PANDAS emerged in the late 1980s in the wake of a resurgence of rheumatic fever in Pennsylvania, Utah and Missouri. Rheumatic fever is an immune response to group A streptococcus, the bacterial strain that causes strep throat and scarlet fever. It arises when those infections are not treated properly, usually in children. In the worst cases, it can lead to heart failure or permanent heart damage. Some people need to take antibiotics for a decade or more.

Up to 30 percent of children with rheumatic fever develop distinctive motor and behavioral traits called Sydenham chorea or, less commonly these days, Saint Vitus dance, after the patron saint of neurological conditions. Children with this condition exhibit jerky, involuntary movements of their hands, feet and face. By some accounts, they also become irritable and prone to emotional outbursts, have trouble concentrating and temporarily lose their ability to read and write. A frequent complaint heard from the mother is that the character of her child is completely changed, wrote Canadian physician William Osler, who first characterized Sydenham chorea in 1894.

During the rheumatic fever outbreak, Swedo sent questionnaires to 37 parents, asking them about their childrens behaviors. She says she hoped to find a brain-based explanation for OCD, which had, until then, largely been credited to harsh parenting techniques. The findings confirmed her suspicions: Children with Sydenham chorea had significantly more obsessive thoughts or behaviors than children with rheumatic fever alone. Based on follow-up interviews, Swedo determined that three children diagnosed with Sydenham chorea met the diagnostic criteria for OCD.

Swedo then inverted her approach. Rather than seeking out children with rheumatic fever, she began studying children with OCD and Tourette syndrome, and swabbing their throats for evidence of a strep infection. She often found it which is not surprising because it is a common infection, and many children also carry the bacteria without getting sick. What was surprising, Swedo says, was what happened when she started treating those children.

She recalls one child who refused to swallow his spit, preferring, instead, to stockpile it. He had three cups under his bed, she says. When she treated him with penicillin, she says, he responded beautifully; his obsessive-compulsive symptoms disappeared. He then had another strep infection, and the OCD-like behavior came roaring back. In another child, she tried plasmapheresis, a technique to separate the childs blood cells from the plasma and strip out the germ-fighting antibodies circulating in his system. She says that led to an 80 percent decrease in the boys OCD traits, according to his parents.

Based on those observations and more over the next decade, Swedo came to believe that an immune response to infection can trigger an improperly diagnosed class of psychiatric conditions. She would go on to investigate and rule out other connections between infection and conditions of brain development, including the spurious association between Lyme infection and autism. In 2006, she proposed a trial to test chelation therapy, which some parents of autistic children pursue based on the bogus belief that mercury and other heavy metals in vaccines cause the condition. Critics called the trial unethical and a waste of funding, and it was ultimately abandoned due to safety concerns.

Theres going to be diagnostic confusion whether a child has a late presentation of autism or if they have PANDAS. Susan Swedo

It was PANDAS that would become Swedos legacy. In 1998, Swedo proposed five criteria to diagnose PANDAS: the presence of OCD or a tic disorder, sudden onset prior to puberty, a waxing and waning pattern of trait severity, an association between strep infections and behavioral traits, and neurological abnormalities such as jerking movements or problems with coordination. Despite the clear, testable criteria she laid out, the definition of PANDAS proved elastic in the hands of practitioners. By 2008, one study had found that only 39 percent of children diagnosed with PANDAS actually fit Swedos original definition. So many children were diagnosed, in fact, that Stanford Universitys multidisciplinary PANDAS clinic the first of its kind when it opened in 2012 sees children from within only a seven-county area and only if they agree to participate in research.

Given the surge of interest, the NIH launched a $3 million multicenter study the largest and most rigorous analysis of the condition. The researchers followed 71 children who met PANDAS diagnostic criteria over two years and compared them with children who had traits of Tourette syndrome or OCD but not PANDAS. Two landmark studies, published in 2008 and 2011, found that in 91 percent of all PANDAS cases, there was no association between the timing of strep infections or presence of strep antibodies and flare-ups of OCD or tics. Even though children with PANDAS were more likely to receive antibiotics than the other children were, the researchers could detect no difference in the number of flare-ups the children experienced.

The NIH makes no mention of these studies on its information pages about PANDAS, which Swedo helped draft. To be fair, the results left just enough room for doubts to creep in. Many strep infections go unnoticed and can trigger immune reactions that standard tests do not detect. The researchers consulted Swedo before the trial, but she says they approached it with an agenda to disprove PANDAS. For example, she says, most of the PANDAS children in the study had Tourette syndrome over a long period of time and showed no signs of abrupt-onset OCD, PANDAS hallmark behavioral trait. However, Kaplan, an investigator on those trials, says all of the participants fit Swedos published definition.

Swedo and her colleagues later proposed a new, broader condition that would better fit the state of the evidence: pediatric acute-onset neuropsychiatric syndrome, or PANS. This umbrella diagnosis is not restricted to children with strep or any other type of infection. It might even be caused, for instance, by environmental factors or metabolic disorders. Nor is it limited to young children: PANS can strike anyone up to the age of 18. The main requirement for PANS is the acute onset of OCD or restricted food intake, though the working guidelines make it clear that mild, non-impairing obsessions or compulsions do not rule out the syndrome.

One 2015 study in mice revealed how strep infections could cause brain inflammation, but no studies have followed a large group of children to try to link infections and PANDAS since the NIH-funded studies. Asked why no one has attempted a new study, Swedo says the field has moved on, adding, You cant fight a felonious report with additional data.

Link:
How a controversial condition called PANDAS is gaining ground on autism - Spectrum