Understanding Post-Concussive Syndrome and Nutritional Support for Recovery

If you've had a head injury and are experiencing a new onset of lingering symptoms, you might be dealing with post-concussion syndrome (PCS). This blog article aims to help you understand the pathologic mechanisms of PCS and how nutritional approaches can aid your recovery.

Understanding Post-Concussive Syndrome

Before diving into the topic of PCS, let's first understand a little bit about traumatic brain injury (TBI). TBI is an umbrella term for any injury to the brain caused by external forces, such as blows to the head, falls, car accidents, and sports injuries.

A concussion is a mild form of TBI that occurs when the brain trauma disrupts normal neurofunction, leading to a temporary alteration in mental status or consciousness. Concussion symptoms can manifest as headaches, confusion, dizziness, nausea, balance problems, memory disturbances, and mood changes. Any of these symptoms typically arise immediately or within a few hours after the incident and generally resolve within a few days to a few weeks with appropriate rest and care.

The name of PCS tells us a lot about its nature: a complex, chronic, and progressive brain disorder with continuous and exacerbated symptoms of the original concussion. PCS can persist for a prolonged period after the initial concussion, often beyond three months. There is a wide array of PCS clinical characteristics, including headaches, dizziness, fatigue, irritability, anxiety, depression, insomnia, difficulty concentrating, memory dysfunction, tinnitus, visual disturbances, and sensitivity to light and noise. These debilitating symptoms can significantly impact the overall quality of life.

It is crucial to keep in mind that not everyone who suffers from a concussion ends up with PCS. The prevalence rate of PCS in patients with concussion has been documented as 25-30% (van der Vlegel et al., 2021). While the management of concussion generally focuses on rest and gradual return to activities, PCS requires a more comprehensive approach, often involving symptom management, rehabilitation, and psychological support.

In summary, a concussion is a temporary brain function disruption following a concussion, whereas PCS is a chronic condition where symptoms persist long after the initial concussion.

The Main Pathologic Mechanisms of PCS

The pathologic mechanisms of PCS are often multifactorial, encompassing a combination of the following physical, chemical, and psychological aberrations in the brain:

Structural Damage: During a concussion, the brain's nerve fibers (axons) can be stretched or torn, leading to a loss of structural integrity and/or axonal disconnection, disrupting normal brain signaling. Also, microstructural injury in the brain's white matter, which may not be evident on CT or MRI scans, can occur (Giza & Hovda, 2014).

Neurochemical and Metabolic Changes: Concussions can result in ionic flux, changes in cerebral blood flow, and a surge in glutamate release, an excitatory neurotransmitter. These changes trigger a cascade of events, including the ionic flux, which induces a diffuse depressive state, glutamate elevation leading to neurotoxicity with neuron-damaging effects, and changes in cerebral blood flow, causing cognitive and emotional symptoms. Furthermore, the brain's energy demand shifts to overdrive following a concussion, while its ability to produce energy is impaired by altered glucose metabolism. This metabolic mismatch can contribute to ongoing symptoms (Giza & Hovda, 2014).

Neuroinflammation: Inflammatory responses to a concussion involving the activation and infiltration of the brain's glial cells can persist for a long time. Prolonged inflammation can impair neural repair processes and contribute to PCS symptoms. Elevated levels of pro-inflammatory cytokines and chemokines have been observed in PCS, indicating an ongoing inflammatory response (Giza & Hovda, 2014).

Blood-Brain Barrier (BBB) Disruption: Concussions, especially repeated ones, can cause structural changes in the BBB. This may increase BBB permeability, potentially allowing harmful substances to enter the central nervous system and exacerbating neuroinflammation and neuronal damage (Sahyouni et al., 2017).

Psychological Impact: Anxiety and depression often follow a concussion episode. Individuals with a history of anxiety may be more susceptible to developing PCS or more significant PCS symptoms, especially among adolescents and young adults. Elevated post-concussion anxiety can be the strongest predictor of persistent PCS (Iverson et al., 2021).

Autonomic Nervous System (ANS) Dysregulation: One aspect of concussion neuropathology is PCS's potential to contribute to ANS anomalies, thereby altering heart rate, blood pressure, and other bodily functions (Pertab et al., 2018).

Hypothalamic-Pituitary Axis (HPA) Dysfunction: A concussion can significantly impact the HPA, leading to substantial endocrine disturbances and subsequent hormonal imbalances that affect mood, energy levels, and overall brain function (Javed et al., 2015).

Nutritional Support for Post-Concussive Syndrome

Currently, there is a significant gap in the standard treatment options for PCS, let alone their side effects. Given PCS's complex pathophysiology, a one-size-fits-all, symptom-focused "Band-Aid" approach is likely insufficient to achieve desirable clinical outcomes. Therefore, there is much need to explore novel, safe, and natural therapeutic options.

Nutraceutical Considerations:

Depending on the clinical presentation, specific nutraceutical agents can be considered to improve PCS symptoms and patients' quality of life by targeting the underlying pathologic mechanisms of PCS, as elucidated earlier. Here are a couple of examples:

Honokiol:

Honokiol is a bioactive compound extracted from the bark and leaves of the magnolia tree. Amazingly, honokiol can easily cross the BBB, thereby increasing its accessibility to neuronal tissues and exerting its neuroprotective effects through various mechanisms (Woodbury et al., 2013).

As a powerful antioxidant, honokiol can reduce oxidative stress on brain cells. It has been shown to inhibit programmed cell death in neurons, a critical mechanism in protecting brain cells after a TBI. Honokiol also has potent anti-inflammatory properties that can mitigate neuroinflammation, alleviating PCS-associated symptoms such as headaches, cognitive impairment, and mood disturbances.

Moreover, Honokiol may promote the formation of new neurons and synaptic plasticity, which is crucial for cognitive recovery after brain injury. Last but not least, honokiol has been shown to have anxiolytic and antidepressant effects on modulating the activity of GABA receptors in the brain, which play a crucial role in regulating mood and anxiety (Faysal et al., 2023).

CDP-Choline:

CDP-choline (or Citicoline) is an endogenous compound critical in synthesizing phospholipids and other essential components of cell membranes. It is a precursor to acetylcholine, a crucial neurotransmitter for cognitive function. CDP-choline has excellent therapeutic potential for individuals with PCS due to its multiple mechanisms of action.

Because CDP-choline plays a crucial role in upregulating acetylcholine, CDP-choline supplementation may improve cognitive symptoms induced by PCS. It is also involved in the biosynthesis of phosphatidylcholine, an essential phospholipid in maintaining cell membrane integrity and function (Choline—Nutrition and Traumatic Brain Injury—NCBI Bookshelf, n.d.).

Moreover, CDP-choline's antioxidant effects may reduce the neuronal damage from oxidative stress induced by a mTBI, thereby aiding recovery. Research has also shown that CDP-choline can reduce programmed cell death in neurons, protecting against further neuronal loss after brain injury (Choline - Nutrition and Traumatic Brain Injury - NCBI Bookshelf, n.d.). Furthermore, like honokiol, CDP-choline has been shown to reduce neuroinflammation and support energy production in the brain cells (Secades & Gareri, 2022).

Dietary Consideration

The ketogenic diet (KD) is characterized by high-fat, moderate-protein, and low-carbohydrate intake. It offers several potential mechanisms that could benefit individuals suffering from PCS.

First, as discussed earlier, TBI can impair glucose metabolism in the brain. By inducing ketosis, the KD shifts the body and brain into a metabolic state in which ketone bodies become the primary energy supply rather than glucose, providing a stable energy supply to the brain.

Additionally, KDs are believed to reduce oxidative stress, regulate neurotransmitter balance, increase brain-derived neurotrophic factor levels, and stabilize blood sugar levels, all of which are crucial for recovery from brain injuries (Altayyar et al., 2022). Even though more research is still needed, evidence has shown that KD may be a novel, effective approach to increasing the brain’s resistance to damage and has therapeutic potential as a TBI treatment (Har-Even et al., 2021; Rippee et al., 2020).

Lastly, as a reminder, it is vital to approach the KD carefully. Its implementation should be guided and monitored by a ketogenic nutrition specialist to personalize the diet and ensure its safety and efficacy.

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References:

• Giza, C. C., & Hovda, D. A. (2014). The New Neurometabolic Cascade of Concussion. Neurosurgery, 75(0 4), S24. https://doi.org/10.1227/NEU.0000000000000505 Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479139/ 

• Sahyouni, R., Gutierrez, P., Gold, E., Robertson, R. T., & Cummings, B. J. (2017). Effects of concussion on the blood–brain barrier in humans and rodents. Journal of Concussion, 1, 205970021668451. https://doi.org/10.1177/2059700216684518

• Pertab, J. L., Merkley, T. L., Cramond, A. J., Cramond, K., Paxton, H., & Wu, T. (2018). Concussion and the autonomic nervous system: An introduction to the field and the results of a systematic review. Neurorehabilitation, 42(4), 397. https://doi.org/10.3233/NRE-172298 

• Javed, Z., Qamar, U., & Sathyapalan, T. (2015). Pituitary and/or hypothalamic dysfunction following moderate to severe traumatic brain injury: Current perspectives. Indian Journal of Endocrinology and Metabolism, 19(6), 753. https://doi.org/10.4103/2230-8210.167561 

• Iverson, G. L., Greenberg, J., & Cook, N. E. (2021). Anxiety Is Associated With Diverse Physical and Cognitive Symptoms in Youth Presenting to a Multidisciplinary Concussion Clinic. Frontiers in Neurology, 12, 811462. https://doi.org/10.3389/FNEUR.2021.811462 

• Faysal, M., Khan, J., Zehravi, M., Nath, N., Singh, L. P., Kakkar, S., Perusomula, R., Khan, P. A., Nainu, F., Asiri, M., Khan, S. L., Das, R., Emran, T. Bin, & Wilairatana, P. (2023). Neuropharmacological potential of honokiol and its derivatives from Chinese herb Magnolia species: understandings from therapeutic viewpoint. Chinese Medicine 2023 18:1, 18(1), 1–22. https://doi.org/10.1186/S13020-023-00846-1 

• Woodbury, A., Yu, S. P., Wei, L., & García, P. (2013). Neuro-Modulating Effects of Honokiol: A Review. Frontiers in Neurology, 4. https://doi.org/10.3389/FNEUR.2013.00130 

• Secades, J. J., & Gareri, P. (2022). Citicoline: pharmacological and clinical review, 2022 update. Revista de Neurología, 75(Supl 5), S1. https://doi.org/10.33588/RN.75S05.2022311 

• Choline - Nutrition and Traumatic Brain Injury - NCBI Bookshelf. (n.d.). Retrieved July 30, 2024, from https://www.ncbi.nlm.nih.gov/books/NBK209327/ 

• Altayyar, M., Nasser, J. A., Thomopoulos, D., & Bruneau, M. (2022). The Implication of Physiological Ketosis on The Cognitive Brain: A Narrative Review. Nutrients, 14(3). https://doi.org/10.3390/NU14030513 

• Har-Even, M., Rubovitch, V., Ratliff, W. A., Richmond-Hacham, B., Citron, B. A., & Pick, C. G. (2021). Ketogenic Diet as a potential treatment for traumatic brain injury in mice. Scientific Reports 2021 11:1, 11(1), 1–12. https://doi.org/10.1038/s41598-021-02849-0 

• Rippee, M. A., Chen, J., & Taylor, M. K. (2020). The Ketogenic Diet in the Treatment of Post-concussion Syndrome—A Feasibility Study. Frontiers in Nutrition, 7, 160. https://doi.org/10.3389/FNUT.2020.00160/FULL Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511571/ 

• van der Vlegel, M., Polinder, S., Toet, H., Panneman, M. J. M., & Haagsma, J. A. (2021). Prevalence of Post-Concussion-Like Symptoms in the General Injury Population and the Association with Health-Related Quality of Life, Health Care Use, and Return to Work. Journal of Clinical Medicine, 10(4), 1–18. https://doi.org/10.3390/JCM10040806