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Post Concussion Syndrome, PTSD, and Neuro Inflammation: Is there a Link?

Injuries to the head are very common, unfortunately. From athletes of all ages, work place accidents, fender benders, and head butts from grandchildren while rough housing, I have seen all sorts of head injuries that resulted in a stereotypical constellation of symptoms in my neurology practice. 

According to the Mayo Clinic, these can include headaches, irritability, insomnia, fatigue, nausea, poor concentration, ringing in the ears or tinnitus, blurry vision, changes in smell or taste, among others. Many of these patients were ultimately diagnosed with post concussion syndrome. However, some argue there is another possible cause. PTSD, or post traumatic stress disorder, is another type of head injury, albeit without an obvious biomechanical force. It is typically thought of as more of a psychological etiology. However, there are some reports that have found neuroinflammation in both conditions. Is it post concussion syndrome, is it PTSD, or is it a combination of the two? 

Have you ever had any combination of the above symptoms without an obvious head injury? Most people think you need to hit your head violently and have some sort of loss of consciousness or alteration in mentation in order to have a concussion. However, that is not the case. Even mild head trauma or shaking without obvious contact can have significant concussion symptoms at times. This results in a jostling of the brain within the skull. Rotational type injuries are actually thought to be worse than head on collisions, in general. The mechanism of rotation can cause shearing or tearing of axons, which are the parts of the neurons in the brain that are responsible for transmitting signals from the neuron cell body to the target organ.

Post traumatic stress disorder is not thought to be caused by a physical head injury though. According to the American Psychiatric Association, PTSD is a “psychiatric disorder that can occur in people who have experienced or witnessed a traumatic event such as a natural disaster, a serious accident, a terrorist act, war/ combat, rape or other violent personal attack.”

With head injury, a cascade of cellular responses occur within minutes of injury. The nerve impulses do not get to where they are supposed to because of this cascade. The injury leads to an imbalance of ions that were previously regulated through channels and membranes within the cells, which then causes release of excitatory neurotransmitters triggering excitotoxic, neuronal depolarization. It also causes the opening of voltage-gated potassium channels resulting in extracellular accumulation of potassium. As a response, the cell membrane triggers adenosine triphosphate dependent sodium/ potassium pumps, which increase glucose metabolism causing further metabolic derangements. The increased glucose metabolism also separately contributes to further neuronal dysfunction. An additional contributing factor to cellular injury is over activation of N methyl D aspartate or NMDA receptors due to excessive release of glutamate causing calcium to accumulate in mitochondria, the workhorse or powerhouse of cells, hindering glucose metabolism and in turn hindering ATP production. This is then followed by a prolonged state of reduced glucose metabolism and reduced cerebral blood flow. This may not occur in post traumatic stress disorder due to the lack of a biomechanical force; however, it remains an area of uncertainty.

In addition to the above injury cascade, neuro inflammation also contributes to injury, which results in the symptoms of post concussion syndrome and potentially post traumatic stress disorder. With post concussion syndrome neuro inflammation, the inflammatory cascade starts with attracting neutrophils and monocytes to the site of injury within the brain in an attempt to help heal the injured brain tissue. They do so by releasing cytokines and different signaling molecules. Local microglia and astrocytes within the brain also express inflammatory mediators and release inflammatory cytokines at the site of brain injury. In the short term, this inflammatory response is thought to be neuro protective in trying to regenerate and heal the injured brain tissue. However, if exposed to neuro inflammation for prolonged periods of time, it can ultimately be detrimental to the healing process. With PTSD neuro inflammation, it is thought that chronic inflammation contributes to comorbidities. There is an impaired stress response, chronic neuro inflammation, and a dysregulated immune response that trigger symptoms or are associated with comorbidities.

Several cytokines are known to be involved in the inflammatory response within the body. Interleukin-1 is a family of 11 cytokines. Prolonged exposure to IL-1B can trigger the release of other proinflammatory cytokines, which may create a toxic inflammatory environment for neurons. Tumor necrosis factor alpha has two known receptors in the central nervous system or CNS. One is thought to be neuroprotective (TNFR-2); however, the other is detrimental to the CNS (TNFR-1). The TNFR-1 receptor ultimately triggers apoptosis or cell death within the CNS.

In addition to inflammatory cytokines, there are anti inflammatory cytokines that counteract the inflammatory response. These include Transforming Growth Factor beta and Interleukin-10. TGF beta is a negative feedback loop that is triggered by inflammatory cytokines but then in turn suppresses their production. IL-10 is thought to be neuroprotective by reducing oxygenated free radicals and decreasing inflammatory cytokine expression.

Pro inflammatory and anti inflammatory cytokines and mechanisms have contradictory effects. Neuro inflammation appears beneficial early on but the prolonged effects can be detrimental. This cascade and where and when to act needs to be further studied. If you inhibit the inflammatory response early on, you are also inhibiting the early neuro protective response. However, if you wait too long, the damage may be too much to overcome. This inflammatory response may be similar in any brain trauma, with or without biomechanical forces. More research is needed.

Treatment for post concussion syndrome and post traumatic stress disorder is somewhat still lacking. For post concussion syndrome, the mainstay of treatment is avoiding head injuries and slow reintroduction of activities. Concussions can have an additive effect, so you want to make sure you avoid further head injuries, especially during the recovery phase. Some anti inflammatory medications have been studied but unfortunately with mixed results so far. We know the inflammatory cascade has both a beneficial and a detrimental effect. Again, more research is needed. For post traumatic stress disorder, our other blog goes into further treatment options, including cognitive behavioral therapy, medications, and Intravenous (IV) ketamine infusions.

Could IV Ketamine infusions be the next treatment for post concussion syndrome? It has been studied in the possible treatment of post traumatic stress disorder and been found to be beneficial. Ketamine is a potent NMDA antagonist and anti inflammatory agent. Both NMDA activation and neuro inflammation have been implicated in the detrimental cascade involved in post concussion syndrome. Therefore, logic would suggest that IV ketamine infusions may be a beneficial treatment option. Obviously, more research is needed. But in the right circumstances and with no other viable options, what would you do?

At StrIVeMD Wellness and Ketamine, we are a team of board-certified neurologists, anesthesiologists, and functional medicine physicians that bring a comprehensive and individualized approach to health and wellness. Specializing in medical IV infusions, we offer cutting edge treatments, including IV ketamine infusions and IV vitamin infusions, for post traumatic stress disorder and, based on the above findings, maybe even post concussion syndrome. 

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