Traumatic Brain Injury: a Chronic Disease That Affects More Than the Brain

The long-term neurological and psychiatric effects of traumatic brain injury (TBI) have been well studied and reported. Now, due in part to high-profile cases of TBI among professional athletes and military veterans, scientists and clinicians are starting to recognize links between TBI and the emergence of cardiometabolic disease.

One researcher studying these links is Saef Izzy, MD, MBChB, an associate neurologist in the Division of Critical Care Neurology at Brigham and Women’s Hospital. Dr. Izzy became interested in studying TBI as a medical student treating patients during the Iraq War in 2003, when he saw firsthand the impact of acute and chronic brain injuries.

“In addition to focusing on basic and translational science surrounding TBI, I’m keenly interested in long-term outcome studies,” Dr. Izzy says. “We are finding that TBI is not just an acute injury, but a chronic disease and multisystem condition that affects far more than just the brain. Comorbidities linked to TBI can complicate the course of recovery, increase mortality, and add to overall health care costs.”

TBI Patients May See Benefit in Disease Screening

Dr. Izzy and colleagues recently completed a prospective longitudinal cohort study (published in JAMA Network Open) of patients who experienced TBI but had no prior clinical comorbidities. Patients were followed for up to 10 years after experiencing a mild or moderate-to-severe TBI and were compared with patients without TBI.

The study found that rates of cardiovascular (hypertension, hyperlipidemia, obesity, and coronary artery disease) comorbidities and endocrine diseases, notably diabetes, after TBI were significantly higher in patients with mild or moderate to severe TBI compared with patients without TBI.

Furthermore, the risk of post-TBI comorbidities, most specifically cardiovascular comorbidities, was higher in all age groups compared with age-matched unexposed patients, particularly in patients younger than 40 years, and post-TBI comorbidities were associated with higher mortality over the 10-year follow-up period.

“These findings suggest that patients with TBI in all age groups may benefit from a proactive targeted screening program for chronic multisystem diseases, particularly cardiometabolic diseases,” Dr. Izzy says. “We also see a benefit in studying the mechanisms by which acute brain injury leads to the emergence of these chronic comorbidities.”

In the study, Dr. Izzy and his colleagues proposed mechanisms including behavioral and lifestyle changes (e.g., physical inactivity, unhealthy diet, social isolation, systemic metabolic changes) or increased propensity for other risk diseases, including sleep disorders and depression. Other possibilities include the alteration neuroinflammatory pathways post-injury.

An invited editorial in JAMA Network Open praised the significance of the study, commending its authors for “shedding light on an understudied problem” and pointing to its particular relevance in younger patients, who “may mount a more profound autonomic and inflammatory response to injury.”

Clinic-Level Support Is Crucial

According to Dr. Izzy, the links between TBI and chronic, downstream, multi-system comorbidities support the need to follow this vulnerable patient population more closely. He also suggests that screening and treatment guidelines may also need to be reviewed and revised.

“We are working to build a case here at the Brigham for supporting our TBI patients with a clinic system through which we will follow up with them post-discharge, screen them regularly for the emergence of comorbidities, and connect them to the multidisciplinary services they need,” he says. “We believe a well-organized and properly funded clinic system through which patients receive timely treatment will improve outcomes and help reduce health costs.”

The Right Environment for TBI Research

Dr. Izzy continues to study the effects and pathways involved with TBI through several studies. In one study being conducted in collaboration with the Spaulding Brain Injury Center, he is investigating the effects of a salt-heavy diet on TBI outcomes. In another study, he is testing nasal anti-CD3 medications to see how they may modulate resident immune cells in the brain to reduce brain edema and lesion volume and improve behavioral health problems in patients with TBI.

“I started my research group to study neuroinflammation in acute brain injury,” Dr. Izzy says. “I hope to build on the significant success of the translational scientists and world-renowned researchers here at the Brigham who have been studying the role of inflammatory response in autoimmune diseases and chronic degenerative disease. My work would not be possible without the right environment, the support of the Department of Neurology, and a well-established record in advanced neuroimmunology research—all of which we have here at the Brigham.

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