Blood biomarkers have limitations, however. Although they are highly expressed in CNS, they are detected in low concentrations in serum. In addition, blood biomarkers such as S100 beta have sources outside the brain, thus they are not specific to concussion. Finally, the precision of current immunoassays for these biomarkers needs improvement, said Dr. Dodick.
Imaging Biomarkers
Imaging biomarkers also could support a diagnosis of concussion. In one study, 142 patients with concussion underwent gadolinium-enhanced MRI scans within 48 hours of injury. Meningeal hemorrhage was seen on CT in about 13% of participants, but almost half had focal gadolinium enhancement on MRI. The results indicate a possible breakdown of the blood–brain barrier, said Dr. Dodick.
An investigation published in Annals of Neurology examined 135 patients with concussion and a normal CT of the head. Approximately 30% of participants had abnormal brain MRI scans. Findings included sulcal subarachnoid hemorrhage, hemosiderin deposition, and focal contusions.
In a study published in 2015 in Neurology, researchers found 60 microbleeds in 26 patients with concussion, compared with 15 microbleeds in 12 control subjects. Approximately 90% of the microbleeds in participants with concussion were cortical or subcortical, compared with 20% in controls. Patients with concussion and microbleeds have poor short-term memory and other neuropsychologic deficits on examination. Microbleeds resulting from concussion usually occur at the juncture of gray matter and white matter, said Dr. Dodick.
Lobar cerebral microbleeds appear to be a biomarker of severity and to indicate risk of adverse long-term outcomes. This biomarker can inform decision-making and is ready to be integrated into clinical practice, said Dr. Dodick.
In another study, 45 male and female university-level ice hockey players underwent susceptibility-weighted imaging before and after the playing season, as well as 72 hours, two weeks, and two months after a concussion. The investigators saw a significant increase in cerebral microbleeds in male athletes at two weeks after concussion, and a significant increase in microbleeds in males without concussion, compared with females, at the beginning and end of the season.
—Erik Greb