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 blog.

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 process 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? Well, yes, but it’s not exactly the best trick in the magician’s hat. The mitochondria begin to sequester all the excess calcium, but the downside to that is that it impairs oxidative metabolism and the ability to utilize the TCA cycle – which brings us 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 (enter ketogenesis). 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 (BBB) 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 autoantigens. 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.


When the brain is shuffled around in the skull there are two really important anatomical things to consider: the pituitary gland/infundibulum sitting in the sella turcica, and the compact, lightweight brainstem and thalamus that sort-of anchor the brain-proper. 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 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 midbrain 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 ponto-medullary lesion. Cortical functioning also diminishes regionally based on the 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:

  1. Frontal Lobe Function

  2. Changes in smell

  3. Poor decision making

  4. Personality changes

  5. Difficulty concentrating

  6. Speech problems

  7. Increased saccadic latency

  8. Brain fog

  9. ​TemporalLobe/Hippocampus

  10. Memory problems

  11. Auditory processing issues

  12. Seizures

  13. Amnesia

  14. Parietal Lobe

  15. Poor somatosensory recognition

  16. Decreased spatial awareness

  17. Diminished joint position sense

  18. Bumping into things more frequently

  19. Basal Ganglia

  20. ​Changes in emotionality

  21. Thought perseveration

  22. Involuntary movement or speech

  23. Hypothalamic-Pituitary-Adrenal-Gonadal (HPAG) Axis

  24. Cannot stay asleep

  25. Crave salt

  26. Slow starter in the morning

  27. Afternoon fatigue

  28. Dizziness when standing up quickly Afternoon headaches

  29. Headaches with exertion or stress Weak nails

  30. Cannot fall asleep

  31. Weight gain when under stress

  32. Wake up tired even after 6 or more hours of sleep

  33. Loss of libido

  34. Other hormone disturbances

  35. Mesencephalic Function

  36. Light sensitivity

  37. Sound sensitivity

  38. Vertical eye movements

  39. Dopaminergic transmission

  40. New onset anxiety

  41. Dry or excessively watery eyes/mouth

  42. Abnormally fast heart beat

  43. Pontomedullary Function

  44. Vestibular dysfunction

  45. Balance problems

  46. Digestive problems

  47. Dry or excessively watery eyes/mouth

  48. Gag reflex sensitivity and uneven palatal elevation

  49. Changes in taste

  50. Vasomotor abnormalities/headache

This list isn't comprehensive, but is instead meant to give some insight into how a concussion can manifest by brain region. If any of this sounds like you or you want to get tested for baseline neurological function give us a call! We'd love to be a part of helping you attain or maintain well-Being.