As mentioned in our previous article, in PANS/PANDAS, a bacterial or viral infection, such as strep or mycoplasma pneumonia, triggers a misdirected immune response that causes inflammation in the brain. This misdirected immune response can be devastating for the child and family, as the child may have symptoms, such as aggression, extreme anxiety, OCD, and tics.

But why do some children experience this misdirected immune response while others do not with the same infections? Though research for PANS/PANDAS is in its early stages, we address potential causes of the immune system going awry in PANS/PANDAS in this article.

Blood-Brain Barrier

Researchers suspect that there is a level of genetic susceptibility to these conditions (1). There is also concern about pathogens making their way into a child’s brain if there is a blood-brain barrier breach. The blood-brain barrier (BBB) is the network of blood vessels of the central nervous system. These vessels strictly regulate the passage of ions, molecules, and cells between the blood and the brain. When they are able to work appropriately, they also protect neural tissues from pathogens and toxins (2).

The idea that there was a BBB was created in 1906 after the observation that a large-molecular-weight dye that was put into the body through intravenous injection stained nearly all of the tissues and organs except for the brain. However, when the same dye was directly delivered to the cerebrospinal fluid in the brain ventricles, it exclusively stained the brain. Years later, with advances in electron microscopic technology, we began to see the tight junctions between cerebral capillary endothelia, which showed the structure of the BBB and how it protects the brain. (3)

Potential Causes of Blood-Brain Barrier Breach

There are a number of things that can cause a blood-brain barrier breach, which could potentially set up an environment for PANS/PANDAS (as well as other neurological conditions).

Traumatic Brain Injury: Trauma to the head can breach the blood-brain barrier. Traumatic brain injury can result in microanotomical and functional changes at the cellular level, which can compromise the tight junctions of the blood-brain barrier. This creates “leakiness,” which then allows toxic compounds to pass through. These functional changes from head injuries can cause PANS/PANDAS as well as cause relapses of the conditions. (4)

EMF Exposure: Electric and magnetic fields (EMFs) from cell phones, smart meters, large electrical devices, WiFi, ultrasounds, and baby monitors are hard to avoid in this day and age. However, it’s important to be mindful of our exposure to them, as some researchers suspect they also cause a breach in the blood-brain barrier (5). In a 2015 study with rats, researchers found that a 28 day EMF exposure caused cellular edema (accumulation of excess fluid), neuronal cell degeneration, and damaged blood-brain barrier permeability. Though many have considered the limited available research data inconclusive on humans, scientists feel that we need further research on the topic (6). There is also a lot of anecdotal evidence showing neurological and systemic symptoms following increased EMF exposure through WiFi (7) or Smart Meter installation (8).

Gut dysbiosis: Because the microbiome contributes to BBB integrity, gut health is extremely important for brain health. In one particular study, mice with abnormal gut flora had increased BBB permeability as compared to the mice with the normal flora. Interestingly (and optimistically), when the mice with abnormal flora were exposed to the mice with normal flora, their BBB permeability was decreased. (9) Exposure to antibiotics or continuous exposure to inflammatory foods can compromise the gut and subsequently, the BBB.

Photo by Mark Fletcher-Brown on Unsplash

Toxin Exposure: Toxins can also compromise the integrity of the BBB. Toxic metals, such as aluminum and lead, are shown to alter the barrier function. Exposure to aluminum in animal studies has resulted in the degeneration of cerebral neurons. Exposure to lead also inhibits the production of transthyretin in the blood-cerebrospinal spinal fluid barrier, which is essential to transporting thyroid hormone in the brain. (10)

Mycotoxins are also a factor in BBB dysfunction. Research has found structural abnormalities in the brains of those with chronic inflammatory response syndrome (CIRS), or “mold illness,” following exposure to water-damaged buildings. (11)

Pesticides may also be toxins that contribute to BBB dysfunction. Animal studies have also shown BBB dysfunction after exposure to specific pesticides (12), especially exposure in early development (13).

Inflammation: Both high-grade systemic inflammation and low-grade systemic inflammation can increase the permeability of the BBB. Examples of high-grade systemic inflammation are meningitis, encephalitis, sepsis, and local and systemic infections, such as infections contributing to PANS/PANDAS (14, 15). While examples of low-grade systemic inflammation include metabolic syndrome, insulin resistance, type 2 diabetes, arterial hypertension, and obesity (16, 17, 18, 19).

The factors listed above (traumatic brain injury, EMF exposure, gut dysbiosis, toxin exposure) can also contribute to systemic inflammation. Oftentimes, there is not just one cause, but many that contribute to inflammation, BBB disruption, and a compromised immune system.

Examples of BBB disruption:

Specific examples of the BBB disruption that can occur are:

Modification of tight junctions- Inflammation can loosen the tight junctions of the BBB, increasing permeability.
Endothelial damage- Damage can include endothelial apoptosis, membrane abnormalities, and mitochondrial damage. This damage contributes to barrier dysfunction.
Degradation of glycocalyx- The glycocalyx is the structure that lines the endothelium. Evidence shows that a continuous glycocalyx is important to BBB function, and that degradation of glycocalyx can lead to permeability of the BBB.
Breakdown of glia limitans- The glia limitans is the innermost layer of the BBB. Systemic inflammation can break down this layer.
Astrocyte changes- Astrocytes maintain the BBB, and astrocyte destruction results in BBB disruption. (20)

When the BBB is breached or disrupted, this allows infections to go to the brain and wreak havoc. A comprehensive look at the patient is needed for complete healing.

While it is heartbreaking to watch your child suffer, there is hope! Please look for our next article on treating PANS/PANDAS.

While we do not directly treat PANS/PANDAS, we look into and support adaptive physiology contributing to any root issues involved in PANS/PANDAS. We also work as a team with medical professionals who do treat PANS/PANDAS to give the best care possible. As always, please call our office with any questions about addressing root issues in your child’s health.

Works cited:

What Happened to My Child?? Part II: Potential Causes of PANS/PANDAS

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