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Traumatic Brain injury is a leading cause of morbidity in the United States. Approximately 1.4 million United States citizens suffer a traumatic brain injury each year, out of those, 80,000-90,000 will experience long term disability.(1) When checking in 5 years post-brain injury, approximately 30% of patients deteriorated in their condition; another 22% did not improve and approximately 26% managed to improve from their TBI. An unfortunate 22% lost their lives. The average life expectancy is decreased on average by 9 years, and even those fortunate enough to live, over half will be moderately or severely disabled.(2)
Sports-related concussions are a worse epidemic for our school aged children. The literature shows high school-aged football players have a higher incidence of brain injury than college-aged athletes.(3) Children who suffer brain injury, when followed up 5 years post injury, suffer from a lower performance IQ and verbal fluency when measured against control school aged children.(4) Concussions have been coined the “Silent Epidemic.”(5) A term accurately describing the lack of clinical awareness and screening for such injuries. Many clinicians simply do not have an appropriate level of understanding in determining the degree of brain injury or the knowledge in clinical management. Children affected by a traumatic brain injury may never achieve their full potential if not properly addressed. They drop out of school, adults lose their jobs and long-term depression can occur. With a lack of clinical understanding, this silent epidemic can develop into a much worse situation.
There is no excellent screening method or clinical prediction rule to determine the severity of the head injury. No clinical prediction tool is superior to the other for determining the severity of a concussion.(1) Glasgow coma scales scores less than thirteen points will result in a CT scan to determine any injury. CT can only determine any structural changes within the skull, such as edema or hemorrhage, often resulting negative. Lesions seen on brain imaging are usually associated with neurological deficit found upon clinical examination (i.e. Left-brain contusions visualized on CT scan in a patient with right hemiplegia and speech difficulty). This can result in many unnecessary tests. The common signs and symptoms of post-concussion syndrome can be found in the bar graph.
Traumatic brain injury, unchecked, can evolve into a long-term condition: Post-Concussion Syndrome. The sequela to the initial brain injury. It is characterized by symptoms lasting longer than 2-3 weeks post-incident. The typical management is a combination of NSAIDS, amitriptyline is used for headache management, sleep aid, and to manage depressive symptoms; 5-Ht can also be used along with bed rest.(6,7) A well-rounded practitioner understands the necessity of exercise medicine, nutrition support, and mind/body interventions and will incorporate this in their patient’s treatment.
Laboratory testing can further explore the traditional dietary and nutritional intervention prescriptions for the patient. The interventions used may include changes in food intake as well as supplementation with nutrients, minerals, flavonoids, or phytonutrients. Specific markers such as GFAP, SP100 or UCH-L1 markers are released into the bloodstream as early as 12-hours post injury. These markers can determine the integrity of the blood brain barrier and may assist in determining any lesion a CT may not find, but it may take up to 4 hours.(8) A physician can also order a saliva test for specific miRNA markers which correlate to the degree of damage; however, these tests are new and there is not enough evidence to support their clinical use.(9) A clinician is better off using whichever standard they are familiar with to assess a brain injury and simply beginning a well-rounded treatment trial for the patient; however, this approach is not recommended for the patient seeking care immediately after the brain injury. Thorough measures should be taken to assure there is no serious pathology such as cortical edema or hemorrhage.
Traditionally, post-concussion syndrome is thought to be the sequela to an unmanaged mTBI. The pathogenesis of such injury is assumed to be increased inflammation and free-radical damage caused by a direct trauma or coup-contra coup mechanism. Current evidence; however, shows lingering side effects from a traumatic brain injury may also be caused by the shearing of axons.(11,12)
The difference in mass between white and grey matter during the rapid movement shears the axons apart resulting in white matter axonal damage. Inertia is not our brain’s best-friend, this phenomenon has been coined diffuse axonal injury (DAI) and is most commonly found in those who experience a loss of consciousness during the injury. While post-concussion symptoms are not pathognomonic for DAI, and vice-versa, both can be found together or independent of each other.(11,12) Along with axonal damage, free radical control mechanisms suffer damage, resulting in elevated free radical production via the electron transport chain. Excess free radicals cause lipid-peroxidation to the mitochondrial membranes; thus, resulting in mitochondrial dysfunction. Mitochondrial dysfunction leads to homeostatic imbalance due to an impaired calcium buffering system. This chain of events leads to excitotoxicity and reduction of antioxidant levels, eventually oxidizing protein membrane and causing DNA fragmentation or mutation.(13,14,16)
Mechanical disruption of the Blood-Brain barrier (BBB) is also a common secondary cause of damage after a brain injury.(17) The increased oxidative stress will result in neuronal damage and delayed proper healing. This disruption is in part caused by the presence of free radicals and inflammatory markers. A pro-inflammatory response is initiated in order to repair and restore damaged cells. Neutrophils, lymphocytes, and cytokines cross the BBB resulting in M1 phenotype microglial activation. M1 phenotype microglia are proinflammatory, while M2 are anti-inflammatory. The phenotypic expression of the microglia corresponds to the presence of lipopolysaccharides and IFNγ which lead to M1 pro-inflammatory cytokine proliferation (IL-6, IL-8). An M2 Microglial phenotype is expressed when exposed to anti-inflammatory cytokines such as IL-4, IL-12 or IL-13. Thus, the M2 microglia promotes an anti-inflammatory state which can prolong the viable treatment window.(13,14)
In the presence of high inflammatory markers, astrocytes excessively lay down extracellular matrix and create barriers named glial scars. These glial scars assist in isolating inflammation to the damage tissue and create a barrier for healthy cells. Glial scars also prevent excitotoxicity by regulating extracellular glutamate levels. While they are helpful in preventing neurotoxicity, they are harmful because the chemical and physical barrier prevent damaged tissue from regenerating.(13,14) Glial scars formation can be controlled by inducing an anti-inflammatory state; thus, reducing the excess activation of astrocytes which allow a longer window of opportunity to regenerate the white matter axons. Nutrient recommendations targeted at upregulating specific metabolic pathways or to assist in rejuvenating any damaged tissue should be utilized by the examining practitioner. Often, the clinician may discover multiple condition which may be characterized by a single cause or a single condition with multiple causes.
Sources: Johnson, VE; Weber, MT; Xiao, R; Cullen, DK; Meaney, DF; Stewart, W; Smith, DH: Mechanical disruption of the blood-brain barrier following experimental concussion. Acta Neuropathologica. 2018;135(5):711-726
DynaMed Plus [Internet]. Ipswich (MA): Moderate to severe traumatic brain injury. EBSCO Information Services. Record No.T900588. Updated Nov 30, 2018. Accessed: February 2, 2019. https://www.dynamed.com.palmer.idm.oclc.org/topics/dmp~AN~T900588
Moderate to Severe Traumatic Brain Injury is a Lifelong Condition. CDC. Accessed: February 6, 2019. https://www.cdc.gov/traumaticbraininjury/pdf/Moderate_to_Severe_TBI_Lifelong-a.pdf
Halstead, ME; Walter, KD; Council on Sports Medicine and Fitness. American Academy of Pediatrics. Clinical report--sport-related concussion in children and adolescents. Pediatrics. 2010;126(3):597-615
Anderson, V; Catroppa, C; Morse, S; Haritou, F; Rosenfeld, JV: Intellectual outcome from preschool traumatic brain injury: a 5-year prospective, longitudinal study. Pediatrics. 2009;124(6):e1064-71
Traumatic brain injury, time to end the silence. Lancet Neurol. 2010;9(4):331
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FDA authorizes marketing of first blood test to aid in the evaluation of concussion in adults. Published: February 14, 2018. Accessed: February 1, 2019. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm596531.htm
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Jones, DS; Quinn, S: Reversing the Chronic Disease Trend: Six Steps to Better Wellness. The Institute for Functional Medicine. 2017. Accessed: January 16, 2019. https://p.widencdn.net/xazlwe/Intro_Functional_Medicine
Khong E, Odenwald N, Hashim E and Cusimano MD: Diffusion Tensor Imaging Findings in Post-Concussion Syndrome Patients after Mild Traumatic Brain Injury: A Systematic Review. Front. Neurol. 2016;7:156
De Rooij, R; Kuhl, E: Physical Biology of Axonal Damage. Front. Cell. Neurosci. 2018;12:144
Diego, L; Gonzales-Portillo, GS; Acosta, S; de la Pena, I; Tajiri, N; Kaneko, Y; Borlongan, CV: Neuroinflammatory responses to traumatic brain injury: etiology, clinical consequences, and therapeutic opportunities. Neuropsychiatric Disease and Treatment. 2015;11:97–106
Schimmel, SJ; Acosta, S; Lozano, D: Neuroinflammation in traumatic brain injury: A chronic response to an acute injury. Brain Circ. 2017;3:135-42
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Johnson, VE; Weber, MT; Xiao, R; Cullen, DK; Meaney, DF; Stewart, W; Smith, DH: Mechanical disruption of the blood-brain barrier following experimental concussion. Acta Neuropathologica. 2018;135(5):711-726