Two studies conducted by researchers at Hospital for Special Surgery (HSS) and presented at the American Academy of Neurology 2025 Annual Meeting offer fresh perspectives on the pathophysiology and treatment of mild traumatic brain injury (mTBI). The research highlights the potential usefulness of high-sensitivity C-reactive protein (hsCRP) as a blood biomarker and examines the role of amitriptyline in symptom management and recovery.
Despite the high prevalence of mTBI, the lack of objective biomarkers continues to hinder diagnosis and personalised treatment. Inflammation has long been implicated in brain injury, yet its role in mTBI remains underexplored. The first study retrospectively analysed data from 383 concussion patients, focusing on hsCRP levels. Elevated hsCRP was associated with longer recovery times, increased incidence of symptoms such as sadness and insomnia, older age, and higher BMI. These findings suggest that systemic inflammation, as indicated by hsCRP, could serve as a measurable correlate of more protracted or severe symptomatology. The authors propose hsCRP as a potential candidate for inclusion in biomarker panels for acute mTBI, pending further longitudinal validation.
The second study, using data from the same patient cohort, examined the effects of amitriptyline, a tricyclic antidepressant historically used for depression and now often prescribed for migraine. Patients who received amitriptyline tended to have more complex concussion profiles, with higher rates of comorbid depression, anxiety, and migraine, as well as more severe symptoms. Despite these complicating factors, their recovery trajectory was similar to that of patients with less severe presentations. This suggests that amitriptyline may provide tangible benefits in mTBI by alleviating symptoms that hinder recovery, particularly headache and insomnia.
Ayse Erdemir, clinical research coordinator at HSS and lead author on both studies, noted the absence of established pharmacological treatments for mTBI. Current management strategies rely on physical therapy, graded exercise, and symptom-focused interventions. The use of amitriptyline, although not universally accepted for mTBI, may represent a valuable tool in targeted symptom management. Its role in restoring sleep and reducing headache burden could be crucial in facilitating neurorecovery, particularly in patients with severe baseline symptoms.
Currently there are no established pharmacological treatments for mTBI
Ayse Erdemir
Taken together, the studies underscore the importance of understanding the inflammatory milieu in mTBI and tailoring treatment accordingly. The inclusion of hsCRP in clinical assessment protocols could help identify patients at risk of delayed recovery and guide therapeutic decisions. Similarly, selective pharmacological intervention with agents such as amitriptyline could provide symptom relief and possibly expedite recovery, especially when used as part of a broader, personalised treatment approach.
The research team advocates for future studies to further elucidate the role of hsCRP in tracking recovery and to evaluate the efficacy of amitriptyline through controlled trials.
| Read articles in ACNR’s Traumatic Brain Injury Series |
References:
High-sensitivity C-Reactive Protein (hsCRP): Retrospective Study of Potential Blood Biomarker of Inflammation in Acute Mild Traumatic Brain Injury (mTBI)
Authors: Guzide Ayse Erdemir, Niluckshi Pitigala, Joseph T. Nguyen, Teena Shetty, MD, MPhil, FAAN (HSS).
Amitriptyline for Acute Mild Traumatic Brain Injury (mTBI)
Authors: Guzide Ayse Erdemir, Niluckshi Pitigala, Joseph T. Nguyen, Teena Shetty, MD, MPhil, FAAN (HSS).
