IMAGINE THAT ONE NIGHT you put your bright, athletic, well-adjusted 8-year-old son to bed, a kid who loves playing baseball and cracking jokes and scarfing down chocolate chip cookies. The next morning, he wakes up as someone entirely different, and in subsequent days turns into someone unrecognizable.
He’s manic, spending hours doing sit-ups or running laps on the driveway — unwilling to sit down even for a minute. He alternates between tears of soul-crushing sadness and tantrums of rage directed at you and your spouse. He’s obsessed with the unhealthiness of food, refusing to eat or drink much of anything. More than anything, though, all the comforting touchstones of his life — home, school, even sleep — have suddenly been transformed into dangers. He seems trapped in a horror movie, his fear unmistakable in the way his pupils have overtaken the irises of both his eyes.
As this bizarre behavior continues, you find yourself staring at your formerly normal, healthy son and you can’t help but wonder, Where did my boy go? You ask yourself: Is this what children of Alzheimer’s patients mean when they talk about looking at a loved one who’s no longer there?
You take your son to your pediatrician, a sympathetic and smart woman who is nonetheless flummoxed. Because some of your son’s symptoms appear to be compulsions, she refers you to a psychologist. Actually, because the need for pediatric mental health treatment dwarfs the supply of mental health professionals, your pediatrician turns to a state referral service called MCPAP, or Massachusetts Child Psychiatry Access Project.
By phone, the consulting psychiatrist instructs your pediatrician to treat your son for obsessive-compulsive disorder, prescribing a Prozac-like antidepressant and recommending that you find a therapist who can guide him through cognitive behavioral therapy to help him “unlearn’’ his new behaviors.
The diagnosis doesn’t sound right to you. Compulsive behavior seems to describe just one strain of his symptoms. And the fact that he literally changed overnight doesn’t compute with what you’ve read about the typical OCD patient, whose behavior changes gradually. Then again, you’re not the expert, and you desperately want your son — your family life — back. So you defer to the professionals.
One day, you find yourself rushing your son to the emergency room. After weeks of unsuccessfully battling with him to eat and drink, he is dehydrated and dangerously underweight. The attending physician comes to talk with you. Peering over his shoulder, you are startled to see the words on your son’s chart: anorexia nervosa. The doctor recommends a book on adolescent anorexia.
“Adolescent?’’ you ask incredulously. “But my son just celebrated his ninth birthday.’’
Yes, the doctor agrees. But you won’t find any books on anorexia for elementary school kids.
When little about your son’s condition improves over the next couple of months, the doctors continue to bump up the dosage of the antidepressant. Because you’ve read enough to know that there are serious questions about the long-term effects of these drugs on the rapidly developing brain of a child, this course of treatment deeply troubles you, especially because it isn’t working. And the cognitive behavioral therapy seems to be equally ineffectual.
As you wait for your son outside the therapist’s office during one appointment, you flip through a copy of Parents magazine and stumble across an article about an obscure condition called Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections, or PANDAS. It feels as though it were written about your son. There’s a chart listing seven symptoms of PANDAS, and in your head you can check off every one of them. You ask the therapist about the disorder. Despite the impressive degrees hanging on her wall, she admits she’s never heard of it.
The hypothesis behind PANDAS, you learn, is that it is an autoimmune disorder caused when the antibodies that form to fight a common strep throat infection instead begin to attack the brain. The first step in treatment is to do a throat culture and specific type of blood test. If the results come back positive, the patient’s treatment begins with high doses of antibiotics. Meanwhile, when you do more Googling, you find a scary warning about some PANDAS patients having bad reactions to an anti-anxiety medication called Ativan, which just so happens to be something the consulting psychiatrist also recommended for your son.
In fury and desperation, you call the office of Dr. Denis Bouboulis, an immunologist in Darien, Connecticut, who has developed a reputation within the PANDAS community for providing aggressive, effective treatment. You beg for an appointment.
In the waiting room, you find patients from all over the country — even some from overseas. Sitting in another room, after a thorough examination, Bouboulis tells you he’s sure your boy has a “raging’’ case of the disorder. Then he tells you this: “You will get your son back.’’
It’s the first time you have felt hope since the nightmare began. You want to spring out of your chair and hug the man for his determination to rescue you and your boy from this frightening wilderness.
I know this case intimately because that boy is my nephew.
ONE OF THE SCARIEST PARTS about PANDAS is also what makes the diagnosis so controversial. Its trigger is the common strep infection, which is as reliable a part of the grade school experience as recess.
Dr. Robert Fuhlbrigge, a pediatric rheumatologist at Boston Children’s Hospital and associate professor at Harvard Medical School, puts it this way: “Virtually every child of school age gets strep every year.’’ If that seems impossible, consider that he’s including the many kids whose reaction to strep is mild enough that it is mistaken for the common cold. And he’s including the estimated 12 percent of schoolchildren who are carriers, meaning they aren’t bothered by streptococcal bacteria, yet can spread it to susceptible kids when they sneeze or cough.
Only those children who produce a positive throat culture are actually treated for strep. And the penicillin they get isn’t even for the fever and sore throat, which will usually go away in a few days. The antibiotic, Fuhlbrigge says, is primarily to guard against the very small risk that the strep infection will develop into rheumatic fever, and then rheumatic heart disease.
Though relatively uncommon in this country, rheumatic heart disease is rampant in the developing world. What causes it? Basically, the immune system gets confused. In trying to fight the strep bacteria, it mistakes a protein on the surface of heart valves for a similar looking protein on the surface of a strain of strep. Then it begins attacking the heart valves.
The idea behind PANDAS is that it works like rheumatic fever, except that rather than attacking the heart, the immune system goes after the brain. In the early 1990s, researchers at the National Institutes of Mental Health (NIMH) began studying whether infections could be behind acute-onset OCD in children. They focused on strep because it was the same bacteria behind an established neurological disorder called Syndenham chorea, where a portion of those who develop rheumatic fever begin to make involuntary, jerky movements. In 1998, a NIMH team led by Dr. Susan Swedo published clinical descriptions of 50 children whose sudden OCD and tic symptoms had been preceded by a strep infection.
Many researchers, including rheumatologists like Fuhlbrigge, saw promise in the hypothesis, because it followed the logic of rheumatic fever. Others, particularly neurologists, were dubious. Strep is so common that you’ll find it any classroom. Why not just argue that recess causes OCD?
The sniping in the medical field persisted for more than a decade, with subsequent studies unable to produce clear answers. Even Fuhlbrigge began to wonder whether Swedo had it right — the scientific evidence that strep causes OCD-like symptoms just wasn’t there. Childhood OCD, with its gradual onset, is fairly common — an estimated 1 percent to 3 percent of children have it. Fuhlbrigge and others came to suspect that PANDAS cases may simply be OCD children on the extreme end of the spectrum who respond particularly poorly to certain stressors, such as the stress caused by an infection.
Caught in the crossfire, meanwhile, were the families whose lives had been upended by the disorder, whatever its cause. In 2010, like some Cold War summit, the two sides convened at the National Institutes of Health. Swedo, by then chief of the NIMH’s pediatrics and developmental neuroscience branch, offered a major concession. She agreed to drop her exclusive focus on strep and accept that any number of infections — strep, flu, Lyme disease, or mycoplasma pneumonia (“walking pneumonia’’) — could trigger the autoimmune response that, in turn, triggered the OCD. The disorder was given a new, more encompassing handle, Pediatric Acute-onset Neuropsychiatric Syndrome, or PANS, with the sudden onset of symptoms being the distinguishing characteristic. (Mycoplasma, rather than strep, is believed to have been the trigger for my nephew’s PANS, based on the high levels of those antibodies in his blood.)
Swedo’s concessions were not enough. A couple of the neurologists at the conference insisted that PANDAS was a failed hypothesis and that the strep idea needed to be scrapped. Like Reagan and Gorbachev in Iceland, the two sides left this summit with long faces and pointed fingers.
One neurologist, Dr. Harvey Singer from Johns Hopkins, agreed to work with Swedo and other researchers on a PANS paper. But after Singer’s name appeared as the lead author with other neurologists on an anti-PANDAS paper published in the influential Journal of Pediatrics, Swedo dropped him from hers. She alleges that the neurologists downplayed the needs of parents and children in crisis, all so they can protect their standing as the only experts on the brain. She put aside her research for a while — it was too hard to “fight the naysayers,’’ she says — but the desperation of parents “pulled me back in.’’
Singer, meanwhile, faults Swedo for suggesting that there is an easy answer to explain and treat OCD and tics when, he argues, there is no good science to show that strep-triggered autoimmune PANDAS even exists.
Dr. Michele Casoli-Reardon is a child psychiatrist at North Shore Medical Center and an on-call specialist for MCPAP, the state’s referral service. With more than a decade of experience in treating PANDAS patients, she has tried to educate her fellow on-call psychiatrists as well as the front-line pediatricians. In her experience, some doctors steer clear of the diagnosis because of the contradictory medical literature. But many more, she argues, simply know nothing about it.
For Casoli-Reardon, PANDAS became even less of an abstraction when one of her sons developed it several years ago. She can identify with parents who find themselves completely unhinged by it. As for the critics from neurology, she says, “If you’ve ever had a child with PANDAS, you would never, ever say that it doesn’t exist.’’
THAT DISTINCTION may turn out to explain a lot about the battle.
Dr. James Leckman, a professor of child psychiatry at Yale and specialist in Tourette’s syndrome, was the lead author on what is perhaps the most persuasive study challenging the PANDAS hypothesis. That long-term study, published in 2011, found no compelling evidence linking the exacerbation of tic and OCD symptoms to new strep infections.
Yet Leckman tells me that in late 2008, well after all the patients had been enrolled in the study, he came to an astonishing realization: He and his coauthors had been studying the wrong children. Most of the kids in the study resembled those he regularly sees in his clinic — children with “garden-variety’’ Tourette’s and OCD. But after working with more physicians treating PANDAS patients, he had come to see firsthand that there was a distinct group of kids who literally had changed overnight, with dramatic onslaughts of OCD and other symptoms. And these “true’’ PANDAS/PANS cases weren’t represented in his study in any meaningful way.
Leckman says he lobbied his coauthors, who included Harvey Singer, to admit to this failing in their paper. But they refused, insisting they had followed the published PANDAS criteria in selecting their subjects. Leckman had to concede they were right — the children all met the criteria Swedo’s team had established. It’s just that he now believed those criteria were far too broad. So Leckman’s name was listed first on an influential paper that he felt was technically accurate but missed the larger point.
Nonetheless, Leckman had already become a changed man. Shortly after his epiphany, he says, “I picked up the phone and called Sue Swedo and told her that I had become a convert.’’
Leckman says he understands the resistance on the part of the neurologists. “True’’ overnight-onset OCD patients are rare and are far more likely to be seen by pediatricians, ER doctors, and psychiatrists than neurologists. Yet the neurologists are likely to have to deal with the fallout from PANDAS, seeing parents of kids with well-established conventional OCD who, after surfing the Web, appear in their office demanding antibiotics.
This intensifying standoff between traditional medicine and desperate parents has created what Harvard’s Fuhlbrigge calls “a public health crisis.’’ More than a year ago, Fuhlbrigge stopped accepting referrals of PANDAS patients to the rheumatology clinic at Boston Children’s Hospital. Given the lack of evidence for autoimmune disease in the patients he had seen and the confusion in the scientific literature, he felt he couldn’t do much for them and he needed to return his focus to rheumatology. Yet instead of adopting the nuanced approach he had taken earlier, others at Children’s Hospital have apparently pushed a much harder line against PANDAS.
Things came to a head this summer when parents of an 11-year-old girl who was being treated for PANS took her to Children’s because she was no longer eating. Maine lawyer and PANDAS activist Beth Maloney got involved in the case at the request of the parents. She alleges that specialists at Children’s insisted to the parents that PANDAS doesn’t exist and discontinued her antibiotics, arguing that the girl’s problems were entirely psychiatric. As relations worsened, she says, the hospital stationed security guards outside the girl’s room, presumably to prevent the parents from interfering with their daughter’s care.
The 11-year-old girl was eventually released, but, Maloney says, the pattern was repeated in early October. This time, the lawyer received a panicked call from a father who had learned that child protective services was going to court seeking temporary custody of his 16-year-old daughter. The girl had arrived at Children’s with a PANS diagnosis, which the attorney claims the Children’s doctors rejected. The next day, Maloney found herself standing before a Suffolk County judge. “What we have is an argument within the medical community about whether infection can cause behavioral disorders and mental health issues,’’ Maloney recalls saying. “And Boston Children’s Hospital is going to work that out on the backs of parents in your courtroom.’’
The judge, she says, granted the state temporary custody, although the parents have continued to have access to their daughter. Maloney, who wrote a book about her own son’s odyssey with PANDAS, acknowledges that this most recent patient does not fit the standard diagnostic requirement that symptoms show up before puberty. But she alleges the case reflects a wider hostility to the disorder at Children’s.
In a statement, the hospital rejected that allegation and similar complaints from parents about Children’s that have been lighting up PANS Internet message boards. “Boston Children’s treats hundreds of children a year displaying tics or obsessive or compulsive behaviors and other neuropsychiatric symptoms and always considers PANDAS/PANS as a potential diagnosis and provides care accordingly,’’ the statement read. “Among those patients, Boston Children’s has diagnosed and/or treated dozens of patients in the past year with PANS/PANDAS.’’
Even for those kids whose doctors accept PANS and who respond well to antibiotic treatment, that’s often not enough. While antibiotics can kill off a live infection and help prevent future ones, many patients have trouble getting back to base line. A more escalated form of treatment is called intravenous immunoglobulin, or IVIG, which is a blood product made up of filtered antibodies from a mix of more than a thousand adult blood donors. The idea behind giving it to PANS kids is that it can help “reset’’ the child’s immune system so that it stops attacking phantom threats in the brain.
IVIG has shown some promising results in PANS patients, but there has been no rigorous trial. It also comes with side effects such as nausea and headaches and a hefty price tag — about $10,000 a course — which many insurers refuse to pay. Yale’s Leckman is running a randomized trial of IVIG in conjunction with the NIMH. To avoid repeating his earlier mistake, Leckman is being exceedingly careful to enroll only “true’’ PANS patients. After screening more than 500 children, he and his colleagues have qualified fewer than 30.
Leckman expects to report results next year and hopes the study will help remove some of the murkiness around the disorder. The early signs have been encouraging, he says. But if the final results show that IVIG is ineffective, he will have no problem accepting that they need to look for a different treatment. Still, that won’t change his belief that PANS is real. “I am convinced these cases exist,’’ he says.
My nephew and his parents certainly agree. This past summer, six months after his troubles began and not long after he’d been put on a heavy dose of the antibiotic clarithromycin, his condition improved markedly. By now, many of his OCD behaviors have departed, and much of his old self has returned. His parents are hoping a course of IVIG treatment will bring him all the way back. They shudder to think what might have happened had they heeded the early advice to treat their son’s diagnosed anorexia with the tough-love, forced-eating approach recommended for an illness typically afflicting high school girls, rather than seeing it as a sign that their third-grade boy’s brain was under attack.
The neurologist critics are probably right: A good number of the parents who insist their kids have PANS might simply be seeking a socially acceptable antibiotic answer to what is more likely traditional (often inherited) OCD. But after witnessing my nephew’s ordeal and wading through the research, I’ve come to believe the neurologist critics are probably also wrong. There’s a subset of children who are truly affected overnight and genuinely different — the kind of kids who critic-turned-convert Leckman was big enough to admit he had previously missed.
I recognize I have a bias. But to me, shoehorning these particular kids into traditional treatment that is clearly failing them seems more than just insensitive. It seems indefensible.