Brain Injury Is a Chronic Health Condition

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In 2010, Doug DeWitt and I published a paper in the Journal of Neurotrauma titled “Traumatic Brain Injury: A Disease Process, Not an Event.”¹ In 2013, John D. Corrigan and Flora M. Hammond published “Traumatic Brain Injury as a Chronic Health Condition” in the Archives of Physical Medicine and Rehabilitation.² These 2 papers promoted the concept that a brain injury was not a static issue, but rather, a brain injury was disease causative and disease accelerative. We believe these papers were a catalyst that moved the research field beyond just looking at the acute effects of a brain injury.

Now, 15 years later, the Center for Medicare and Medicaid Services (CMS) has recognized brain injury as a chronic health condition, defined as “a condition that lasts one year or more and requires ongoing medical attention and/or limits activities of daily living.”³ This is a major win for our field, as we feel this will result in better resources for brain injury research and treatment, not only from governmental sources but also from private insurers as well. Just as a brain injury is not static, our discoveries about brain injury over the past 15 years have significantly advanced.

Mortality

While we have known for more than 20 years that individuals with moderate-severe traumatic brain injuries (TBIs) have a life expectancy reduction of approximately 7 years,⁴ we are now aware that individuals with mild TBI have a reduction in life expectancy with a 47% increase in 5-year mortality and an increased incidence of death from neurodegenerative disease.⁵

Neurodegenerative Disease

We are now acutely aware that a TBI may cause or accelerate neurodegenerative disease. A large study of veterans with both civilian-type and combat-related rate injuries showed a significant increase in the chance of dementia with rising risk associated with increasing TBI severity.^6,7

Parkinson Disease

The connection between a history of TBI and developing Parkinson disease is well-established. In a study of more than 300,000 veterans, a mild TBI was associated with a 56% increased risk of Parkinson disease.⁸ Other authors have had similar findings.^9-11

Chronic Traumatic Encephalopathy

Although rarely discussed 20 years ago, chronic traumatic encephalopathy (CTE) has become part of American conversations on an almost daily basis. It should be noted that CTE is a pathologic diagnosis—only officially made at autopsy. The symptoms that someone may have before succumbing to CTE are referred to as traumatic encephalopathy syndrome (TES). Nevertheless, the term CTE is widely used to describe those symptoms prior to death.

Parkinsonism and subsequent dementia occur more frequently in individuals with a pathologic diagnosis of CTE.¹² In a survey of 729 participants, those with a history of playing organized football had higher odds of having Parkinson disease compared with participants in other organized sports. Longer duration and a higher level of play were associated with increased incidence of Parkinson disease.¹³

Unfortunately, the risk of developing CTE is not just limited to American football players. In a study of 152 deceased contact sports participants, CTE was diagnosed in 63% of those studies, with 60 individuals diagnosed with mild CTE. Brain donors who had CTE were more likely to be older, and 71% were men who played amateur sports; 1 woman played collegiate soccer. Cognitive and neurobehavioral symptoms are frequent among all brain donors, and suicide was the most common cause of death.¹⁴

Sleep

In a study of roughly 200,000 veterans, after adjustment for demographics, education, income, and medical and psychiatric conditions, those who had a TBI were 41% more likely to develop a sleep disorder than those who did not have a TBI.¹⁵

Etiology and Current Research

Although it will be many years until we understand the underlying mechanisms, we are making progress. An important recent discovery is that we now know that individuals with chronic TBI have significantly lower circulating concentrations of numerous amino acids, which are the building blocks of protein and brain neurotransmitters. This pattern is consistent with the concept that TBI induces a chronic state.¹⁶ Because these essential amino acids are not getting absorbed from the gut, essentially, the brain and body are starving for their nutrients.

We now believe that the chronic low amino acid levels are a result of an altered fecal micro biome (gut dysbiosis) in individuals with chronic TBI.¹⁷ These abnormalities were found to be essentially unchanged in a study at CNS that followed these individuals over 5 years.¹⁸ We are presently looking at ways of “normalizing” the microbiome. If successful, it might make a significant improvement in the quality of life for those with chronic TBI.

These studies have also given rise to a new syndrome of brain injury altered cognition and fatigue (BIAFAC). Individuals with BIAFAC will complain of profound fatigue and “brain fog” and have been found to have an abnormal gut microbiome and abnormal growth hormone secretion. Although they frequently respond clinically to growth hormone replacement, there is no change in their gut microbiome.¹⁹

The Future of Brain Injury Rehabilitation

Brain injury rehabilitation can move forward only if we are willing to adopt the latest research findings. To ensure these research findings do not become just an academic exercise, funding sources must be a part of this effort. Only then will patients receive the most cutting-edge care and get the best outcomes which they so readily deserve.

Concluding Thoughts

We have learned a great deal about TBI in the past 15 years. It is now readily accepted that a brain injury is not a static event and is disease causative as well as disease accelerative. Although we clearly have a long way to go, we are on the path to put together the many pieces of the puzzle that make up a TBI. Some day, those pieces will all come together, and we will find the cure.

Dr Masel is the executive vice-president for Medical Affairs with the Centre for Neuroskills and is a clinical professor of neurology at the University of Texas Medical Branch in Galveston.

References

1. Masel BE, DeWitt DS. Traumatic brain injury: a disease process, not an event. J Neurotrauma. 2010;27(8):1529-1540.

2. Corrigan JD, Hammond FM. Traumatic brain injury as a chronic health condition. Arch Phys Med Rehabil. 2013;94(6):1199-11201.

3. Centers for Medicare and Medicaid Services officially recognizes brain injury as a chronic condition. Brain Injury Association of America. July 31, 2024. Accessed November 15, 2024. https://www.biausa.org/public-affairs/public-awareness/news/centers-for-medicare-and-medicaid-services-officially-recognizes-brain-injury-as-a-chronic-condition

4. Harrison-Felix C, Whiteneck G, DeVivo M, et al. Mortality following rehabilitation in the Traumatic Brain Injury Model Systems of Care. NeuroRehabilitation. 2004;19(1):45-54.

5. Sercy E, Orlando A, Carrick M, et al. Long-term mortality and causes of death among patients with mild traumatic brain injury: a 5-year multicenter study. Brain Inj. 2020;34(4):556-566.

6. Barnes DE, Byers AL, Gardner RC, et al. Association of mild traumatic brain injury with and without loss of consciousness with dementia in US military veterans. JAMA Neurol. 2018;75(9):1055-1061.

7. Barnes DE, Kaup A, Kirby KA, et al. Traumatic brain injury and risk of dementia in older veterans. Neurology. 2014;83(4):312-319.

8. Gardner RC, Dams-O’Connor K, Morrissey MR, Manley GT. Geriatric traumatic brain injury: epidemiology, outcomes, knowledge gaps, and future directions. J Neurotrauma. 2018;35(7):889-906.

9. Schrag A, Bohlken J, Dammertz L, et al. Widening the spectrum of risk factors, comorbidities, and prodromal features of Parkinson disease. JAMA Neurol. 2023;80(2):161-171.

10. Nejtek VA, James RN, Salvatore MF, et al. Premature cognitive decline in specific domains found in young veterans with mTBI coincide with elder normative scores and advanced-age subjects with early-stage Parkinson's disease. PLoS One. 2021;16(11):e0258851.

11. Lee YK, Hou SW, Lee CC, et al. Increased risk of dementia in patients with mild traumatic brain injury: a nationwide cohort study. PLoS One. 2013;8(5):e62422.

12. Adams JW, Kirsch D, Calderazzo SM, et al. Substantia Nigra pathology, contact sports play, and parkinsonism in chronic traumatic encephalopathy. JAMA Neurol. 2024;81(9):916-924.

13. Bruce HJ, Tripodis Y, McClean M, et al. American football play and Parkinson disease among men. JAMA Netw Open. 2023;6(8):e2328644.

14. McKee AC, Mez J, Abdolmohammadi B, et al. Neuropathologic and clinical findings in young contact sport athletes exposed to repetitive head impacts. JAMA Neurol. 2023;80(10):1037-1050.

15. Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol. 2021;17(3):157-172.

16. Durham WJ, Foreman JP, Randolph KM, et al. Hypoaminoacidemia characterizes chronic traumatic brain injury. J Neurotrauma. 2017;34(2):385-390.

17. Urban RJ. A treatable syndrome in patients with traumatic brain injury. J Neurotrauma. 2020;37(8):1124-1125.

18. Pyles RB, Miller AL, Urban RJ, et al. The altered TBI fecal microbiome is stable and functionally distinct. Front Mol Neurosci. 2024:17:1341808.

19. Yuen F, Thirumalai A, Pham C, et al. Daily oral administration of the novel androgen 11β-MNTDC markedly suppresses serum gonadotropins in healthy men. J Clin Endocrinol Metab. 2020;105(3):e835-e847.