PANDAS: A Diagnostic Conundrum

Part 2



By Kristi Wees, MSc Chemistry

Chief Patient Advocacy Officer

Empowered Medical Advocacy





Anthony L. Kovatch, MD

Pediatric Alliance — Arcadia




“Uncertainty may be uncomfortable; but blind, abject dogmatism is foolish and, sometimes, dangerous”

— Fibonacci


Above all else, clinical correlation!


If these aforementioned tests (read yesterday’s PediaBlog here) come back negative, one would assume that PANDAS/PANS has been ruled out — but one may have assumed wrong. Researchers studying PANDAS alongside the National Institute of Mental Health physician Dr.Susan Swedo (who first coined the term for this disorder) have found antibodies to neuronal receptors (located in the brain, think neurological) in the blood stream of individuals with PANDAS and PANS. You can think of these antibodies like the ones your body forms to a pathogenic bacterial invader like tuberculosis or cholera, but with one small distinction. Instead of these antibodies being formed to attack the bacterium itself, it is hypothesized that through the mechanism of “molecular mimicry” the PANDAS/PANS antibodies are attacking the host’s own cells and receptors. Take rheumatic fever as an example; this is a well-known condition where the strep bacterium triggers a “molecular mimicry” antibody attack that targets the heart and joints causing tissue damage. A similar mechanism is believed to be happening in PANDAS and PANS — this time focusing on the brain cells and receptors instead of the heart. 

A co-collaborator to Dr. Swedo at the NIMH is Dr. Madeline Cunningham, a neuro-immunology researcher who has a lab at the University of Oklahoma Health Science Center. She and her team have developed an assay that can detect the presence of some of these brain auto-antibodies (“auto” meaning “attacking self” versus attacking bacteria) to antigens in the brain. The four categories of antigens/targets this test can detect include: Dopamine D1 receptor (DRD1), Dopamine D2L receptor (DRD2L), Lysoganglioside GM1, and Tubulin. 

According to Moleculera Labs (the enterprise which developed the commercially available assay based on Dr.Cunningham’s research), “Autoimmune antibodies that bind to these targets may interfere or potentially lead to a blocking or stimulation of the function of these antigens; this, in turn, may trigger movement and neuropsychiatric disorders, along with OCD and abnormal neurologic behavior.”

Another compound that is measured on this test panel is not an antibody to a neuronal antigen, but is instead an enzyme called CamKinase, which is short for Ca2+/calmodulin-dependent protein kinase. 

Enzymes are biological molecules that act like catalysts to increase the rate of reactions  in the body.  CamKinase is an enzyme that is involved in specifically increasing activity (upregulation) of a number of neurotransmitters, including dopamine. (A short video featuring CamKinase can be viewed here.) This enzyme has also been found to play a large role in memory and learning due to its activity in the brain. (This video helps explain that discovery.)

Based on the results from these five biological markers, doctors can have more guidance on determining the root cause of their patient’s challenges. Currently, this test is not covered completely by insurance, but some families have been able to obtain partial coverage for it by working through the appeal process of their insurance company. (Moleculera Labs offers patient and physician resources regarding navigating the insurance coverage issue here.)

We are often asked if it is a requirement for a patient to have a positive Cunningham Panel result in order to receive a PANDAS or PANS diagnosis, and the answer is: “It depends on whom you ask.” Since the number of physicians diagnosing PANDAS and PANS in the local area is rather low, and since the general national consensus is that these are primarily clinical diagnoses (see more on diagnostic guidelines here ) it does not appear to be an absolute requirement. However, for those families and physicians who are looking for more data and insights into whether a child’s symptoms may be related to neuronal auto-antibodies and up-regulation of CamKinase, this test may be just what the doctor ordered. 

The extensive amount of biochemistry, microbiology, and medical coding involved in securing a diagnosis of PANDAS/ PANS can certainly create a smoke screen. Treatment of this condition can produce a similar conundrum! Fortunately, clinical guidelines were recently formulated by a panel of international experts; we will discuss these recommendations in our sequel on therapy.


Kristi Wees is a chemist and patient advocate for children with disabilities. Her web site is: www.empoweredadvocacy.com.