REVIEW OF: Melamed I et al, J Child Adolesc Psychopharmacol 2021;31(2):118–128.

Pediatric acute-onset neuropsychiatric syndrome (PANS) is defined by dramatic, abrupt onset of obsessions, compulsions, and/or eating restrictions along with two neuropsychiatric symptoms, most commonly tics, anxiety disorders, urinary difficulties, and oppositional behavior. Because PANS is thought to be an autoimmune disease, researchers have used IV immunoglobulin therapy (IVIG) as a treatment. This study tested an extended IVIG dosing strategy.

Twenty-one patients, 4–16 years old and diagnosed with moderate to severe PANS symptoms on the Pediatric Acute Neuropsychiatric Symptom Scale, were recruited from seven sites. Participants could remain on concurrent prophylactic antibiotics if doses were stable for the prior three months. Most of the patients were male (62%) with mean PANS symptom duration of 4.3 years. Participants received a total of six infusions of 1 g/kg (Octagam 5%) given every three weeks over 18 weeks.

Primary outcome measures included the Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Clinical Global Impressions Scale (CGI-S), and Yale Global Tic Severity Scale (YGTSS) measured at baseline and at one week and eight weeks after the last infusion. The Parent-Rated PANS Questionnaire (PRPQ), developed specifically for this study, captured interim efficacy data at each infusion visit. A subset of patients participated in a 46-week follow-up visit. Patient diaries tracked adverse events.

The IVIG infusions were effective. All primary outcome measures decreased significantly. Scores on CY-BOCS fell by 61.45% (p < 0.0002), CGI-S by 44% (p < 0.0001), and YGTSS by 66.61% (p = 0.0005). Scores on PRPQ did not improve until the third infusion but dropped 52.82% (p = 0.004) from baseline to last infusion. At 46-week follow-up, most improvements persisted except for tics; however, tic severity remained below baseline measures. The treatment was well tolerated; side effects were transient and mild and included post-infusion headache, nausea, and vomiting.

CCPR’S Take:
While the results are promising, this was a small, uncontrolled, open-label trial, and the lack of a control group precludes measuring an effect size. Still, sequential infusion of IVIG seems safe and might be effective in patients with moderate to severe PANS who do not respond to standard therapies.