PANS/PANDAS and NIH Women's Health Research

Signs, Symptoms, and Risk Factors

Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are rare conditions that typically appear during childhood, between age 3 and puberty. These conditions are thought to impact the basal ganglia in the brain and are characterized by the sudden, dramatic appearance of obsessive-compulsive disorder symptoms and other severe neuropsychiatric symptoms, such as anxiety, depression, irritability, motor or vocal tics, and sleep disturbances.^{1 - 3} PANS is a broad syndrome that may be triggered by infections, immune disruptions, genetic predisposition, or environmental factors, whereas PANDAS is a specific syndrome that is linked to streptococcal (strep) infections such as strep throat or scarlet fever. Historically, PANS emerged from the observation that some individuals who met the diagnostic criteria for PANDAS did not have evidence of a strep infection. Both conditions involve rapid, severe symptom onset that may fluctuate over time.^{2 - 4}

The causes of PANS are unknown, but research suggests that immune system activation, possibly due to infection or environmental triggers, leads to sudden neuropsychiatric symptoms.^{2 , 4} In PANDAS, the primary hypothesis has historically been that an autoimmune process triggered by a strep infection targets healthy brain tissue, causing neuroinflammation, although evidence of frank neuroinflammation is limited. In addition, the specific antibodies that are involved in this process have yet to be identified.² By definition, though, a temporal association with a strep infection is a key criterion for diagnosing PANDAS,⁵ whereas PANS may follow a range of infectious or immunological triggers.

Impact on Women's Health

PANS and PANDAS are considered childhood-onset conditions, although it is possible--but unlikely--for an adult to develop these conditions.² PANS and PANDAS fall within the broader category of autoimmune disorders, which generally have a higher prevalence in females than in males. This is possibly due to underlying genetic influences, including factors linked to sex hormones and the X chromosome.^{6 , 7} However, several studies have reported that PANS and PANDAS are more commonly diagnosed in boys than in girls, although these differences have not always been statistically significant.^{7 - 11} Evidence also suggests that disease chronicity and symptom expression may vary by sex.⁷ A survey of 698 patients with PANS found that females, especially postpubertal females, were more likely than males to experience chronic psychiatric symptoms, including general anxiety, irritability, excessive worry, moodiness, and sadness.⁸ Another study found that females with PANS were less likely to exhibit aggressive behavior than males.⁹

Diagnosis and Treatment

No definitive laboratory tests exist to diagnose PANS or PANDAS. Instead, clinicians rely on diagnostic criteria, including sudden onset of obsessive-compulsive disorder or restrictive eating. This must be accompanied by at least two other neuropsychiatric symptoms, including anxiety, depression, or other dramatic behavioral shifts; lack of an alternative explanation for symptom onset; and, in the case of PANDAS, a history of a recent strep infection.^{2 , 3}

Treatment is multidisciplinary and depends on the severity of symptoms and presentation. Clinicians often use cognitive behavioral therapy, selective serotonin reuptake inhibitors, and antibiotics for strep infections.^{2 , 3 , 12 - 15} Nonsteroidal anti-inflammatory drugs, oral corticosteroids, and intravenous administration of immunoglobulins are sometimes used, but the evidence for their effectiveness is inconclusive.^{2 , 3 , 14} Moreover, immunoglobulin treatment carries the risk of adverse effects. Some children with PANS or PANDAS recover fully, especially if treatment is promptly started, while others may experience recurring episodes or persistent symptoms.²

Ongoing Research

Given the heterogeneous nature of PANS and PANDAS, researchers are working to define the true prevalence of these conditions and identify objective biomarkers. Current research efforts are also focused on developing clear, standardized terminology for PANS disease presentation and progression;¹⁶ exploring the role of inflammation in disease onset and progression;¹ and evaluating the effectiveness of specialized treatments, which requires well-designed, randomized, placebo-controlled clinical trials.^{3 , 17}

The NIH Translational Immunopsychiatry Unit (TIU) is an integrated clinical, basic, and translational research program that studies immune processes that contribute to neuropsychiatric illness. Recently, the TIU built and validated a platform that allows scientists to map human antibody repertoire to identify autoantibodies, histories of infections, and associations between the two. Although the TIU is not currently conducting clinical trials in people with PANS or PANDAS, it is using this platform and other technologies as part of an NIH-funded intramural research project to map the antibody repertoire in biospecimens from people with neuropsychiatric illnesses, including PANS/PANDAS.¹⁸

The NIH Autoimmune Brain Disorders Program is also involved in research on PANS/PANDAS and offers evaluations for individuals with these conditions who have evidence of neuroinflammation or immune dysregulation.