The Quanundrum of Post-Concussion Syndrome

X-Ray Concussion of the BrainAlthough there is much confusion in the literature regarding what is post-concussion syndrome, a picture is beginning to emerge, which provides clarity as to our understanding of its seemingly confusing presentation.

In our latest Newsletter, “Post-Concussion Syndrome-Adults,” we present a comprehensive analysis of this subject.  The following blog article is meant only to touch on some of the aspects of this complex subject.  You can also sign up here to receive our Forensic Science Newsletter by email.

Definition of Post-Concussion Syndrome (PCS)

PCS is the manifestation of symptoms following a concussion or mild traumatic brain injury (mTBI) for an extended time, usually greater than a month. Typically, these symptoms are dizziness, fatigue, insomnia, restlessness and an inability to concentrate.

General Information

Although the terms concussion and mild (minor) head injury (mTBI) tend to be used interchangeably, the traditional definition of concussion does not allow for intracranial hemorrhage, whereas mTBI does. Concussions typically have a Glasgow Coma Scale (GCS) of 14-15, whereas mild traumatic brain injurys have a GCS of 13-15. More recent neuroimaging techniques, as well as research into what is occurring at the molecular level (immunoexcitotoxicity) within the brain following a traumatic brain injury, whether mild or severe, suggest such a distinction between concussion and mild traumatic brain injury may not have the clear separation scientifically as has been suggested. Traditionally, concussions are said to have no evidence of intracranial trauma. However, more recent neuroimaging studies, such as Diffusion Tensor Imaging, have demonstrated white matter structural changes.

Pathophysiology

Historically, early Post-Concussion Syndrome symptoms have been postulated to have an organic basis (defined pathological lesion), whereas Post-Concussion Syndrome symptoms that persist beyond 3 months have a non-organic, functional basis, the foundation of which cannot be detected by existing laboratory procedures. The anatomical basis of concussions have not been clearly defined. The activation of the immune inflammatory response (immunoexcitotoxicity) may be the underlying pathophysiologic mechanism for Post-Concussion Syndrome.

In immunoexcitotoxicity, not only cannot the neurons and glia uptake the excess glutamate, but the enzymatic reaction catalyzed by glutamine synthase is also overwhelmed, which allows for excess extracellular glutamate that contributes to the genesis of immunoexcitotoxicity.

The excessive glutamate also allows for uncontrolled intracellular entry of calcium into the neuron through glutamate receptor controlled calcium channels. This uncontrolled entry of calcium into the neuron activates cell death (apoptosis) signaling pathways that lead to cell death.

The principle immune cell of the brain is the microglia.

Although there are six types of microglia, the three most important as far as the genesis of immunoexcitotoxicity are: resting (ramified), activated (non-phagocytic and phagocytic) and ameboid phagocytic microglia.

The phagocytic state of the activated microglia is the maximally immune responsive form. It is this form of microglia that has the antigen presenting, cytotoxic and inflammatory mediating signaling.

What appears to occur is because proinflammatory cytokines and excitotoxins release occurs simultaneously, a synergistic neurodegenerative process is set in motion. This synergism between immune cytokines and excitotoxic levels of glutamate, aspartate, and QULN also have similar effects on the blood brain barrier (BBB), brain vasculature, development of edema, and metabolic changes seen within traumatic brain injury.

Epidemiology

The life time incidence of single and repeated concussions is unknown but is believed to occur in several million people annually in the United States alone. The epidemiology follows a trimodal pattern over lifetime with peaks in the first few months of life, followed by adolescence, and followed by a third peak in the elderly.

Summary

The recent research into the mechanisms underlying Post-Concussion Syndrome following traumatic brain injury, including mild traumatic brain injury, have suggest the evolution within the brain of a central pathological mechanism, which involves activation of an immune inflammatory response as the primary pathophysiologic process responsible for Post-Concussion Syndrome. This inflammatory response involves a process called immunoexcitotoxicity, which plays a key role not only in Post-Concussion Syndrome but many neurodegenerative diseases including chronic traumatic encephalopathy.

A more in depth discussion of Post-Concussion Syndrome can be found in our latest Forensic Science Newsletter – Postconcussive Syndrome-Adults. You can also sign up to automatically receive our Forensic Science Newsletters.

Post-Concussion Syndrome-Adults Newsletter

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