Regional changes in cerebral blood flow may guide concussion management.
In my column in January, I discussed results of a study on blood biomarkers for concussion -- a study which many suggested painted a poor picture for the scientific likelihood of clinically useful blood biomarkers. At the time, I argued that there was good reason to still hope that blood biomarkers could have clinical relevance if researchers elucidated a tricky concept called "glymphatic clearance." However, a new study this week makes me wonder whether tricks will actually be necessary.
Many studies have shown reduced cerebral blood flow (CBF) in moderate to severe traumatic brain injury (TBI) and in animal models of concussion, but none have ever prospectively demonstrated decreased regional CBF in concussed humans. Theories of concussion pathophysiology converge on the concept of reduced blood flow connected to altered brain metabolism. Therapies which may help improve concussion symptoms, such as exercise, seem to work by restoring CBF by impact on cerebral autoregulation.
Finally, JAMA Neurology published a study this week (summarized earlier this week on MedPage Today) that supports these theoretical principles and suggests a potential role for changes in regional CBF as a marker for concussion. Using specialized voxelwise analysis to determine the precise location of blood flow changes as opposed to looking at global cerebral perfusion, the researchers demonstrate recovery of CBF in the right insular and superior temporal cortex commensurate with symptom recovery. More significantly, they found that CBF in one specific region, the dorsal midinsular cortex (DMC), was decreased at one month in athletes that were slower to recover from symptoms and the decrease was inversely related to the magnitude of initial psychiatric symptoms of depression and anxiety.
The study has numerous and important ramifications. As differences in regional CBF were demonstrable cross-sectionally as compared with controls, measurement of regional CBF could provide objective data for the diagnosis of concussion. As improvement in regional CBF correlated with symptomatic improvement, it could also be used to track concussion recovery. This could guide decisions of return-to-learn and return-to-play, decisions currently relying solely on symptom expression.
To me, the most profound implication of this study is the findings in the DMC. Increased psychiatric symptoms at presentation suggest greater decrease in DMC CBF, providing prognostic potential early after injury. Additionally, a variety of concussion symptoms like dizziness and imbalance can be localized to this area, creating opportunity for future studies to examine this area more closely for pathophysiologic understanding. This may even offer therapeutic opportunities in determining ways to restore CBF to the DMC early on to reduce symptom duration.
However, I have to add a bit of caution to my enthusiasm over the study results. As the authors note, the study is small, with only 17 cases and 27 controls, and the patient population is very homogeneous (all collegiate football athletes), raising concerns about sampling bias and generalizability. Larger studies examining a more diverse population, especially a range of patient ages, will help better understand the diagnostic, prognostic, and therapeutic potentials of these findings. They may also help determine whether the effect is directly measurable; in other words, could regional CBF be calculated at time of presentation, would the amount give sensitive and specific prognostic information, and could it be tracked over time to confirm recovery and identify those at risk for persistent symptoms.
Despite its limitations, this study offers great opportunity for future science and management in concussion. It brings us one step closer to unraveling the mystery of concussion pathophysiology and provides hope for the millions of people who suffer from concussion each year.