Two studies have offered possible insights into treating mild traumatic brain injury (mTBI) – including a potential blood biomarker for injury assessment – that could shed light on the role of inflammation. They have also found evidence supporting the use of amitriptyline, historically used as an anti-depressant, but now commonly used for migraine relief, to speed up recovery.
There are currently no objective biomarkers for concussion, an invisible injury and form of mTBI, which often remains difficult to diagnose and treat. Although there are broad consensus guidelines, individual treatment decisions for this heterogeneous injury are largely left to the discretion of the physician.
Previous studies have suggested a link between C-reactive protein (CRP), an inflammatory biomarker in the blood, and TBI, but the relationship is still under-explored. Because the underlying pathophysiology remains poorly understood, it remains challenging to create a treatment plan, noted Ayse Erdemir, clinical research coordinator at HSS, and first author of both studies.
“Currently there are no established pharmacological treatments for mTBI,” Erdemir said.
Standard treatment involves physical therapy, guided exercise, and lifestyle modifications, with some options for treating headache, head pressure, and insomnia, common symptoms that can impact recovery. While previous studies of amitriptyline in this population have been inconclusive, the team’s research provides new data which may support its use in specific circumstances.
These studies, if further validated, have the potential to influence the treatment of mTBI, she said.
For the first retrospective study of 383 concussion patients, researchers focused on measurements of high sensitivity CRP (hsCRP), an inflammatory biomarker in the blood.
Erdemir said: “We found that higher levels of hsCRP were associated with more frequent reporting of symptoms like sadness and trouble falling asleep. Notably, patients with abnormal hsCRP took longer to recover compared to those with normal levels. These patients also tended to be older and have higher BMI.
“The findings suggest that hsCRP could potentially be a candidate for inclusion in biomarker panels for acute mTBI assessment, but more research is needed to understand its long-term role in tracking symptom resolution and recovery.”
The results also offer a possible new insight into the pathophysiology of the disease, suggesting that, at least in some patients, the concussion may be characterised by low levels of inflammation in the brain that resolves with tailored treatment paradigms.
For the second study, the researchers analysed data from the same group of patients, focusing on those who were prescribed amitriptyline. They found that patients who had received the drug more often had histories of depression, anxiety, and migraines, and also had more severe concussion symptoms than those who did not receive the medication. Even though their concussions appeared to be more complex and severe, patients in the amitriptyline group recovered at the same rate as more straightforward cases.
“Amitriptyline seems to play a supportive role in helping patients with more frequent and severe baseline symptoms to recover,” said Erdemir.
“A tool to treat headache and insomnia in concussion patients doesn’t just improve quality of life throughout recovery; it may also facilitate and potentially expedite recovery. Restoring normal sleep and improving sleep quality is especially important to helping the brain heal from mTBI.”
While researchers believe patients with more severe concussions are more likely to benefit, the drug may still be prescribed in other patients to relieve symptoms.
More research is clearly needed to develop clinical applications. Researchers hope to follow up by analysing longitudinal trends of hsCRP across recovery, to further support its use as a biomarker. Additional study of amitriptyline should include a randomised, controlled trial comparing the medication to placebo as well as other medications used to treat headache.
