Researchers seek to better understand PANS/PANDAS

Pediatric acute neuropsychiatric syndrome (PANS), along with the related pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), may be a controversial diagnosis, but a new study seeks to better characterize the diagnosis.

The analysis of nearly 200 children with PANS found that a substantial proportion had “subtle, systemic inflammation,” raising “the possibility that the psychiatric symptoms reflect a brain response to a global process,” said Jennifer Frankovich, MD, of Stanford University in Palo Alto, California, and colleagues, writing in JAMA Network Opened.

They noted an increased risk of arthritis in their cohort and concluded that PANS “may be part of a multisystem inflammatory disorder rather than an isolated psychiatric or neuroinflammatory disorder.”

The term PANDAS was coined in 1998 by a team at the National Institute of Mental Health, which described 50 children who suddenly developed features of obsessive-compulsive disorder (OCD) or tics after exposure to group A streptococcus, according to Dr. J. Patrick Whelan of the University of California Los Angeles, who wrote an accompanying commentary.

PANS is broader, with the rapid onset of OCD symptoms after any type of infection, not just strep. Those symptoms are often accompanied by sleep disturbance, changes in urine, cognitive and behavioral problems, and emotional imbalance.

Yet few doctors are trained to recognize the condition, says Aravindhan Veerapandiyan, a pediatric neurologist at Arkansas Children’s Hospital in Little Rock and co-director of the Childhood Post-infectious Autoimmune Encephalopathy Center of Excellence.

“It’s still a controversial diagnosis, and there are still many healthcare providers who don’t believe (PANS and PANDAS) exist,” Veerapandiyan said MedPage TodaySome reasons for that skepticism include “a lot of not-so-evidence-based practices” and a lack of established biomarkers to confirm the diagnosis, he said.

Yet researchers know more about the condition than they did two decades ago. The prevailing theory is that an infection triggers certain antibodies that cross the blood-brain barrier and cause inflammation in the brain, particularly the basal ganglia.

The study by Frankovich and colleagues evaluated 193 patients with PANS who were treated at their clinic from September 2012 to December 2021. The average age was 7.5 years, and children were followed for an average of 4 years. More than half were boys (58%), and 83% were white.

They found that 54% had nonspecific markers of autoimmunity, while only 12% had markers of immune dysregulation or inflammation. Also, 36% had signs of vasculopathy.

More than a quarter (28.3%) developed arthritis before the age of 14. Of these, about two-thirds met criteria for enthesitis-related arthritis, which affects the joints of the lower limbs, and almost half met criteria for spondyloarthritis, characterized by inflammation in the spine. In addition, 7.5% developed another autoimmune disease.

Whelan wrote in his commentary that the children who developed arthritis had an “unusual rheumatic disease profile,” with 56 percent having Achilles tendon enthesitis, 64 percent having inflammatory back pain, and 69 percent having sacroiliac joint tenderness. Only 2 percent of the group “developed the more typical forms of childhood arthritis, namely systemic lupus or juvenile idiopathic arthritis,” he wrote.

“It confirms an observation that I’ve made in our practice, which is that there is a relatively large number of children in this population who develop a very specific form of arthritis,” Whelan said. MedPage Today.

He said he’s had success treating children with PANS/PANDAS using this model: “This is something neurologists would never think of, is giving kids like this a drug for arthritis. But suddenly they’re back in school, they’re productive citizens, and eventually — many of them — they outgrow the behavioral problems.”

Veerapandiyan isn’t so sure. While he agreed that PANS is an autoimmune inflammatory disorder, he said, “I haven’t seen anyone develop rheumatoid arthritis or other types of inflammatory conditions that manifest clinically.”

He noted that the lead author and director of the clinic where the patient population came from is a rheumatologist. “So the patients who come to the clinic most likely have rheumatologic problems.”

The authors have not provided an answer MedPage Today request for comment.

Veerapandiyan also cautioned that without a control group, it’s difficult to know how the inflammation profiles compare to those of people without PANS/PANDAS. “This is good information,” he said, but added that he doesn’t plan to test his current case for the lab markers evaluated in the study.

Whelan said he sees kids whose symptoms may have developed after other infections like COVID, which in the past may not have fit neatly into psychiatric or neurological treatment. “So like a lot of other things, like pulmonary COVID for example,” he said, “it’s kind of the rheumatologist, because we really are the consultants of last resort.”

Parents and patients with PANS/PANDAS often describe frustrating medical encounters marked by skepticism, unfamiliarity, and difficulty diagnosing what appears to be OCD or bipolar disorder. Some major children’s hospitals even state that they will not treat patients with PANS/PANDAS. Whelan described families shocked by their child’s sudden changes in behavior and caregivers forced to put their careers on hold to care for a child who was unable to attend school.

Veerapandiyan, who normally uses antibiotics, anti-inflammatories and steroids to treat the condition, said immunosuppressants have also shown promise, anecdotally. He is also leading a clinical trial of intravenous immunoglobulin for the condition.

More research is needed on PANS/PANDAS, he said, and “more efforts should be made to really create awareness and education about more appropriate information for families and health care providers about this.”