In the late 1990s, researchers first identified Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, otherwise known as PANDAS. This rare childhood illness is thought to be triggered by strep bacteria, which causes an immune system reaction targeting the basal ganglia and creating antibodies that attack the child’s tissues.
A PANDAs diagnosis may be delivered when a child manifests symptoms related to obsessive-compulsive disorder (OCD) or tics; the symptoms usually appear suddenly and without warning.
Additionally, some children with PANDAS may have anxiety, panic attacks, frequent mood changes, emotional and developmental regression, subtle motor symptoms, frequent need to urinate, visual or auditory hallucinations, refusal to eat, depression and/or suicidal thoughts.
But the underlying reasons for developing OCD related to PANDAS have not conclusively been determined.
Identifying a Possible Explanation
A team of researchers at Yale University has been studying the biological underpinnings of PANDAS and has identified a possible explanation. Their findings are based on clinical research by Kyle Williams, M.D, Ph.D, director, pediatric neuropsychiatry and immunology program at MassGeneral Hospital for Children. His research has looked at serum antibodies and how they affect the brain.
Children with PANDAS have been found to have an elevated level of antibodies that attack cholinergic interneurons (CINs). These neurons connect different parts of the brain and are vital in coordinating activities and regulating basal ganglia function.
These “cross-reactive antibodies” can attack the brain, affecting voluntary motor control, inducing tics and OCD and a variety of neuropsychiatric symptoms, according to studies from the National Institute of Mental Health (NIMH).
Christopher Pittenger, M.D, Ph.D, FAPA, FANA, director of the Yale OCD Research Clinic, noted that the current Yale study is a follow up to an earlier one. The results of the first study mirrored the findings from studies conducted by the NIMH, which found increased binding to CINs in the immunoglobulin G (IgG) antibodies of children with PANDAS.
At Yale, Pittenger is also the co-director of the Neuroscience Research Training Program as well as an associate professor of psychiatry.
In the current Yale study, Pettinger and the other researchers sought to confirm that the cross reaction causes OCD symptoms in a larger cohort.
Pettinger pointed out that the subjects in the study group came from a treatment program developed by Susan Swedo, M.D, who has been studying PANDAS since the 1990s. He pointed out that the control group also came from the same clinic and manifested no psychopathology.
The follow up study included 27 children who met the criteria for a PANDAS diagnosis; the control group consisted of 23 subjects. Fifteen subjects in the study group had not received IVIG, a complicated process in which subjects receive intravenous infusion of immunoglobulin into a muscle, a vein or under the skin.
Pettinger noted that IVIG purifies the antibodies and a select number of children will respond, although some do not.
He pointed out that approximately 95 percent of children get strep at some time or another, but only a small fraction gets PANDAS. “Unfortunately, we don’t know how to determine who is at risk,” he said.
A PANDAS diagnosis still causes some controversy among medical professionals. “Some specialists think every kid gets it and some say none get it, that it doesn’t exist,” he said. “Clearly, it’s real but rare. We do know that two to three percent of children get OCD. We don’t know what fraction of those with OCD will have PANDAS.”
Furthermore, researchers assume that a combination of genetics and the type of strep the child has as well as other environmental factors will have some bearing on the likelihood of developing OCD.
OCD Tied Loosely to Tourette’s Syndrome
CD has also been loosely tied to Tourette’s syndrome. Pettinger reported that 75 percent of children who have Tourette’s syndrome get better by the time they are teenagers.
More boys than girls get Tourette’s and 40 percent of those will develop PANDAS. Tics, often associated with Tourette’s, are quite common in chronic OCD, he pointed out.
Pettinger is currently working on a grant that will enable him and his colleagues to conduct additional studies with different cohorts. “We want to branch out and look at binding patterns,” he said.
Pettinger reported that a PANDAS diagnosis currently relies on clinical observation; if a standard diagnostic test were developed more children would receive a proper diagnosis and effective treatment in a timely manner, he noted.