Diana Pohlman says her son, who was 7 years old at the time, had been easygoing up to that point. But he developed severe obsessive compulsive disorder (OCD) symptoms overnight. He became paranoid -- worrying about things like radiation from the TV and light switches. He had tics and anorexia and started having frequent episodes of rage.
“He was not anyone I recognized. He was a completely different child,” she says. “It was a nightmare. At first I thought maybe he had been molested. Then I thought he had a brain tumor.
“He became so delusional he would climb on the roof thinking it was the front door. He would jump in front of cars and out of moving cars, and he had self-harm fantasies. He was afraid to leave the house. We had to pick him up and wrap him in a sheet to get him out of the house. At the age of 7,” Pohlman says.
The search for answers was long and expensive. After many months, the family found their way to a psychiatrist who knew about a disorder called pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, or PANDAS, a condition she says several specialists didn't know about. That led to medical treatment that included long-term antibiotics, having his tonsils and adenoids removed, and eventually two rounds of immunoglobulin, or IVIG treatments.
Recovery was slow, but after 2 years, by the age of 9, Pohlman says the severe symptoms stopped. For another 2 years, he had what she calls mild and manageable symptoms that eventually dissipated.
But rather than move on from PANDAS, the boy’s mother decided she needed to help other parents trying to figure out these mysterious symptoms. She founded the nonprofit PANDAS Network in 2009 to raise awareness, support families, and push for more research to better understand how to diagnose and treat the condition.
“When I realized doctors didn’t understand it, I thought I better not quit working on this because how will anyone else ever get help,” Pohlman explains. “It is abysmal. It has been shocking how misinformed doctors are about the term 'PANDAS.' ”
Little is known about how or why the syndrome happens, and not all doctors believe there is a connection. The American Academy of Pediatrics does not recognize a link between strep and the syndrome.
“You will not find consensus from pediatric infectious disease doctors that PANDAS even exists, much less what to do about it and how to manage the patients,” says Meg Fisher, MD, a pediatrician and infectious disease specialist at Unterberg Children's Hospital at Monmouth Medical Center in Long Branch, NJ. “We still haven’t had the definitive article or study or demonstration to really get some solid clinical evidence behind this. My problem is, even if you believe in the syndrome, it’s totally unclear what you should do to help those patients. All of the information is anecdotal.”
What Is PANDAS/PANS?
Susan E. Swedo, MD, at the National Institute of Mental Health (NIMH), first identified PANDAS in the 1990s after she reported on a link between the fast onset of OCD and group A streptococcus, more commonly known as strep.
PANDAS happens when strep triggers a misdirected immune response that causes inflammation in a child’s brain. Pediatric acute-onset neuropsychiatric syndrome, or PANS, is a larger umbrella term that has to do with cases with a trigger other than strep, including infections like walking pneumonia or the flu.
Both disorders appear in childhood, typically between the ages of 3 and 12. While blood tests may help identify infections, there are no lab tests or other indicators for PANDAS or PANS.
Doctors diagnose the syndrome when children suddenly get severe OCD or eat a lot less food, along with at least two of the following symptoms: anxiety, depression, irritability or aggression, behavioral regression, ADD- or ADHD-like symptoms affecting schoolwork, sensory or motor problems, troubled sleep, and frequent urination.
The PANDAS Network says in some cases, the emotional symptoms can weaken children and make them homebound. Other children are OK at school but fall apart at home. The NIMH describes the start of symptoms as “dramatic,” happening “overnight and out of the blue.”
“The consensus of scientists and clinicians is that it needs to be sudden and severe,” says Margo Thienemann, MD, co-director of the PANS program at Stanford University Medical Center in California. “Sudden can be overnight. Some people can say exactly what time it started or that it happened over a couple of days. But they all say this isn’t their child anymore. Even if they don’t believe someone can be possessed, it feels that way. What happened? Why are they doing these things? Why can’t they stop?”
Swedo estimates that it impacts about 1% of elementary school-aged children and is likely under-diagnosed. The PANDAS Network estimates 1 in 200 children have it. Thienemann says her program at Stanford has seen more than 250 patients since it started in 2012. But she says that since their staff is small, they have to narrow down who gets in. One year, they turned away 1,000 patients because they couldn’t handle any more.
Thienemann says this is why they have helped write guidelines to allow health care providers to identify and treat these children. “It takes a multidisciplinary team to manage. A psychiatrist, pediatrician, or rheumatologist can’t do it alone. You need all these different vantage points to diagnose and coordinate care,” she says.
There are now PANS centers in California and Arizona, and some doctors around the country treat the disorder.
This year, an expert panel that published treatment guidelines says the best first treatment for severe episodes is to treat the infection, if it is still present, with antibiotics. Then inflammation needs to be addressed, with medications like non-steroidal anti-inflammatories, corticosteroids, and intravenous immunoglobulin (IVIG).
The NIMH says research suggests IVIG can ease symptoms and may be used in severe PANDAS cases, but it warns it has many side effects -- including nausea, vomiting, headaches, and dizziness -- and there is a chance of infection with this sort of procedure. Parents say it is also expensive and often not covered by insurance.
Some families say they also see improvement when they have their children’s tonsils and adenoids removed, although no studies show that works.
Not all in the medical community agree that strep or other infections can trigger these kinds of behaviors. There is also much debate about whether treatments are effective.
While the American Academy of Pediatrics does not recognize a link between strep and PANDAS, a March 2017 article in AAP News, sent to the group’s 66,000 pediatrician members, discusses the disorders and the controversy around them. While it’s not the group’s official policy, the article says pediatricians should consider PANS anytime a child “has an abrupt behavior change with obsessive thoughts,” and it points them to material that shows them how to diagnose it.
Fisher says it's complicated for pediatricians, since there is no evidence that taking out tonsils and adenoids is helpful or that antibiotics work. She says many pediatricians worry that young patients will become resistant to antibiotics if you prescribe them long-term, and many have concerns about IVIG side effects.
“I understand the parents’ frustration, because finding a physician for these patients is very difficult. There are a lot of doctors who are, quote unquote, PANDAS specialists, but there is nothing that is evidence-based about what they are doing,” she says. “Our goal is first do no harm, and it is hard to know how best to help these patients. It is a very frustrating thing. I wish someone would come up with some solutions.”
Thienemann says most parents who find their way to her program are frantic because they can’t get help anywhere else. “Part of that desperation is nobody would listen to them. People say my pediatrician won’t do anything, and my child is trying to jump out of moving cars or a window. They can’t get out of the house, can’t sleep, are urinating on themselves, and have severe separation anxiety,” she says.
Parents say it is obvious something isn’t right.
“I thought she had schizophrenia or severe mental illness,” says Kelly, a mother in Maryland who asked that we not use her last name to protect the privacy of her 7-year-old daughter, Maggie, who has PANDAS. “It was rapid-onset OCD, and then we were spending our entire life trying to keep her from jumping out of cars, hurting herself, biting us, and losing her mind.”
“There is something medically wrong. There isn’t a finger to be pointed. There are questions to be asked and answered,” adds Ali Claypoole, whose son, now 9 years old, first showed PANDAS symptoms at the age of 6. “Our world is turned upside down, and from where I am, it’s almost like parents are more informed than the doctors. I find the civilian community is much more understanding, interested, and willing to learn about this than the medical community. It makes me mad.”
More research is now being done.
In a 2017 large-scale study of key parts of the PANDAS theory, researchers looked at 17 years of data out of Denmark and found that young patients with a positive strep test had higher chances of having of mental disorders, especially OCD and tic disorders, compared with those without a positive strep test. Non-strep throat infections also carried a higher chance of these types of mental disorders in children, although it was less -- perhaps pointing to the chance that other infections can trigger the symptoms.
In 2016, Dritan Agalliu, PhD, an assistant professor in the Department of Neurology at Columbia University Medical Center in New York City, published a study showing that immune cells produced in the nose after multiple strep infections appear to be the culprit for the disease. These cells enter the brain via the nerves that are responsible for the sense of smell, and they damage the blood vessels and synapses in the brain.
Agalliu says this research helped explain a crucial step in the disease: how antibodies that the body makes to attack strep or other infections cross the blood/brain barrier in these children and attack parts of their brain by mistake; similar to what happens in other autoimmune diseases of the brain, like multiple sclerosis.
The NIHM recently awarded Agalliu nearly $2 million to keep studying the disorder. He says it should be called post-streptococcal basal ganglia encephalitis, or inflammation of the brain. He’s also doing research funded by a private donor, looking at genetic chances of having the disorders to understand why a small number of children who get multiple strep infections are prone to get the disease.
“It is really the brain inflammation that is central to this disease. If we think about PANDAS/PANS this way, it will relieve a lot of controversy and make therapies more acceptable for patients,” Agalliu says. “I am hoping with our next publication, we can alleviate any potential question that this is an autoimmune disease.”
There’s also increasing interest in looking at PANDAS as a type of Sydenham chorea, defined by abnormal movements, OCD, mood swings, and other emotional symptoms that follow strep infection.
The NIMH now has a group for PANDAS and PANS. The PANDAS Network is working to make information about the disorders part of continuing medical education for pediatricians, and a working group has created handouts to educate school personnel nationwide to help children with these disorders get back to their classrooms.
So will children outgrow PANDAS? Like most other things associated with this disorder, there is no consensus.
Doctors who focus on the disorders say when patients can get to them, improvement is possible. “If we get people as early as possible, maybe even at the onset of illness, I think we do a good job of being able to tamp down inflammation and help them a lot and maybe get them all the way better,” Thienemann says. “If someone has been dealing with it for 10 years, I think they may develop ongoing autoimmune problems and there may be damage to their brain. Recovery might not be as complete, but I think we can still help them.”
Three years after he first showed symptoms, Claypoole’s son had a full remission at the age of 9 after IVIG treatments. But after a few months, he got strep again and the PANDAS symptoms returned, but they were less severe. Kelly’s daughter Maggie has seen her symptoms subside for a while, only to return. Her doctors prescribe antibiotics and anti-inflammatories after each new episode. She takes both medications daily for months on end. She has also had two rounds of IVIG. “Every time we do an intervention, the baseline gets better, but it doesn’t end the problem. She is not symptom-free,” Kelly says.
Pohlman says her son, now 17, is a straight-A student who plays football and the cello and is applying to college. He is symptom-free.
“Once I understood that Garrett's brain was on fire from an infectious illness, I barely could believe his body would have the capacity for a full recovery,” she says. “Could he have the normal life I had expected for my child? So I look at him now in amazement.”