The difficult path to diagnosis

This exercise is a part of Educator Guide: Concussion Leaves Clues in the Blood / View Guide

Directions for teachers:
After students have read “Concussion leaves clues in the blood,” lead a class discussion based on the first set of questions below. The prompts encourage students to use their own experience as a starting point to think about the various signs and symptoms of injury or disease.

After the class discussion, ask students to break out into partners or small groups to explore biomarkers in particular. Once students have covered the last question, bring the class together to share any final thoughts.

Class discussion questions

1. Think about the last time you or someone you know was injured. What did people (parents, athletic trainers, nurses, doctors, for example) do to try to diagnose the problem or its extent? What questions did they ask? What types of tests and procedures, if any, were run and what kind of information did those tests provide?

2. Now broaden your thinking. What techniques or tools do doctors or other medical professionals have available to identify injuries more generally? What about diseases and other health problems? Be sure to consider low-tech approaches and more high-tech tools.

3. Why are some health problems harder to diagnose than others? What characteristics of the injury or disease might influence the ease of identifying the problem? How might differences among individuals affect the ability to make a diagnosis? Why do you think doctors often rely on multiple lines of evidence for a diagnosis?

Partner discussion questions

4. What are biomarkers? How might biomarkers be useful in diagnosing concussions? Can you think of other diseases or injuries where biomarkers might be useful? Do a quick search at to find examples of potential biomarkers that researchers are currently exploring.

Biomarkers are chemical signals that may indicate a medical state, such as a concussion. Scientists hope to find biomarkers that can be paired with other signs and symptoms, such as physical assessments and memory tests, to help diagnose concussions. Researchers are currently exploring biomarkers that might someday help diagnose autism, pancreatic cancer and Alzheimer’s disease, as just a few examples.

5. How do biomarkers compare with other types of tests? What are the benefits and limitations of biomarkers? For the concussion study described in the article, did the researchers show that a knock to the head caused an increase in the biomarkers? Did the increase in the biomarkers cause the loss of normal brain function? Explain. Are there other cases when biomarkers can play a causative role?

Biomarkers offer a window into what is happening within the body. They may be less subjective than tests that rely on recall or reported symptoms and less invasive than tests that need to study tissue directly. Still, biomarkers are just one source of evidence and often can’t be used to make a diagnosis on their own. They require preexisting knowledge of baseline levels and in some cases may be misinterpreted. 

In the case of the concussion research described in the article, the researchers did not prove that a knock to the head caused the biomarker levels to increase. The researchers instead reported an association between a concussed state and biomarker levels. Factors other than the knock on the head could have affected the protein levels, which might make them a red herring for researchers. Likewise, it’s unclear whether the presence of the biomarkers contributes to the loss of normal brain function; it’s likely that they are an indirect sign that the damage has happened. In some cases, biomarkers might be a causal step in the path to a disease, their presence initiating or confounding the damage. In other cases, they might be a sign that the body is recovering. It can take a lot of research to figure all of this out.

6. Neurologist Juliana VanderPluym says “it is important to consider [biomarkers] as an aide, and not necessarily as the final determinant” of a diagnosis. There could be a case where an athlete reports symptoms that suggest a concussion but doesn’t show elevated levels of the biomarkers. What would you do if you were a coach or trainer faced with that situation, and why? How could scientific research help to address such cases in the future? What additional research should be completed?