Blood-brain barrier dysfunction in Pediatric Acute Neuropsychiatric Syndrome (PANS) and Regulation

Dr. Jennifer Frankovich reviews what we know about the underlying mechanisms, trajectories, and symptoms of Pediatric Acute Neuropsychiatric Syndrome (PANS). She discusses the role of the Basal Ganglia in PANS symptoms and cites contemporary research that highlights this connection. Frankovich touches on the disruption of the blood-brain barrier and auto-antibody regulation in PANS. 

Playback of Dr. Mondal’s presentation and Dr. Hussein’s presentation will be available at a future date.

In this webinar:

1:30 – PANS/PANDAS overview
3:10 – Underlying mechanisms
5:00 – Common symptoms
7:55 – PANS trajectories
9:35 – Basal Ganglia
13:12 – Antibodies and the blood-brain barrier

PANS/PANDAS

Frankovich outlines Pediatric Acute Neuropsychiatric Syndrome (PANS) and Pediatric Acute Neuropsychiatric Disorders Associated with Strep (PANDAS), underscoring the different triggers attributed to both conditions (1:30). Classification criteria for both PANS and PANDAS include a sudden onset of obsessive-compulsive disorder or eating restrictions along with at least two other co-occurring conditions like anxiety, sensory dysregulation, motor abnormalities, developmental regression, and deterioration of cognitive functioning (2:15). 

Underlying mechanisms

Children with PANS-related symptoms often have some form of immune predisposition. The speaker explains that PANS occurs after a person gets an infection, which, due to predisposition, causes a systemic inflammatory response. She notes that these inflammatory responses may lead to Basal Ganglia inflammation, altered neuronal signaling, microbial activation, and more (3:10). 

Common symptoms

The presenter describes classic PANS experiences, such as swelling in the knees, hips, and heel bones, back pain and inflammation, and evidence of psoriasis. She explains that children who experience their first case between the ages of five and ten will likely have arthritis by the time they are 14 (5:00). Frankovich highlights our bodies’ abilities to self-regulate inflammation, noting that in many cases, PANS symptoms are resolved on their own (7:15). 

PANS Trajectories

There are generally four different trajectories for PANS:

• Relapsing and remitting – returning to the same baseline
• Relapsing and remitting – worsening baseline across time
• Primary persistent – no return to baseline, remains in chronic episode
• Secondary persistent – multiple episodes with increasing baseline until it reaches a chronic episode. 

Frankovich asserts that the primary and secondary persistent trajectories are likely more related to autoimmune predispositions than the others. Therefore, she continues, these trajectories require the most intense treatments and assessments (7:55). 

Basal Ganglia

The Basal Ganglia (BG), a group of nuclei located beneath the cerebral cortex, has an inhibitory influence on motor and behavior systems. The speaker notes that inflammation, autoantibodies, and injury can disrupt the BG, affecting movements, mood, emotion, behavior, procedural learning, and cognition (9:35). 

Frankovich briefly presents four brain imaging studies suggesting BG inflammation in PANS. She also discusses three studies indicating that patients experience abnormal movements during REM sleep cycles. These REM movements predict Parkinson’s in adults, making this a critical area of research and care (10:25). 

Other physical signs of BG disruption include specific tongue and mouth movements. For example, a positive glabellar tap reflex is present in children with PANS, though it should disappear after infancy. Other abnormal tongue movements, like milkmaid grip, are discussed (11:55). The speaker notes that between 80 and 92% of patients in her clinic exhibit at least one sign of BG disruption (12:25).

19% of autistic youth also have a positive glabellar tap, and 27% have milkmaid grip tongue movements. The presenter, therefore, asserts that these BG signs are not unique to PANS and should be investigated carefully across groups (12:38). 

Antibodies and the blood-brain barrier

PANS autoantibodies target interneurons and have been found in healthy kids and children with PANDAS. Frankovich explains that if these antibodies are causing problems in the body, it is because they are crossing the blood-brain barrier (BBB) (13:12). She highlights that current research suggests local disruptions to the BBB are associated with PANS symptoms (13:50).

Originally published on June 14, 2024