Written by: Caleb Greer, Clinical Intern (CHC)
Reviewed by: Dr. Brandon Brock, MSN, BSN, RN, NP-C, DCN, DCM, DAAIM, BCIM, DACNB, FICC (Lead Clinician)
Structural content edited by: Tara Brock
Concussion: What Is It?
From high school athletes and soccer moms getting in accidents, to service men and women incurring blast impacts from IED’s, concussions and traumatic brain injuries seem to be getting a lot of attention. The story is complex and multifaceted, and here it will begin with trauma that induces rotational or linear stress on the brain. In this situation, the cerebrum gets tossed around while the brainstem undergoes shearing and more torsional-like forces. These impacts cause focal and diffuse neuronal damage that results in a complicated series of metabolic, neurologic, and immunologic consequences that I am going to cover in this paper.
Damage to neurons and stretching of axons causes what’s called mechanoporation and leads to a massive efflux of intracellular potassium, which dramatically alters ionic composition and triggers widespread depolarization and axonal swelling. As the cells depolarize, potassium is released due to the voltage-gated channels that line the neurons. The Na+/K+ pumps kick into overdrive in order to try and reestablish ionic gradients, but this processes forces the cells to go into glycolytic double time because so much ATP is needed. All of this glycolysis results in a ton of lactate that, under normal circumstances, would be shuttled on over to the mitochondria – but there is an issue with that as well. In the initial wave of depolarization, there is an enormous release of excitatory glutamate that leads to even more depolarization via AMPA, Kainite, and NMDA receptors. As NMDA receptors become activated, calcium begins to flood into cells and activate all sorts of intracellular machinery that is responsible for things such as phosphorylation of proteins, activation of phospholipases, nitric oxide synthases, endonucleases, etc. Well, when calcium concentrations are chronically high then all of these processes become overactive and result in inflammation, membrane dysfunction, and apoptosis. But, you may ask, isn’t there a compensatory mechanism for a situation like this? Absolutely! However, it’s not exactly the best trick in the magician’s hat. The mitochondria begin to sequester all the excess calcium, but the downside is that it impairs oxidative metabolism and the ability to utilize the TCA cycle – so back to all that lactate that was being produced – the risk for cerebral acidosis becomes higher and higher as the increased need for ATP stays present so long as the redox potential of the mitochondria is suffering, otherwise the lactate would actually be beneficial as a compensatory energy route. If the scenario wasn’t bad enough, research shows that cerebral blood flow decreases by up to 50%, with the duration depending on severity, which means that the tightly coupled cerebral glucose-to-perfusion ratio gets inverted and you end up with neurons that can’t function because they have no glucose and they can’t metabolize lactate. Now, it’s important to note that neurons will not be phagocytized or declare apoptosis just due to a lack of optimal function – in a normal, healthy person, compensatory mechanisms will clear up the damage, resolve inflammation, and fix the ionic disturbances. This is why, in the literature, single mild concussive events are not defined by vast neuronal death; there is actually very little, but that is not to say that there isn’t significant damage done – they also do not take into account the crazy amount of sub-concussive injuries that people incur during their life preceding an event that results in actual concussive symptoms. When someone gets whacked in the head, concussive or sub-concussive, there is an immediate increase in permeability of the blood brain barrier due to things like the ion concentration disruption and free-radical damage, which results in immediate and delayed pathological responses. Blood leukocytes see the new territory to explore and go Lewis and Clark all over it. They enter the CNS initially due to the breached barrier, but upon recognition of inflammatory cytokines released from injured tissue there becomes an actual call to arms. Hence, another character in the story is revealed – cytokine release by damaged cells. Interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNFα), and interleukin-6 (IL-6) are all released upon insult and contribute to massive inflammation and damage when they go unchecked. As neutrophils migrate through the vasculature, the cytokines bind to receptors on them and cause degranulation, which results in release of matrix metalloproteinases and other proteases that destroy the tight junction proteins that ensure the blood brain barrier’s integrity, thus perpetuating the initial immunological breach. Keep in mind that this process happens even with sub-concussive impacts, so even though little Bobbie feels all right after falling off his skateboard, he has, in reality, unleashed a neurochemical cascade that is predisposing him to future incidences. With the BBB breached and cytokines running amuck, antigen-presenting cells get tag happy and begin nibbling all kinds of new auto-antigens. As this happens, the chances of the immune system making a mistake and cross-reacting with “self” tissues get significantly higher; consequently, these people become in jeopardy of developing debilitating CNS autoimmunity.
Okay, so far we’ve covered a majority of the metabolic and immunologic aspects of concussion, and now we will move onto the neurological component. When the brain is shuffled around in the brain there are two really important anatomical things to consider: the pituitary gland and infundibulum sitting in the sella turcia, and the compact, lightweight brainstem and thalamus that sort of anchor the cerebrum. Force from any direction causes some friction between the pituitary stalk and the seat it sits in, which can damage the highway that carries impulses from the hypothalamus to the pituitary gland. This can result in hormonal changes due to the impaired delivery of hypothalamic messages to the stimulating hormone releasing centers. I could go on for days about the downstream effects of this, but that is for another time.
The key takeaway from this is that concussion can absolutely affect the endocrine system from the top down and that this is a perfect reason to run labs to rule out possible pituitary damage. The second anatomical consideration is regarding the position and susceptibility of the brainstem when the big mass it’s connected to is forcefully accelerated and decelerated. The brainstem is very vulnerable to shearing forces, which is usually what occurs during the course of a concussive injury. This is where knowing your neuroanatomy really comes in handy, as much of the symptomatology that arises from a concussive injury is region specific. For example, if you get a patient that has light sensitivity, sound sensitivity, poor pupillary responses, and terrible vertical eye movements you should automatically know that this person has some mesencephalic issues. In the same way, if you come across a patient that gets dizzy, suffers from balance problems, has bad horizontal eye movement, and has abnormal fluctuations in vitals for no apparent reason then it would reasonable to consider a pontomedullary lesion. Cortical functioning also diminishes regionally based on vector of the force and the coup– countercoup phenomenon. This is where you begin to see the classical hemispheristic changes and signs that correlate with their functional areas.
So, here is an outline of some clinical findings that may indicate a particular structure in symptomatology.
a. Frontal Lobe Function
i. Changes in Smell
ii. Poor Decision Making
iii. Personality Changes
iv. Difficulty Concentrating
v. Speech Problems
vi. Increased Saccadic Latency
vii. Brain Fog
b. Temporal Lobe/Hippocampus
i. Memory Problems
ii. Auditory Processing Issues
iii. Seizures iv. Amnesia
c. Parietal Lobe
i. Poor Somatosensory Recognition
ii. Decreased Spatial Awareness
iii. Diminished Joint Position Sense
d. Basal Nuclei
i. Changes in Emotionality
ii. Thought Perseveration
iii. Involuntary Movement
e. HPA
i. Abnormal Levels of Cortical Releasing Hormones
ii. Abnormal Levels of Pituitary Stimulating Hormones
f. Mesencephalic Function
i. Light Sensitivity
ii. Sound Sensitivity
iii. Vertical Eye Movements
iv. Dopaminergic Transmission v. Sympathetic Escape and IML windup
g. Pontomedullary Function
i. Vestibular Dysfunction
ii. Parasympathetic and PMRF Dampening
iii. Gag Reflex and Palatal Elevation
iv. Taste
v. Vasomotor Tone
References
- Alluri, H., Wiggins-Dohlvik, K., Davis, M., Huang, J., & Tharakan, B. (2015). Blood–brain barrier dysfunction following traumatic brain injury. Metabolic Brain Disease, 30(5), 1093-1104. http://dx.doi.org/10.1007/s11011-015-9651-7
- Borich, M., Cheung, K., Jones, P., Khramova, V., Gavrailoff, L., Boyd, L., & Virji-Babul, N. (2013). Concussion. Journal Of Neurologic Physical Therapy, 37(3), 133-139. http://dx.doi.org/10.1097/npt.0b013e31829f7460
- Brosseau-Lachaine, O., Gagnon, I., Forget, R., & Faubert, J. (2008). Mild traumatic brain injury induces prolonged visual processing deficits in children. Brain Inj, 22(9), 657-668. http://dx.doi.org/10.1080/02699050802203353
- Giza, C., & Hovda, D. (2014). The New Neurometabolic Cascade of Concussion. Neurosurgery, 75, S24- S33. http://dx.doi.org/10.1227/neu.0000000000000505
- Khuman, J., Meehan, W., Zhu, X., Qiu, J., Hoffmann, U., & Zhang, J. et al. (2010). Tumor necrosis factor alpha and Fas receptor contribute to cognitive deficits independent of cell death after concussive traumatic brain injury in mice. Journal Of Cerebral Blood Flow & Metabolism, 31(2), 778-789. http://dx.doi.org/10.1038/jcbfm.2010.172
- MacFarlane, M., & Glenn, T. (2015). Neurochemical cascade of concussion. Brain Injury, 29(2), 139-153. http://dx.doi.org/10.3109/02699052.2014.965208
