How Infections and Inflammation Reach the Brain
By Cristina McMullen, Bioenergetic Practitioner, Longevity Health Center
In Part 1, we explored how an autoimmune response can target the brain in children with PANDAS and PANS.
Now let’s go deeper.
Because understanding how inflammation reaches the brain helps explain why some children spiral into chronic symptoms — and why others recover.
When Inflammation Doesn’t Turn Off
In a healthy immune response, inflammation is temporary.
A pathogen enters. The immune system responds.
The invader is eliminated. The immune system quiets.
But in autoimmune states, that final step fails.
Macrophages and other immune cells continue releasing inflammatory cytokines. Antibodies remain active. The immune system stays on high alert.
This prolonged immune activation doesn’t just circulate in the bloodstream — it affects barriers designed to protect vital organs.
One of the most important of those barriers is the blood–brain barrier (BBB).
The Blood–Brain Barrier: The Brain’s Security System
The blood–brain barrier is a tightly woven network of capillaries that separates circulating blood from brain tissue.
Under normal circumstances, it prevents bacteria, viruses, large proteins, and circulating antibodies from entering the brain.
But during systemic inflammation, those tight junctions can loosen.
Cytokines increase vascular permeability. Capillaries expand. The barrier becomes more permeable than it should be.
This is where autoimmune conditions become neurological conditions.
When neuroactive antibodies cross into brain tissue, they don’t behave passively. They bind. They signal. They alter neurotransmitter activity.
In PANDAS and PANS, the region most consistently implicated is the basal ganglia.
The Basal Ganglia: Where Movement, Emotion, and Habit Intersect
The basal ganglia are not a single structure but a network of nuclei located deep within the brain. They include:
The caudate nucleus
The putamen
The globus pallidus
The substantia nigra
The subthalamic nucleus
Each region contributes to coordination between movement, cognition, motivation, and emotion.
The caudate nucleus, for example, plays a role in inhibitory control and procedural learning. The putamen influences movement patterns and habit formation. The substantia nigra helps regulate dopamine — a neurotransmitter central to reward and motor control.
When inflammation affects this network, the results can be profound:
Repetitive motor movements
Intrusive thoughts
Compulsive behaviors
Emotional volatility
Impulsivity
Sensory dysregulation
Imaging studies during acute PANDAS episodes have demonstrated enlargement of the caudate and putamen. In some documented PANS cases associated with Lyme neuroborreliosis, MRI findings have even shown infarction within basal ganglia structures.
These are not subtle findings.
They underscore an important reality: this is not “bad behavior.” This is inflamed neural circuitry.
Beyond Strep: Other Triggers of PANS
While PANDAS is specifically associated with Group A Streptococcus, PANS expands the list of potential triggers.
Let’s walk through some of the most commonly investigated.
Epstein–Barr Virus (EBV)
EBV is incredibly common. Many children are exposed to it early in life.
Testing typically includes:
VCA IgM (indicating recent infection)
VCA IgG (which persists long term)
EBNA antibodies (which appear later)
Early Antigen (EA) antibodies (which may suggest active infection)
Interpreting EBV labs can be complex. Some antibodies remain positive for life, making it difficult to distinguish past from current activity.
Mycoplasma pneumoniae
Mycoplasma is unique among bacteria because it lacks a cell wall. That makes it harder to detect and treat.
Testing may involve:
IgM and IgG antibody levels
PCR assays that detect bacterial DNA
Because Mycoplasma can be small and elusive, false negatives are possible.
Lyme Disease and Coinfections
Lyme disease, caused by Borrelia burgdorferi, is typically evaluated using ELISA followed by Western Blot testing.
However, both tests have limitations. False negatives are common, especially early in infection. PCR testing may detect bacterial DNA, but even that depends on where the sample is drawn.
When neurological symptoms overlap with immune dysregulation, Lyme and coinfections often enter the differential diagnosis.
Environmental Factors: Metals and Mold
Heavy metals such as lead, mercury, aluminum, and arsenic can be measured through blood, urine, or hair analysis.
Mold exposure may be evaluated through antibody testing or organic acid testing. However, mold mycotoxin testing can yield false negatives if the body is not actively excreting toxins at the time of testing.
These environmental contributors don’t directly “cause” PANS in most cases. But they may increase inflammatory burden, lower immune resilience, and contribute to chronic immune activation.
Why False Negatives Are So Common
One of the most frustrating aspects of PANDAS and PANS is that testing is imperfect.
Strep titers (ASO and Anti-DNase B) don’t always rise significantly. In fact, studies have shown that only about half of confirmed strep infections produce a significant increase in ASO titers.
Timing matters. Age matters. Individual immune response variability matters.
This diagnostic uncertainty is part of why controversy persists.
