A word from Dr. Mark L. Gordon, AJT Holdings Group Lead Medical Director
Non-Traumatic Brain Injury or Viral Encephalopathy
Well it was anticipated and just a matter of time before the reports started appearing about the neurological impact of Covid-19 on the brain. Those of you who have been following my work on traumatic and non-traumatic brain injuries(1) are now going to be witnessing the rise of neuropsychiatric conditions in association with the coronavirus. This is the non-traumatic form of brain injury being precipitated by Covid-19 that induces a massive release of inflammatory cytokines being referred to as “Cytokine Storm” or actually Autoimmune Encephalitis(2). This is being exacerbated by a secondary viral infection of the brain or Viral Encephalitis(3).
Dr. Jennifer Frontera, a neurologist at NYU Langone Brooklyn hospital is seeing coronavirus patients with impact on the brain and nervous system. Additionally, Dr. Frontera’s team is documenting cases including seizures in COVID-19 patients with no prior history of epilepsy, and “unique” new patterns of tiny brain hemorrhages(4). In some cases, significant damage to the white matter of the brain is seen causing varied degrees of brain damage(5). A study published in the Journal of the American Medical Association last week found 36.4 percent of 214 Chinese patients had neurological symptoms ranging from loss of smell and nerve pain, to seizures and strokes(6). A paper in the New England Journal of Medicine this week examining 58 patients in Strasbourg, France found that more than half were confused or agitated, with brain imaging suggesting inflammation(7).
“We’re seeing a lot of consults of patients presenting in confusional states,” Dr. Rohan Arora, a neurologist at the Long Island Jewish Forest Hills hospital told AFP, saying that more than 40 percent of recovered Covid-19 patients exhibit altered levels of consciousness(8).
As in our veterans exposed to a spectrum of battle injuries, sports professionals on the field of play getting their “bell rung”, and civilians living and enjoying life to the fullest, there are moments of injury that are negated because they did not cause loss of consciousness, amnesia, or nausea/vomiting, but initiated a process of neuroinflammation. Neuroinflammation can be acute being associated with or without short-term neurological, cognitive, and neurobehavioral disorders(9),(10) or long-term with chronic symptomatology. As long as there is inflammation, there are Cytokines.
The Mechanisms of Damage
There are three major pathways that a virus, such as the Covid-19, can lead to neurological involvement of the brain with alterations in psychological, physiological, and physical functioning. The first, is the response of the body’s immune system directed against the invading Coronavirus. As has been seen in the elderly, those with a compromised immune systems, diabetes, multiple medical conditions and medication, there is a hyperbolic response of the immune system leading to a “Cytokine Storm”
throughout the body with the greatest impact on the respiratory system(11). It is a rapid process in many compromised individuals, moderate in some, mild in others, and in the fortunate without a missed beat. As the ability of our lungs to take in oxygen and expel carbon dioxide fails, a condition known as hypoxia looms. As hypoxia worsens, the lack of oxygen in the brain causes a loss of Fractalkine, a Chemokine that lowers the brains’ production of cytokines from the Microglia cells(5),(12). Loss of Fractalkine allows for brain derived cytokines to be released in another “Cytokine Storm”(13).
A second pathway is derived from damage to the blood brain barrier (BBB) that protects the brain from products or infections circulating below the neck. Disruption of the BBB by the presence of elevating levels of cytokines(14) produced below the neck along with those being produced by the glial cells of the brain, allows for the passage of Covid-19 into the brain to initiate a viral encephopathy(15).
The third pathway is a cumulative effect of cytokines on the molecular chemistry of the brain. Neuroinflammation leads to elevation in ROS/RNS causing a rise in the level of oxidative stress (oxidative load) which impedes the normal biochemical processes required for cell-to-cell communication(16). This can be clinically observed as a change in level of consciousness, cognition, and neuropsychobehavior(17).
As you can see from these three key pathways, they overlap in their ability to create a non-neuropermissive environment leading to the loss of neuronal and lobar functioning. If left unchecked, the ultimate effect of Covid-19 on those surviving will be a population of individuals with diminished mental and physical capacity to live independently and without medication; a scenario we see consistently at initiation of treatment with our Veteran Heroes.
Treatment
The Millennium-TBI Project has been addressing the neuroinflammation generated by traumatic and non-traumatic injuries with nutraceutical products such as eicosanoids(18), tocopherols(19), NAC(20), melatonin(21), quercetin(22), and EGCG(23), all showing their ability to lower the production of inflammatory cytokines while protecting neurons and glial cells from oxidative stress.
References:
1. Traumatic Brain Injury: A clinical approach to diagnosis and treatment. 2015. Mark L. Gordon, MD. Millennium-Phoenix
Publishing, Beverly Hills, California. 2015. ISBN: 978-0-9904630-1-6.
2. Into the Eye of the Cytokine Storm 2012. [MMBReview]
3. Neuroinfection may potentially contribute to pathophysiology and clinical manifestations of COVID-19. [Acta Physiologica]
4. Small Subset of People with COVID-19 Display Neurological Symptoms. [NY Times]
5. Chemokine CXCL10 and Coronavirus-Induced Neurologic Disease. [PUBMED]
6. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China. [JAMA]
7. Neurologic Features in Severe SARS-CoV-2 Infection. [NEJM]
8. Confusion, seizure, strokes: How COVID-19 may affect the brain. [AFP]
9. Neuroinflammation and psychiatric illness. [JNI]
10. The Role of Inflammation and microglial activation in the pathophysiology of psychiatric disorders. [NeuroScience]
11. Induction of Pro-Inflammatory Cytokines (IL-1 and IL-6) and Lung Inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): Anti-Inflammatory Strategies [PUBMED]
12. The Effects of Hypoxia and Inflammation on Synaptic Signaling in the CNS. [Neuroimmune]
13. Control of microglial neurotoxicity by the fractalkine receptor. [PUBMED]
14. Blood-brain barrier pathophysiology in traumatic brain injury. [StrokeRes]
15. Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy [Article]
16. Superoxide, peroxynitrite and oxidative/nitrative stress in inflammation. [BiochemSoc]
17. Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential
immunologic mechanisms. [PUBMED]
18. Neuroprotection for the Warrior: Dietary Supplementation with Omega-3 Fatty Acids. [PUBMED]
19. Modulation of inflammation in brain: a matter of fat. [PUBMED]
20. N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities. [PUBMED]
21. COVID-19: Melatonin as a potential adjuvant treatment. [PUBMED]
22. In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-
regulation of the NF-kB pathway. [WILEY]
23. Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives, and clinical applications. [PUBMED]
Pandemic-associated Psychological Distress
Under the influence of psychological stressors there is a spontaneous increase in microglial production of inflammatory cytokines such as IL-1, IL-1B, IL-6 and TNF-alpha. This is brought about by the downregulation of the chemokine, Fractalkine, by cortisol and corticotropin stimulating hormone. Without Fractalkine, its microglial receptors are vacant and the transcriptional trigger for inflammatory cytokines, NF-kB, is set in motion with the production of cytokines. Modulation of NF-kB’s ability to initiate translation of the cytokines is the focus of the nutraceutical components of the product Brain Care II. Available on Amazon while supplies last.
