underlying pathology of traumatic microbleeds. The study included all patients with TBI who received a head CT; they were enrolled within 48 hours of injury and received research MRI. The Glasgow Outcome Scale-Extended was used to evaluate disability (defined as a score of ≤ 6) at a 30- or 90-day follow-up visit. Binary logistic regression was used to evaluate the association between the presence of traumatic microbleeds and disability after adjustment for trauma severity, Glasgow Coma Scale (GCS) score, time to MRI, and presence of injury on CT.
A total of 439 patients were included in the study: 365 (83%) had mild TBI, 55 (13%) had moderate TBI, and 19 (4%) had severe TBI. Traumatic microbleeds were defined as small foci of hypointensity seen on the initial T2*-weighted MRI. Two types of microbleeds — punctate and linear — were found. Microbleeds were found in 27% of patients with mild TBI, 47% of patients with moderate TBI, and 58% of patients with severe TBI. Not surprisingly, injury severity, GCS at time of arrival, and evidence of injury on the initial CT all were significantly associated with the presence of traumatic microbleeds. Among the 250 (55%) patients who had a 30- or 90-day follow-up visit, the presence of traumatic microbleeds was associated with disability at the time of follow-up (odds ratio, 2.5).
To better understand the underlying etiology of traumatic microbleeds, the investigators performed an autopsy with postmortem brain imaging on a single patient with severe TBI who had evidence of traumatic microbleeds on MRI. Interestingly, when the investigators evaluated the tissue histopathology that correlated to the area of traumatic microbleed on MRI, there was no evidence of axonal injury. Instead, the investigators found evidence suggesting that traumatic microbleeds may represent vascular injury. The microbleed seen on brain MRI may merely represent a small fraction of the tissue-level vascular injury that is too microscopic to visualize on present-day brain imaging.
COMMENTARY
The authors of this prospective, observational study demonstrated that traumatic microbleeds are common in TBIs of all severity. In addition, the authors suggested that traumatic microbleeds may be a useful biomarker to predict clinical outcomes, although these results are limited by selection bias and likely by residual confounding. Further studies will be necessary to evaluate the significance of traumatic microbleeds and whether their presence may explain why patients with TBI who have grossly normal clinical exams and head CT scans go on to have significant neuropsychological disability.
Finally, the investigators reported intriguing findings that challenge the currently accepted belief that traumatic microbleeds represent diffuse axonal injury. Instead, the investigators purported that traumatic microbleeds could represent vascular injury. If replicated, further study of vascular injury, and conceivably therapeutics, to promote vascular recovery could be implemented in patients with TBI.
REFERENCES
- Taylor CA, Bell JM, Breidling MJ, Xu L. Traumatic brain injury-related emergency department visits, hospitalizations, and deaths - United States, 2007 and 2013. MMWR Surveill Summ 2017;66:1-16.
- Zaloshnja E, Miller T, Langloi JA, Selassie AW. Prevalence of long-term disability from traumatic brain injury in the civilian population of the United States, 2005. J Head Trauma Rehabil 2008;23:394-400.
