How did you first learn of PANS/PANDAS and what motivated you to begin treating children with these disorders?
I began as an internist with an interest in rheumatology, but ended up going into psychiatry, and then child psychiatry. I ran the OCD clinic at Stanford and had heard about PANS and PANDAS from a fellow who had worked at the NIH. Then I noticed that some of my patients with OCD would improve with antibiotics.
Do you ever treat children who did not have an abrupt or acute onset, and if so, do they respond similarly to children who did have an abrupt onset?
Because of our research orientation, our clinic now sees only children who meet very strict clinical criteria. I have seen children who have had episodes of infections with one or two PANS symptoms in the past that did not meet criteria, in which the course of symptom development or severity was not noted, perhaps because symptoms were milder, who then later developed a separate full PANS flare. People who have had repeated episodes appear to be more difficult to treat than those who receive care with the first episode.
Are you aware of any children with an autism diagnosis who actually had PANS?
People can have both autism and PANS as separate diagnoses. As well, if people with autism are having trouble with anxiety, OCD, mood, etc. from PANS, treating the PANS may help them be more available for social interactions because their anxiety and mood troubles interfere less.
What about bipolar disorder, oppositional defiant disorder, mood disorder-NOS, Tourette's, etc?
Symptoms of each of these disorders can be seen in PANS. The definition of PANS is a Research Diagnostic Criteria, written to help make researchers more likely to be looking at the same disease process in their research. Research into inflammatory and post-infectious issues in mood disorders, schizophrenia, OCD and tic disorders suggest that they may be contributory to the risk of developing these neuropsychiatric problems.
How old was the youngest patient you've diagnosed with PANS? Can this persist into adulthood?
We have seen three and four year olds with PANS. We don’t have long-term data, but clinical experience suggests that residual OCD, tics, ADHD, and other symptoms can persist.
What percentage of your patient population requires IVIG and how often is more than one round of IVIG necessary?
We decide on a case-by-case fashion about IVIG. Often it takes several appeals to insurance companies to get authorization and many months can pass. So we hardly use it as a first-line treatment. Research has not yet been done to determine how many rounds are right or how to time them.
What percentage of your patient population has required Rituximab?
Probably 1-2%. It is not something we use first or often.
Do you see a difference in outcomes when children are treated promptly versus when they have been sick for years?
Prompt identification and treatment generally yields much better results.
In your opinion, why hasn’t PANS/PANDAS moved beyond controversy?
People are worried that children might not get evidence-based treatment for OCD. They may be concerned that children could be erroneously diagnosed and treated for PANS. There is also the worry about over-use of antibiotics and evolution of antibiotic-resistant microorganisms. Proving the mechanism is difficult; the brain is an organ that is hard to biopsy and you would not purposefully infect a child to see if they get PANDAS!
We don't know how common PANS is. Strep and other infections are common in children. Most people with strep do not get PANDAS. Perhaps only a certain strain of strep causes it. Only susceptible children get PANS/PANDAS. Many children with PANS have a family history of auto-immune or auto-inflammatory disorders.
No “biomarker” (blood test, imaging finding, EEG profile, etc) has been found that is consistently and specifically linked to PANS. Progress is being made in NMDA-R encephalitis because a biomarker has been found.
Is there any research in the pipeline that you’re excited about or that you think will make a significant difference in the lives of children with PANS?
At Stanford we have a bio-repository and we are analyzing data from our database. Specifically we are looking at HLA phenotypes, monocytes, group A strep toxin that is causing T17 skew, vasculitis markers, and also treatment responses to NSAIDs, IVIG, Rituximab, and Methotrexate. We are also looking at the prevalence of hallucinations in this population as well as pain, fatigue, and exercise intolerance. We are looking at cognitive changes.
Outside of Stanford, some PET studies have shown evidence of activation of inflammatory brain cells in children with PANDAS that change with treatment. Mouse studies are finding that inflammatory cells migrate to mouse brains from their tonsils/adenoids after they have had multiple strep infections. Those cells cause the release of specific, identified inflammatory cytokines. Some large Danish registry studies show that repeated infections, especially in those with family history of autoimmune disorders remarkably increases the risk of OCD and mood disorders
~A special thank you to Dr. Margo Thienemann for allowing Anna Conkey, President of The Foundation For Children With Neuroimmune Disorders to interview her.