SAN FRANCISCO – Oral corticosteroids appear to be beneficial in treating flares of pediatric acute-onset neuropsychiatric syndrome, or PANS, according to Margo Thienemann, MD.
“Corticosteroids shorten the duration of flares, and if you treat patients early in their first episode, their overall course seems to be better,” said Dr. Thienemann, a child psychiatrist at Stanford (Calif.) Children’s Hospital.
She is part of a multidisciplinary Stanford PANS clinic, together with a pediatric immunologist, a pediatric rheumatologist, two nurse practitioners, a child psychologist, and a social worker, all devoted to the study and treatment of the debilitating condition.
Dr. Thienemann presented the findings of a retrospective, observational study of 98 patients at the PANS clinic who collectively had 403 disease flares. Eighty-five of the flares were treated with 102 courses of oral steroids, either in a 4- to 5-day burst or longer-duration regimens of up to 8 weeks. Dosing was weight based and averaged roughly 60 mg/day. Treatment response was assessed within 14 days after initiating short-burst therapy or at the end of a longer course.
Dr. Margo Thienemann
When a child’s first episode of PANS was treated with oral steroids, the episode lasted for an average of 10.3 weeks; if untreated, the average duration was 16.5 weeks, Dr. Thienemann reported at the annual conference of the Anxiety and Depression Association of America.
Improvement of neuropsychiatric symptoms began on average 3.6 days into a course of oral steroids. That improvement lasted an average of 43.9 days before the next escalation of symptoms.
Longer treatment was better: Each additional day of steroid therapy was associated with a 2.56-day increase in the duration of improvement of neuropsychiatric symptoms in a logistic regression analysis adjusted for age, sex, weeks since onset of current PANS illness, use of cognitive-behavioral therapy during flares, antibiotic therapy, and the number of psychiatric medications a patient was on.
On the other hand, each day of delay in initiating oral corticosteroids was associated with an adjusted 0.18-week longer flare duration.
No improvement in PANS symptoms occurred in patients who developed an infection within 14 days after initiating corticosteroids. Among 31 such patients, 11 had no response to steroids, and only 6 were complete responders. In contrast, among a matched group of 31 patients without infection, there was 1 nonresponder, and there were 12 complete responders.
The Stanford group now is using intravenous corticosteroids as well to treat PANS. Although the group is still collecting data and isn’t yet ready to report results, Dr. Thienemann said intravenous therapy looks very promising.
“We’re seeing a more dramatic response with IV steroids, and with [fewer] side effects,” she said. “With oral steroids, patients become more labile for a day or two, and everything gets worse for that time before things start getting better.”
PANS is a strikingly abrupt-onset disorder. It is defined by dramatic onset of obsessive-compulsive disorder over the course of less than 72 hours and/or severe eating restriction, with at least two coinciding, debilitating neuropsychiatric symptoms. These PANS-defining symptoms may include anxiety, mood dysregulation, irritability or aggression, behavioral regression, cognitive deterioration, sensorimotor abnormalities, and/or somatic symptoms.
The average age of onset of PANS is 7-9 years. The course is typically relapsing/remitting.
“The symptoms are largely psychiatric. We see huge separation anxiety. And aggression – biting, hitting, and kicking in sweet kids who suddenly go crazy,” Dr. Thienemann said in an interview. “They regress behaviorally, have foggy brain, can’t process information, and they have frequent urination and bed-wetting, even if they never did that before. And their handwriting deteriorates.
“We think it’s probably basal ganglia inflammation,” she explained. “The same way a patient might immunologically attack his joints or heart after strep infection, we think it’s brain inflammation resulting from an abnormal immune response to infection.”
This postulated etiology is supported both by PET brain imaging studies and several animal models of PANS, she added.
If the symptoms are associated with a group A streptococcal infection, the disorder is called Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections, or PANDAS, which was first described in 1999 and predates PANS as a defined entity.
Based on the encouraging Stanford experience, a formal double-blind, placebo-controlled, randomized trial of corticosteroid therapy in patients with PANS is warranted, Dr. Thienemann said.
Awareness of PANS as a real entity is “getting better” among general pediatricians, according to the child psychiatrist.
“I think more and more it’s no longer a question about whether this exists,” she said. “Now, it’s a matter of disseminating treatment guidelines.”
The PANDAS Physicians Network has already released diagnostic guidelines. Preliminary treatment guidelines have been developed and will soon be published separately in immunology, infectious diseases, and psychiatry/behavioral medicine journals.
Dr. Thienemann reported having no financial conflicts regarding her study, which was supported by Stanford University.