New Treatment Guidelines Set for PANS/PANDAS

In July, Susan Swedo, M.D., director of the Pediatrics and Developmental Neuroscience Branch of the National Institute of Mental Health (NIMH), along with a national panel of experts, published comprehensive treatment recommendations for Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS), now considered a subset of PANS, in the Journal of Child and Adolescent Psychopharmacology.

PANS/PANDAS are characterized by an unusually abrupt onset of symptoms of obsessive-compulsive disorder (OCD), tics, or restricted eating, and presumed to be triggered by a throat infection or other disease mechanisms.

A work group of experts reviewed the published literature on PANS/PANDAS and drew upon their combined clinical experience with more than 1,000 children with PANS/PANDAS to develop the recommendations. The group decided that treatment of PANS should involve a three-pronged approach that uses psychiatric medications when appropriate to provide symptomatic relief, antibiotics to eliminate the source of neuroinflammation, and anti-inflammatory and immune modulating therapies to treat immune system disturbances.

The treatment guidelines are divided into three clinical focus areas:

• Psychiatric and behavioral interventions to address OCD symptoms, eating restrictions, anxiety, irritability, and more.

• Immunomodulatory therapies, such as oral corticosteroids, that target the neuroinflammation and post-infectious autoimmunity commonly seen in PANS/PANDAS.

• Treatment and prevention of the streptococcal and other infections that underlie these neuropsychiatric conditions.

PANDAS is set in motion by antibodies directed toward the streptococcal bacteria that mistakenly cross-

react with the basal ganglia of the brain. This misdirected immune response produces an abrupt onset of neuropsychiatric symptoms, according to NIMH researchers who first proposed the hypothesis in the early 1990s.

A more recently defined condition (2012), PANS includes a range of triggers and multiple etiologies, not just strep infection, as in PANDAS. Still, in cohorts of well-characterized PANS patients examined by these experts, evidence of post-infectious autoimmunity or neuroinflammation was found in more than 80 percent of the cases, according to the new guideline report.

The unusual and startling behaviors associated with PANDAS and PANS often prompt parents to ask for a referral to a psychiatrist or psychological services, said Margo Thienemann, M.D., clinical professor of psychiatry at Stanford Medical School and co-director of the PANS Program at Stanford Children’s Health. Children may become overly irritable and have mood swings, sleep disturbances, anxiety attacks, urinary problems, attention and concentration difficulties, or regress into “baby talk.”

Thienemann, a co-author of the new guidelines, told Psychiatric News, “These patients should receive a thorough medical evaluation and certainly, a throat culture. We should remind ourselves that mental illnesses are also medical illnesses.”

Along with a complete medical and psychiatric history and physical exam, clinical assessment should include laboratory testing of blood and possibly cerebrospinal fluid, and selected imaging procedures, according to the guidelines. Even in children without symptoms of pharyngitis, a throat culture should be obtained to exclude the possibility of an occult strep infection as the inciting agent, Swedo told Psychiatric News.

“If the culture is positive, a course of antibiotics should be given immediately to clear up the infection and the symptoms will subside. Meanwhile, the clinician may prescribe NSAIDs or prednisone to calm down the immune system. Some children may also need psychotherapy while they’re getting better,” Thienemann advised.

Physicians should note that PANS/PANDAS is a diagnosis of exclusion. “The diagnosis should be made only when symptoms are not better explained by a known neurological or medical disorder, such as Sydenham chorea, autoimmune encephalitis, neuropsychiatric lupus, central nervous system vasculitis, and others,” according to the guidelines.

This research was funded by Auspex Pharmaceuticals, NIMH, Shire Pharmaceuticals, Pfizer Inc., F. Hoffmann-La Roche Ltd., AstraZeneca Pharmaceuticals, Centers for Disease Control and Prevention, Massachusetts General Hospital, Sunovion Pharmaceuticals, Neurocrine Biosciences, Psyadon Pharmaceuticals, the PANDAS Network, the International OCD Foundation, and the Tourette Syndrome Association. ■