By Shawne K. Wickham, Special to the Union Leader | Dec 20, 2024
Alexandra “Alex” Manfull was bright and beautiful, clever and creative, with a promising future ahead of her.
She was just 26 when she died, the victim of a mysterious illness that hijacked her brilliant mind and broke her parents’ hearts.
In the six years since Alex’s death, her parents, Susan and Bill “Towny” Manfull of Portsmouth, have devoted themselves to spreading awareness of, and research into, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus, commonly called PANDAS.
Since the death of their daughter, Alex, from PANDAS, Susan and Towny Manfull have devoted themselves to spreading awareness of the illness and encouraging research. Photo credit: Shawne K. Wickham
“We don’t want this to happen to another person or family,” Towny Manfull said.
The cute acronym belies the terrible nature of the illness. PANDAS and a related disorder, Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), are characterized by sudden-onset psychiatric symptoms, notably obsessive-compulsive disorder, tics and anxiety, following an infection such as strep throat or scarlet fever.
The bacteria that causes such infections can hide in the body by mimicking other molecules. Eventually, the body recognizes them as foreign, triggering an immune response. But the immune system also attacks the body’s own tissues, and when that includes the brain, it can set off neuro-psychiatric symptoms.
The disorder typically appears in childhood. But for Alex Manfull, it struck when she was in college.
“Our daughter was the center of our lives,” said Susan Manfull, a social psychologist. “She was a real force. From the very beginning, she had a personality that really lit up the room.”
As a child, Alex Manfull published a local newsletter in Portsmouth.Photo credit: Shawne K. Wickham
In elementary school, young Alex wrote and published a neighborhood newsletter, complete with local news and advertising. She won New Hampshire Public Television’s “Reading Rainbow” contest, and her story was animated and shown on television. She was interviewed by personality Don Imus on his radio show — twice.
“She had an awesome sense of humor and this big laugh,” Susan Manfull said. “She really was a very happy child.”
As Alex got older, her creativity only grew. A writer, artist and photographer, fluent in French, she attended Phillips Exeter Academy. The summer before college, she traveled to Jordan to study Arabic through a State Department program.
She came home from Jordan with strep throat, and was treated with antibiotics. Her parents weren’t worried.
Alex went on to Princeton University, where she was a coxswain on the crew team. In her sophomore year, she got mononucleosis and a second strep infection, and she seemed to be responding to the antibiotic treatment.
“But it was shortly after that, she began exhibiting symptoms that no one, including us, recognized as anything other than stress in college,” Susan Manfull said.
As a youngster, Alex Manfull was interviewed by radio personality Don Imus.Photo credit: Shawne K. Wickham
Beginning to understand
PANDAS/PANS is a continuum. Symptoms ebb and flow; they can be mild and then become incapacitating in what are called “flares,” Susan Manfull said.
And that’s what happened to Alex.
She began developing anxiety, insomnia and skin problems. What she didn’t tell her parents until later was that she was having symptoms of obsessive compulsive disorder, including counting her steps.
All this was affecting her schoolwork. She had trouble finishing long exams, and was late turning in papers.
Her parents now know that PANDAS accounts for everything Alex was experiencing.
“There’s a lot of symptoms that you have to connect the dots,” Towny Manfull said. “And today, very few clinicians have the skill or the experience to look at all these different symptoms and say, ‘Why did this start?’”
Alex was diagnosed with OCD and prescribed anti-anxiety medication. She graduated from college and moved to New York City, working as a financial analyst.
But her parents noticed changes in her personality. Their easy-going daughter easily became irritated. “She had a really short fuse. She was tired all the time because she didn’t sleep, but also she was working all those long hours,” her mother said.
Then Alex went to work for a hedge fund where, as part of her research, she came across some information about PANDAS.
Explanation at last
She called her parents. “She said, ‘I think I know what I have,’” Susan Manfull said. “I still remember it so vividly but I also remember thinking: PANDAS? Really?”
The name does a disservice, she now believes. Dartmouth Health, a leader in research and treatment, uses the term “neuro-immune psychiatric disorder,” and has established a clinic by that name, she said.
Alex was elated to have an explanation for her diverse, debilitating symptoms, Susan Manfull said. When Alex moved to Washington, D.C., she made an appointment with a neurologist who was very knowledgable about PANDAS, and who told Alex she was certain that’s what she was dealing with.
“Alex was thrilled, and she said, ‘When I get better, I’m going to tell everybody about this,’” she said. “We laughed about who was going to write the New Yorker article.”
The Manfulls had no idea how severe the illness can be, she said. “At the time there was just nothing in the literature about having these intrusive thoughts to take your life, or self-injurious types of behaviors.”
But one evening, Alex started texting Susan. She had been sick and had taken antibiotics, but she told her mom, “There’s something really wrong. This is really different.”
Susan promised to fly down the next day. She called Alex the next morning, but her daughter was upset and hung up on her, something she’d never done before. She tried to call Alex back, but there was no answer.
“I never talked to her again,” she said.
“We didn’t realize how unwell she was,” she said. “She ended up engaging in behaviors that took her life.”
They do not believe their daughter intended to harm herself. What makes them so sure?
“A lifetime of knowing this young woman,” Towny Manfull said. “This was not her. She was a fighter.”
“The day before this, she was looking forward to getting her treatment and changing the way people see this disorder.”
Acting on impulse
That morning, Alex had ordered a battery charger on Amazon and looked at a couch on Craig’s List. And a bag packed with equipment for a soccer league she had joined with work colleagues was sitting by the door. “So this was clearly something that came suddenly,” Towny Manfull said.
Susan Manfull displays a cherished keepsake, an illustrated story that her daughter Alex wrote in third grade that won New Hampshire Public Television’s “Reading Rainbow” contest.Photo credit: Shawne K. Wickham
Experts have since explained to the Manfulls that’s what can happen. “They have a flare and… they get these intrusive thoughts that tell them to take their lives,” Susan Manfull said. “They are so compelling that they can’t resist them and they act on them in an impulsive manner.”
“I’m positive that is what happened to her.”
They have talked with other parents with heartbreakingly similar stories. “There are young kids who end up dying because they listened to these intrusive thoughts,” Susan Manfull said.
Parents say the symptoms of PANDAS/PANS come on suddenly. “They put their child to bed and their child woke up a different person,” she said. “Or they come home from school and they are a drastically different person.”
The Manfulls have also talked with young people who have PANDAS. “Most of the time when they have these flares, they have no recollection of what happened,” Towny Manfull said. “It really is bypassing the executive level of the brain.”
“I think that’s the scariest part of this,” he said. “As a parent, it’s your worst fear.”
Alex’s legacy
Their only child’s sudden death galvanzied them to action. “If this can happen with Alex Manfull, this can happen to anybody,” Susan said.
They created the Alex Manfull Fund, which supports research into these disorders, produces a podcast and newsletter, and does legislative outreach. They sponsor symposiums for clinicians, researchers, advocates and policymakers to explore the latest treatment and diagnostic information.
The theme of a symposium they hosted last month was “Dialogue Saves Lives.” It takes a multi-disciplinary team to properly identify and treat this illness, Susan Manfull said.
One guest speaker, Dr. Richard Morse, a pediatric neurologist at Dartmouth Health Children’s, said the abrupt onset of OCD and tics is an important clue. “This is really lightning quick, over the course of a day, or two at the most,” he said.
The illness can progress to include mood disorders, behavioral regression, deterioration of cognitive functioning and suicidal ideation, Morse said, so early diagnosis can make a huge difference. Otherwise, he said, “It may end in great despair and a loss of a life.”
So much about these disorders remains a mystery, Towny Manfull said. “What we don’t know still today is why do some people get strep regularly and never have any adverse effect, and then other kids do have it,” he said. “So I think it’s still complicated, and we don’t have answers for that.”
And that’s why teaching medical and mental health providers to recognize the symptoms is so critical, his wife said. “If the infection and the immune system are not treated, you will continue to have this, and it will get worse and much more difficult to treat,” she said.
“Our vision is that no one else will ever lose their life, or lose years of their life … to find the right treatment,” she said.
At last month’s symposium, Susan Manfull invited the audience to “imagine a world without PANS and PANDAS.”
“I think that we will always have psychiatric symptoms, but imagine that we caught them early enough so that we diagnosed them early and they were treated effectively and resolved,” she said. “And the person with those symptoms can go back and live a healthy life.”
“We can do this,” Manfull said. “We can change the world. And we are here today to start that.”
Lupus has long been considered incurable—but a series of breakthroughs are fueling hope.
Illustration by The Atlantic. Sources: Jacopin / BSIP / Getty; Velimir Zeland / Shutterstock.
Lupus, doctors like to say, affects no two patients the same. The disease causes the immune system to go rogue in a way that can strike virtually any organ in the body, but when and where is maddeningly elusive. One patient might have lesions on the face, likened to wolf bites by the 13th-century physician who gave lupus its name. Another patient might have kidney failure. Another, fluid around the lungs. What doctors can say to every patient, though, is that they will have lupus for the rest of their life. The origins of autoimmune diseases like it are often mysterious, and an immune system that sees the body it inhabits as an enemy will never completely relax. Lupus cannot be cured. No autoimmune disease can be cured.
Two years ago, however, a study came out of Germany that rocked all of these assumptions. Five patients with uncontrolled lupus went into complete remission after undergoing a repurposed cancer treatment called CAR-T-cell therapy, which largely wiped out their rogue immune cells. The first treated patient has had no symptoms for almost four years now. “We never dared to think about the cure for our disease,” says Anca Askanase, a rheumatologist at Columbia University’s medical center who specializes in lupus. But these stunning results—remission in every patient—have fueled a new wave of optimism. More than 40 people with lupus worldwide have now undergone CAR-T-cell therapy, and most have gone into drug-free remission. It is too early to declare any of these patients cured for life, but that now seems within the realm of possibility.
Beyond lupus, doctors hope CAR-T portends a bigger breakthrough against autoimmune diseases, whose prevalence has been on a troubling rise. CAR-T has already been used experimentally to treat patients with other autoimmune diseases, including multiple sclerosis, myositis, and myasthenia gravis. And the success of CAR-T has inspired researchers to borrow other—cheaper and simpler—strategies from cancer therapy to kill immune cells gone awry. Not all of these ideas will pan out, but if any do, the next few years could bring an inflection point in treating some of the most frustrating and intractable diseases of our modern era.
CAR-T-cell therapy was originally developed as a way to kill malignant cells in blood cancer. It could, scientists later reasoned, also be used to kill specific white blood cells, called B cells, that go haywire with certain autoimmune diseases. One group tried a CAR-T-like therapy against an autoimmune disease called pemphigus vulgaris, and another CAR-T against lupus. It worked—but these experiments were only in mice.
This was the sum total of available scientific evidence when a 20-year-old woman came to her doctors in Erlangen, Germany, asking to try anything for her severe and uncontrolled lupus. None of the long-term medications typically used to manage lupus were working. Her kidneys, heart, and lungs were all failing, and she could walk only 30 feet by herself. CAR-T was risky, her doctor agreed, but lupus was killing her.
CAR-T-cell therapy could essentially turn her immune system against itself. First, doctors extracted from her blood a class of immune cells, called T cells, which they then engineered into chimeric antigen receptor T (CAR-T) cells that could recognize and destroy the B cells driving her lupus. CAR-T cells can cause dangerous and overwhelming inflammatory responses in cancer patients, and her doctors did worry that CAR-T could do the same for someone with autoimmune disease, whose immune system is already in overdrive. “We take the T cells out, activate them like crazy, and then shoot those massively overactivated T cells in an activated autoimmune disease. So if you think about it, that’s kind of crazy to do that, right?” says Fabian Müller, a hematologist-oncologist at the University Hospital of Erlangen and one of the doctors on the German team that pioneered the treatment. But fortunately, the woman with lupus did not have any serious side effects, nor did any of the other patients the German group has since dosed. They are all living their everyday lives, free of lupus symptoms and medications. The woman who could walk a mere 30 feet now runs five times a week, Müller told me. She’s gone back to school and is considering studying for a master’s in immunology.
Müller and his colleagues believe that CAR-T-cell therapy works by wiping out enough B cells to trigger a “deep reset” of the immune system. CAR-T cells are dogged little assassins; they are able to find and destroy even the B cells hiding deep in the body’s tissues. A patient’s B-cell count eventually recovers, but the new ones no longer erroneously attack the body itself. Cancer patients are sometimes considered “cured” after fiveyears of remission, and the first lupus patient to receive CAR-T is not so far off from that milestone. But the therapy cannot erase the genetic predisposition many patients have for the disease, says Donald Thomas, a rheumatologist in Maryland. Whether remission is actually durable enough to be a “cure” will take time to find out.
Still, these extraordinary results have set off a gold rush among biotech companies eager to solve autoimmune diseases. CAR-T start-ups founded to treat cancer are pivoting to target autoimmune diseases. And large pharmaceutical companies such as Bristol Myers Squibb, AstraZeneca, and Novartis are developing their own therapies. Columbia’s Askanase is now an investigator on five separate trials, all using CAR-T or a similar cellular therapy, and she hears from more companies all the time. There’s so much interest, she told me, “I don’t even know there are enough patients” to test new treatments. About 1.5 millionAmericans have lupus, but only a minority of them—those sick enough to justify experimental treatment but not so sick that they’ve suffered too much irreversible organ damage—are eligible for trials.
For now, CAR-T for lupus and other autoimmune diseases is pretty much only accessible in the U.S. through clinical trials—which, in effect, means it’s inaccessible to almost all lupus patients. Jonathan Greer, a rheumatologist in Florida, works in a seven-doctor practice that treats hundreds of people with lupus; not a single one has received CAR-T. He doesn’t know of a single center in Florida that is up and running to do these studies, so interested patients would have to travel out of state.
Even if it becomes FDA approved for autoimmune diseases, CAR-T is a long and expensive process. Because each patient’s own cells are reengineered, it cannot be easily scaled up. The cost of CAR-T for cancer runs about $500,000. Patients also need chemotherapy to kill existing T cells to make room for CAR- T, which adds risk, and in lupus, they usually need to taper off any medications keeping their disease in check, which can cause flare-ups. All these complications make the current iteration of CAR-T suitable only for lupus patients with severe disease, who have run out of other options.
The practical limitations of CAR-T have dogged the cancer field for a long time now, and researchers have already come up with ideas to get around it. A number of simpler strategies for killing B cells are now making their way from blood cancer to autoimmune disease. They include using donor T cells, a different type of immune cell called natural killer cells, or a molecule that binds a T cell to the B cell it’s meant to destroy. Those molecules, called bispecific T-cell engagers, or BiTEs, are “cheap, fast, uncomplicated,” Müller said, but they may not penetrate as deeply into the tissues where B cells reside. Nevertheless, in September, The New England Journal of Medicine published two successful casereports describing successful treatment in a handful of autoimmune diseases, including lupus, with a BiTE called teclistamab. Similar BiTES on the market could be repurposed for autoimmune disease too.
These simpler therapies may ultimately be “good enough,” Askanase said. And their ease of use could ultimately beat out custom CAR-T therapy, which is unlikely to reach all of the millions of people with lupus worldwide. It’s simply too expensive and too cumbersome, a problem that has held back other cutting-edgetherapies that were approved to much initial fanfare. Even if CAR-T itself is never widely adopted for autoimmune diseases, it has opened the door to new ideas that could one day revolutionize their treatment.
The Hoya • October 26, 2024 • https://thehoya.com/news/gumc-announces-new-pandas-pans-fellowship/
By Pritika Patel, Special to The Hoya
The Georgetown University Medical Center, in collaboration with the Alex Manfull Fund, which funds research on postinfection neuroimmune disorders, announced the launch of the new PANDAS/PANS Fellowship Fund Oct. 9.
The program is a four-year initiative designed to educate neuroimmunology fellows on pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS) — two autoimmune diseases — and how to identify their presence. The program will combine new research and clinical knowledge across disciplines, including otolaryngology, neurology, immunology and neuropathology, to equip future practitioners with the necessary skills to address the disorder effectively.
PANDAS and PANS are autoimmune diseases that follow an infection — most commonly a streptococcal infection — where the immune system attacks the body’s healthy brain cells, affecting central nervous system function. Despite their serious effects — including changes in personality, development of obsessive-compulsive disorder (OCD), anxiety, tics and in certain cases death — PANDAS and PANS often go unrecognized by health care providers due to the limited available research.
ELIZA MINEAUX/THE HOYA | The Georgetown University Medical Center and the Alex Manfull Fund, announced the launch of a new Fellowship Fund to study PANDAS/PANS, two autoimmune diseases.
Susan Manfull, co-founder and executive director of the Alex Manfull Fund, said the new program promises new discoveries.
“PANDAS/PANS is a multidisciplinary disorder and there are multiple systems involved in producing the symptoms that we see,” Manfull told The Hoya. “The fellowship fund is intended to set the stage for neurology students to work with other disciplines and develop cross-discipline relationships.”
Dr. Carlo Tornatore, the regional chief of neurology for Georgetown MedStar Health, said the program will better equip future healthcare professionals.
“The idea of the fellowship is training out the next generation of doctors who can think about the future,” Tornatore told The Hoya.
Daniela Sosa-Sarkar, board president of the Alex Manfull Fund, said PANDAS and PANS represent challenges in health care disparities with lack of insurance coverage.
“Insurance coverage is a huge problem for those suffering from PANDAS/PANS, which results at best in delayed treatment and at worst, lack of treatment and the devastating consequences that result,” Sosa-Sarkar told The Hoya. “The health inequities that result from lack of insurance coverage are real and devastating.”
Tornatore said he is optimistic about potential new discoveries the research will generate as well as its intersection with new technologies.
“I think we will make unexpected findings as we go along because we’re open,” Tornatore said. “I think over the next decade, we’re going to learn so much, especially with genomics, and AI is really going to explode how we understand.”
Manfull said further research into PANDAS and PANS is crucial for increasing awareness of the conditions among health care professionals and policymakers.
“If we can provide support to increase research, that research can compel doctors and insurance companies to understand that it is a truly serious disorder,” Manfull added.
The Alex Manfull Fund established Georgetown’s POND Brain Bank, the nation’s only brain bank which stores brains from individuals diagnosed with PANDAS, PANS and other neuroimmune disorders. The bank provides detailed neuropathological evaluations and oversees the procurement, storage and distribution of tissue and biofluids to researchers worldwide to discover biomarkers for PANDAS and PANS.
Sosa-Sarkar said Georgetown has been instrumental in helping study PANDAS, PANS and other diseases.
“Georgetown University has been an invaluable ally to the PANDAS/PANS community,” Sosa-Sarkar said. “Since the creation of the POND Bank, through the support of TAMF, and now The Alex Manfull PANDAS/PANS Fellowship Fund, Georgetown Medical Center has shown its commitment to advancing education and research on PANDAS/PANS.”
Manfull said the fund’s strength comes from its comprehensive approach to studying the disorder, promoting collaboration across medical departments and examining its various manifestations.
“Establishing The Alex Manfull PANDAS/PANS Fellowship Fund is truly visionary and demonstrates that the Department of Neurology at Georgetown embraces this new frontier in medicine,” Manfull said.
PORTSMOUTH — If you happened to cross over or view the World War I Memorial Bridge connecting Portsmouth and Kittery last week, you might have noticed that all of the bright lights had turned green. Over 200 bridges and landmarks around the world also turned green or red to shed light on PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) and a subcategory of PANS known as PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder w/Streptococcal Infections) Wednesday night.
PANS and PANDAS are such rare conditions that their symptoms are often overlooked or not properly interpreted by physicians and other practitioners. PANS can occur after a common infection that, in a small number of people, causes the body’s autoimmune system to mistakenly turn on the central nervous system. Sudden changes to a child’s personality can occur including obsessive-compulsive behaviors, anxiety, tics, abnormal movements, compromises to math and handwriting abilities, sensory sensitivities, restrictive eating, sleep disturbances and more. The PANDAS, a subcategory of PANS is triggered by a strep infection. Complex neurological and neuropsychiatric abnormalities subsequently ensue.
Locally, The Alex Manfull Fund seeks to drive increased awareness of these frightening conditions for the public and for medical practitioners who may encounter such rare and complex symptomologies. Susan and Towny Manfull of Portsmouth lost their 26-year-old daughter to PANDAS. Alex was a prolific artist in her preteen years, an accomplished scholar and graduate of Phillips Exeter Academy and Princeton. She made her young mark on Wall Street before pushing on to challenge Washington, D.C. Her life was full and full of many friends she met along the way. Despite all appearances, Alex’s achievements in life were being sadly undermined by PANDAS. Since her passing in 2018, Susan and Towny have been driven to make certain that other parents don’t share their tragedy. They have worked with local and national specialists who are keen on further understanding PANDAS and PANS, including the use of brain tissue from the POND Brain Bank at Georgetown University, a brain repository established when the Manfull’s donated their daughter’s brain. They started the Alex Manfull Fund. They have stocked their board with doctors and researchers knowledgeable in this highly specialized arena, and they have sought to attract supporters who know how to make a difference in the Seacoast community.
Among those supporters is Gov. Chris Sununu, who proclaimed that for New Hampshire Oct. 9 is a day where “it is imperative that there be a greater public awareness of this health issue, and more must be done to increase activity at the local, state, and national levels so that children can be more quickly diagnosed and treated.” A gathering of local supporters at the foot of the WWI Memorial Bridge Wednesday included Reverend Robert Thompson who addressed the crowd. Alex Manfull Fund board member Nancy Dougherty who is a Portsmouth-based Lyme disease specialist affiliated with Johns Hopkins Medical School also shared some of her knowledge of autoimmune afflictions with the vested concerned audience. Portsmouth City Councilors John Tabor and Kate Cook were on hand to lend personal support and that of their families. There was a heartfelt rendition of the national anthem led by Guilded Age and CODA actress Kayla Caulfield. Tears of joy were shed as the entire audience spontaneously joined Kayla.
Next up, The Alex Manfull Fund will be hosting its 2024 PANDA/PANS Symposium on Saturday, Nov. 2 at St. John’s Episcopal Church, 100 Chapel St. in Portsmouth from 9 a.m. to 5:30 p.m. This symposium is for physicians, psychologists, nurses and other health practitioners to advance the understanding and treatment of neuroimmune psychiatric disorders such as PANDAS and PANS.
Dr. Kyle Williams, a psychiatrist who specializes in OCD and PANDAS/PANS at Mass General Hospital in Boston, was in Portsmouth as a presenter for the November 2nd, 2024 PANDAS/PANS Symposium hosted by The Alex Manfull Fund.
Dr. Williams joined Susan Manfull, PhD at the WSCA FM Radio Station for what was an excellent interview with Kathy Somssich and Larry Drake.
A very informative must-listen-to for all followers of The Alex Manfull Fund.
In the final race of the 2023 Head of the Charles Regatta, one particular entry in the Directors’ Challenge Mixed Eight was comprised of a group that was rowing together for the very first time.
They represented different rowing backgrounds — including alumni from Phillips Exeter Academy, Princeton University, and members of the Boston Rowing Club — and were assembled from all over the United States.
Their unifying purpose, beyond pulling together in the race, was to honor the memory of a friend.
Alex Manfull, a New Hampshire native, was just 26 when she died in 2018 from complications of an autoimmune disorder called PANDAS (Pediatric AutoImmune Neuropsychiatric Disorders Associated with Streptococcal Infections). It is placed under the overarching category of PANS (Pediatric Acute Onset Neuropsychiatric Syndrome).
Manfull had attended Phillips Exeter, where she first discovered her talent as a coxswain with the crew program.
“She took to it like a fish to water, and loved it, loved being a coxswain,” recalled her mother, Susan.
Manfull went on to attend Princeton, where she coxed for the men’s varsity lightweight crew.
“She was very assertive and driven and focused both in crew and outside of that,” recalled Andrew Wenstein, who rowed in boats that Manfull was coxswain for at both Phillips Exeter and Princeton.
“She was very good at just getting people to kind of trust her and listen to her,” he said.
“Alex was vibrant, healthy, had no history of psychiatric illness,” her mother recalled. “She was healthy in general, confident, smart, all the qualities that one would aspire to have.”
At the age of 19, she was diagnosed with streptococcus. Soon after being treated, she developed “unambiguous OCD symptoms.”
For years afterward, Manfull sought a clearer medical explanation of what was happening to her, but the exact nature of her condition remained unclear. It wasn’t until she came upon a description of PANDAS that she began to unravel the mystery herself.
Even then, Manfull did not receive a formal diagnosis until several weeks before her death.
“The lack of knowledgeable physicians or other medical providers and mental health providers is a huge obstacle because the disorder is not usually recognized,” Susan explained. “It’s frequently misdiagnosed as OCD, or ADHD. And when that happens, of course they don’t get the treatment that they should.”
Given that PANDAS wasn’t first identified until 1998 (in a study from Dr. Susan Swedo), the problem of misdiagnoses remains intrinsically connected with a lack of awareness.
As a result, Manfull’s parents established The Alex Manfull Fund to help support research, treatment, and to elevate public knowledge about its identifiable symptoms.
In the ongoing effort to raise awareness, they decided that assembling a representative entry at this year’s Head of Charles was a way to achieve that goal at an event their daughter loved.
Testament to her spirit, current and former rowers from around the country answered the call.
“We started thinking about doing this about a year and a half ago, and it took a while to kind of figure out all of the logistics and pull it together,” said Wenstein. “She was on teams at Exeter and at Princeton and at Boston Rowing Club in the summer in between. So it felt like we should have people from a few different areas of the rowing world.”
The final result was a respectable 14th place among the 31 Directors’ Challenge entries. Considering their lack of preparation, it was a job well done. And of infinitely greater importance, the Manfull Fund, both through its participation in the race as well as a tent at Reunion Village, was able to help share information about PANDAS/PANS and provide access to experts.
Doctors are uniting to find a cure for Pandas, a disorder that arrives ‘like the flick of a switch’ and torments children as young as three
Louise Eccles | Sunday May 05 2024, 12.01am BST, The Sunday Times
Oliver spent his 14th birthday last month alone in his bedroom, as he has done for the past four years. He did not unwrap a single present and ate his special birthday food alone in the kitchen, late at night, when he knew his mother and sister would be upstairs.
Until the age of nine, he was a sociable, high-achieving boy who was head of his school council. His Year 5 report described him as a popular member of the class and a dedicated learner.
In January 2020, however, he returned home from primary school unusually quiet and withdrawn. When his mother, Megan, checked on him in his bedroom that night, she said it was “literally like a switch had been flipped”.
“He had stripped down to his shorts and he was just rocking in the middle of the room with a fan on him, in the middle of winter, with the window open. He was wailing and saying his skin was hot. He was petrified of falling asleep. He went psychotic overnight.”
Oliver still cannot bear any form of human contact, or even face-to-face conversations. He communicates from the top of the staircase. He has not left the house for two years, since his last hospital admission, and wears no clothes except a blanket.
Having baffled medical professionals for 18 months, Oliver was eventually given a diagnosis of paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, or Pandas, by a neurologist at Birmingham Children’s Hospital.
Hope of treatment
Pandas specifically refers to children who have developed symptoms after contracting streptococcus, which can manifest as scarlet fever, tonsillitis and other conditions.
The charity Pans Pandas UK believes thousands of children could be affected nationwide, but no official figures are collated. Pans refers to the broader condition that can be triggered by other causes.
Professor Rajat Gupta, the consultant paediatric neurologist at Birmingham Children’s Hospital who diagnosed Oliver’s condition in October 2021, said he had diagnosed Pans or Pandas in approximately 100 children. He called for the medical profession to keep an open mind. “Children presenting like this may have a cause which could be easily treated with a short course of antibiotics of two weeks,” he said.
A working group of neurologists, immunologists and paediatricians has been formed to try to come to a national consensus on how to diagnose and treat Pandas, including whether antibiotics or anti-inflammatory drugs should be prescribed alongside psychiatric help.
Conclusions reached by the group will be presented to the National Institute for Health and Care Excellence (Nice), which advises the NHS on best practice. The group includes representatives from the Royal College of Psychiatrists, the Royal College of Paediatrics and Child Health, the Royal College of Nursing and the Royal College of Occupational Therapists.
‘She was clawing at her mum and screaming’
The parents of a schoolgirl who suffered a sudden mental breakdown in November 2021 credited the quick action of a GP for their daughter’s return to health.
Ellie, 13, had been poorly with a sore throat, like several of her friends, but her parents treated her with Calpol and assumed she had recovered.
Her father, Nick, the director of a design company, said: “She left for school in the morning a confident, well-adjusted girl with a great friendship group, and when she returned from school she was experiencing a full panic attack. She was clawing at her mum and screaming, ‘Make it stop’.
“It emerged she was having intrusive thoughts that she might harm herself. She was scared she was going to go into the kitchen drawer and pick up a knife and plunge it into her chest.”
Over the next few days, Ellie developed a tic where she would clear her throat constantly. “She hardly slept because she was worried she would harm herself,” Nick said. “Her age seemed to regress and she played almost toddler-level games with cars. Her pupils were so dilated they were like Disney eyes.”
Nick found the Pans Pandas UK charity website and read about children taking antibiotics to treat an underlying infection.
“We went to the locum GP and she hadn’t heard of Pandas, but she was open-minded. She said, ‘well, I see no issue with trialling a couple of weeks worth of antibiotics while we set up blood tests and refer you to the local hospital’. Within three days the symptoms went from 100 per cent to 25 per cent.”
After Ellie tested positive for historic streptococcus, the same GP prescribed three months of antibiotics. Cognitive behaviour therapy helped to deal with the residual intrusive thoughts and she has now fully recovered.
Self-teaching at home
Unlike many other mental health conditions, Pandas — a term coined in the United States in 1998 — has been linked to unusual symptoms including urinary issues, dramatic loss of skills such as handwriting and unexpected development of special educational needs.
Oliver’s father, Ben, a financial adviser, said. “I remember him just howling like a wild animal in the back of the car and he tried to jump out. He was screaming, ‘Let me die, let me die’.” He was initially diagnosed with an autistic breakdown and treated with anti-psychotic drugs.
Months later, after his mother stumbled across Pandas while researching his condition and raised it with a psychiatrist, Oliver was referred to a neurologist.
Since then he has been prescribed a combination of antibiotics, anti-inflammatory drugs and therapy. Today, he is enrolled at a school that he has never attended. Megan said staff visited regularly but were “at a loss” about what to do. Oliver teaches himself subjects such as politics and history from his bedroom.
Megan said: “He’s starting to come out of it. He even talks about the fact that it’s going to be over at some point, so I think he’s coming back into the world.”
No concrete signs
Dr Ming Lim, a consultant paediatric neurologist at Evelina London Children’s Hospital, who sits on the new working group, said one of the reasons Pandas was controversial was because there was no concrete biomarker, such as a brain scan or blood test, to confirm someone had the condition.
“This is a very peculiar, very recognisable, acute-onset neuropsychiatric syndrome. What I don’t know is why [it occurs], biologically. There is some research into brain inflammation going on.”
Fulvio D’Acquisto, professor of immunology at the University of Roehampton, said Pandas may be caused by an overactive immune response leading to the accumulation in the brain of a protein called Immuno-moodulin. He has an antibody in development that he says could block the protein.
A spokesman for Nice said: “As an organisation, we do not have sufficient resources to create evidence-based guidance for all topics in health and care, and an element of selection is therefore required.” NHS England said it welcomed the work that Pans Pandas UK was conducting with professional bodies to advance research.
The names of all children and parents have been changed
In recent years, the intricate connection between mental and physical health has become increasingly apparent. A groundbreaking study, published in The Economist, sheds light on the profound impact of bodily triggers on various mental health conditions. Contrary to conventional wisdom, which often siloed mental and physical health, this research unveils a complex interplay, where bodily processes serve as potent catalysts for mental health manifestations.
Drawing from a wealth of empirical evidence and clinical insights, the article explores how diverse mental health conditions, ranging from anxiety disorders to depression, are intricately linked to bodily triggers. These triggers encompass an array of physiological phenomena, including inflammation, hormonal imbalances, and gut microbiome composition. By elucidating these connections, the research not only challenges prevailing perceptions but also paves the way for a holistic approach to mental healthcare.
Furthermore, the study underscores the imperative of interdisciplinary collaboration, advocating for a synthesis of medical specialties traditionally segregated. Through an integrative lens, clinicians can decipher the intricate web of causality, offering tailored interventions that address both mental and physical aspects of health. This paradigm shift not only enhances treatment efficacy but also fosters a more nuanced understanding of mental health, rooted in the intricate dance between mind and body.
Ultimately, this article heralds a new era in mental health discourse, one that transcends traditional boundaries and embraces the interconnectedness of human health. By acknowledging the pivotal role of bodily triggers, it catalyzes a transformative shift in how we perceive, diagnose, and treat mental health conditions, heralding a more comprehensive and compassionate approach to healing.
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Posted: December 22, 2024 by bmanfull@comcast.net
PANDAS: A cute name for a terrible illness that claimed a beautiful life
By Shawne K. Wickham, Special to the Union Leader | Dec 20, 2024
Alexandra “Alex” Manfull was bright and beautiful, clever and creative, with a promising future ahead of her.
She was just 26 when she died, the victim of a mysterious illness that hijacked her brilliant mind and broke her parents’ hearts.
In the six years since Alex’s death, her parents, Susan and Bill “Towny” Manfull of Portsmouth, have devoted themselves to spreading awareness of, and research into, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus, commonly called PANDAS.
“We don’t want this to happen to another person or family,” Towny Manfull said.
The cute acronym belies the terrible nature of the illness. PANDAS and a related disorder, Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), are characterized by sudden-onset psychiatric symptoms, notably obsessive-compulsive disorder, tics and anxiety, following an infection such as strep throat or scarlet fever.
The bacteria that causes such infections can hide in the body by mimicking other molecules. Eventually, the body recognizes them as foreign, triggering an immune response. But the immune system also attacks the body’s own tissues, and when that includes the brain, it can set off neuro-psychiatric symptoms.
The disorder typically appears in childhood. But for Alex Manfull, it struck when she was in college.
“Our daughter was the center of our lives,” said Susan Manfull, a social psychologist. “She was a real force. From the very beginning, she had a personality that really lit up the room.”
In elementary school, young Alex wrote and published a neighborhood newsletter, complete with local news and advertising. She won New Hampshire Public Television’s “Reading Rainbow” contest, and her story was animated and shown on television. She was interviewed by personality Don Imus on his radio show — twice.
“She had an awesome sense of humor and this big laugh,” Susan Manfull said. “She really was a very happy child.”
As Alex got older, her creativity only grew. A writer, artist and photographer, fluent in French, she attended Phillips Exeter Academy. The summer before college, she traveled to Jordan to study Arabic through a State Department program.
She came home from Jordan with strep throat, and was treated with antibiotics. Her parents weren’t worried.
Alex went on to Princeton University, where she was a coxswain on the crew team. In her sophomore year, she got mononucleosis and a second strep infection, and she seemed to be responding to the antibiotic treatment.
“But it was shortly after that, she began exhibiting symptoms that no one, including us, recognized as anything other than stress in college,” Susan Manfull said.
Beginning to understand
PANDAS/PANS is a continuum. Symptoms ebb and flow; they can be mild and then become incapacitating in what are called “flares,” Susan Manfull said.
And that’s what happened to Alex.
She began developing anxiety, insomnia and skin problems. What she didn’t tell her parents until later was that she was having symptoms of obsessive compulsive disorder, including counting her steps.
All this was affecting her schoolwork. She had trouble finishing long exams, and was late turning in papers.
Her parents now know that PANDAS accounts for everything Alex was experiencing.
“There’s a lot of symptoms that you have to connect the dots,” Towny Manfull said. “And today, very few clinicians have the skill or the experience to look at all these different symptoms and say, ‘Why did this start?’”
Alex was diagnosed with OCD and prescribed anti-anxiety medication. She graduated from college and moved to New York City, working as a financial analyst.
But her parents noticed changes in her personality. Their easy-going daughter easily became irritated. “She had a really short fuse. She was tired all the time because she didn’t sleep, but also she was working all those long hours,” her mother said.
Then Alex went to work for a hedge fund where, as part of her research, she came across some information about PANDAS.
Explanation at last
She called her parents. “She said, ‘I think I know what I have,’” Susan Manfull said. “I still remember it so vividly but I also remember thinking: PANDAS? Really?”
The name does a disservice, she now believes. Dartmouth Health, a leader in research and treatment, uses the term “neuro-immune psychiatric disorder,” and has established a clinic by that name, she said.
Alex was elated to have an explanation for her diverse, debilitating symptoms, Susan Manfull said. When Alex moved to Washington, D.C., she made an appointment with a neurologist who was very knowledgable about PANDAS, and who told Alex she was certain that’s what she was dealing with.
“Alex was thrilled, and she said, ‘When I get better, I’m going to tell everybody about this,’” she said. “We laughed about who was going to write the New Yorker article.”
The Manfulls had no idea how severe the illness can be, she said. “At the time there was just nothing in the literature about having these intrusive thoughts to take your life, or self-injurious types of behaviors.”
But one evening, Alex started texting Susan. She had been sick and had taken antibiotics, but she told her mom, “There’s something really wrong. This is really different.”
Susan promised to fly down the next day. She called Alex the next morning, but her daughter was upset and hung up on her, something she’d never done before. She tried to call Alex back, but there was no answer.
“I never talked to her again,” she said.
“We didn’t realize how unwell she was,” she said. “She ended up engaging in behaviors that took her life.”
They do not believe their daughter intended to harm herself. What makes them so sure?
“A lifetime of knowing this young woman,” Towny Manfull said. “This was not her. She was a fighter.”
“The day before this, she was looking forward to getting her treatment and changing the way people see this disorder.”
Acting on impulse
That morning, Alex had ordered a battery charger on Amazon and looked at a couch on Craig’s List. And a bag packed with equipment for a soccer league she had joined with work colleagues was sitting by the door. “So this was clearly something that came suddenly,” Towny Manfull said.
Experts have since explained to the Manfulls that’s what can happen. “They have a flare and… they get these intrusive thoughts that tell them to take their lives,” Susan Manfull said. “They are so compelling that they can’t resist them and they act on them in an impulsive manner.”
“I’m positive that is what happened to her.”
They have talked with other parents with heartbreakingly similar stories. “There are young kids who end up dying because they listened to these intrusive thoughts,” Susan Manfull said.
Parents say the symptoms of PANDAS/PANS come on suddenly. “They put their child to bed and their child woke up a different person,” she said. “Or they come home from school and they are a drastically different person.”
The Manfulls have also talked with young people who have PANDAS. “Most of the time when they have these flares, they have no recollection of what happened,” Towny Manfull said. “It really is bypassing the executive level of the brain.”
“I think that’s the scariest part of this,” he said. “As a parent, it’s your worst fear.”
Alex’s legacy
Their only child’s sudden death galvanzied them to action. “If this can happen with Alex Manfull, this can happen to anybody,” Susan said.
They created the Alex Manfull Fund, which supports research into these disorders, produces a podcast and newsletter, and does legislative outreach. They sponsor symposiums for clinicians, researchers, advocates and policymakers to explore the latest treatment and diagnostic information.
The theme of a symposium they hosted last month was “Dialogue Saves Lives.” It takes a multi-disciplinary team to properly identify and treat this illness, Susan Manfull said.
One guest speaker, Dr. Richard Morse, a pediatric neurologist at Dartmouth Health Children’s, said the abrupt onset of OCD and tics is an important clue. “This is really lightning quick, over the course of a day, or two at the most,” he said.
The illness can progress to include mood disorders, behavioral regression, deterioration of cognitive functioning and suicidal ideation, Morse said, so early diagnosis can make a huge difference. Otherwise, he said, “It may end in great despair and a loss of a life.”
So much about these disorders remains a mystery, Towny Manfull said. “What we don’t know still today is why do some people get strep regularly and never have any adverse effect, and then other kids do have it,” he said. “So I think it’s still complicated, and we don’t have answers for that.”
And that’s why teaching medical and mental health providers to recognize the symptoms is so critical, his wife said. “If the infection and the immune system are not treated, you will continue to have this, and it will get worse and much more difficult to treat,” she said.
“Our vision is that no one else will ever lose their life, or lose years of their life … to find the right treatment,” she said.
At last month’s symposium, Susan Manfull invited the audience to “imagine a world without PANS and PANDAS.”
“I think that we will always have psychiatric symptoms, but imagine that we caught them early enough so that we diagnosed them early and they were treated effectively and resolved,” she said. “And the person with those symptoms can go back and live a healthy life.”
“We can do this,” Manfull said. “We can change the world. And we are here today to start that.”
Posted: November 11, 2024 by bmanfull@comcast.net
A ‘Crazy’ Idea for Treating Autoimmune Diseases Might Actually Work
Sarah Zhang
Lupus has long been considered incurable—but a series of breakthroughs are fueling hope.
Lupus, doctors like to say, affects no two patients the same. The disease causes the immune system to go rogue in a way that can strike virtually any organ in the body, but when and where is maddeningly elusive. One patient might have lesions on the face, likened to wolf bites by the 13th-century physician who gave lupus its name. Another patient might have kidney failure. Another, fluid around the lungs. What doctors can say to every patient, though, is that they will have lupus for the rest of their life. The origins of autoimmune diseases like it are often mysterious, and an immune system that sees the body it inhabits as an enemy will never completely relax. Lupus cannot be cured. No autoimmune disease can be cured.
Two years ago, however, a study came out of Germany that rocked all of these assumptions. Five patients with uncontrolled lupus went into complete remission after undergoing a repurposed cancer treatment called CAR-T-cell therapy, which largely wiped out their rogue immune cells. The first treated patient has had no symptoms for almost four years now. “We never dared to think about the cure for our disease,” says Anca Askanase, a rheumatologist at Columbia University’s medical center who specializes in lupus. But these stunning results—remission in every patient—have fueled a new wave of optimism. More than 40 people with lupus worldwide have now undergone CAR-T-cell therapy, and most have gone into drug-free remission. It is too early to declare any of these patients cured for life, but that now seems within the realm of possibility.
Beyond lupus, doctors hope CAR-T portends a bigger breakthrough against autoimmune diseases, whose prevalence has been on a troubling rise. CAR-T has already been used experimentally to treat patients with other autoimmune diseases, including multiple sclerosis, myositis, and myasthenia gravis. And the success of CAR-T has inspired researchers to borrow other—cheaper and simpler—strategies from cancer therapy to kill immune cells gone awry. Not all of these ideas will pan out, but if any do, the next few years could bring an inflection point in treating some of the most frustrating and intractable diseases of our modern era.
CAR-T-cell therapy was originally developed as a way to kill malignant cells in blood cancer. It could, scientists later reasoned, also be used to kill specific white blood cells, called B cells, that go haywire with certain autoimmune diseases. One group tried a CAR-T-like therapy against an autoimmune disease called pemphigus vulgaris, and another CAR-T against lupus. It worked—but these experiments were only in mice.
This was the sum total of available scientific evidence when a 20-year-old woman came to her doctors in Erlangen, Germany, asking to try anything for her severe and uncontrolled lupus. None of the long-term medications typically used to manage lupus were working. Her kidneys, heart, and lungs were all failing, and she could walk only 30 feet by herself. CAR-T was risky, her doctor agreed, but lupus was killing her.
CAR-T-cell therapy could essentially turn her immune system against itself. First, doctors extracted from her blood a class of immune cells, called T cells, which they then engineered into chimeric antigen receptor T (CAR-T) cells that could recognize and destroy the B cells driving her lupus. CAR-T cells can cause dangerous and overwhelming inflammatory responses in cancer patients, and her doctors did worry that CAR-T could do the same for someone with autoimmune disease, whose immune system is already in overdrive. “We take the T cells out, activate them like crazy, and then shoot those massively overactivated T cells in an activated autoimmune disease. So if you think about it, that’s kind of crazy to do that, right?” says Fabian Müller, a hematologist-oncologist at the University Hospital of Erlangen and one of the doctors on the German team that pioneered the treatment. But fortunately, the woman with lupus did not have any serious side effects, nor did any of the other patients the German group has since dosed. They are all living their everyday lives, free of lupus symptoms and medications. The woman who could walk a mere 30 feet now runs five times a week, Müller told me. She’s gone back to school and is considering studying for a master’s in immunology.
Müller and his colleagues believe that CAR-T-cell therapy works by wiping out enough B cells to trigger a “deep reset” of the immune system. CAR-T cells are dogged little assassins; they are able to find and destroy even the B cells hiding deep in the body’s tissues. A patient’s B-cell count eventually recovers, but the new ones no longer erroneously attack the body itself. Cancer patients are sometimes considered “cured” after five years of remission, and the first lupus patient to receive CAR-T is not so far off from that milestone. But the therapy cannot erase the genetic predisposition many patients have for the disease, says Donald Thomas, a rheumatologist in Maryland. Whether remission is actually durable enough to be a “cure” will take time to find out.
Still, these extraordinary results have set off a gold rush among biotech companies eager to solve autoimmune diseases. CAR-T start-ups founded to treat cancer are pivoting to target autoimmune diseases. And large pharmaceutical companies such as Bristol Myers Squibb, AstraZeneca, and Novartis are developing their own therapies. Columbia’s Askanase is now an investigator on five separate trials, all using CAR-T or a similar cellular therapy, and she hears from more companies all the time. There’s so much interest, she told me, “I don’t even know there are enough patients” to test new treatments. About 1.5 million Americans have lupus, but only a minority of them—those sick enough to justify experimental treatment but not so sick that they’ve suffered too much irreversible organ damage—are eligible for trials.
For now, CAR-T for lupus and other autoimmune diseases is pretty much only accessible in the U.S. through clinical trials—which, in effect, means it’s inaccessible to almost all lupus patients. Jonathan Greer, a rheumatologist in Florida, works in a seven-doctor practice that treats hundreds of people with lupus; not a single one has received CAR-T. He doesn’t know of a single center in Florida that is up and running to do these studies, so interested patients would have to travel out of state.
Even if it becomes FDA approved for autoimmune diseases, CAR-T is a long and expensive process. Because each patient’s own cells are reengineered, it cannot be easily scaled up. The cost of CAR-T for cancer runs about $500,000. Patients also need chemotherapy to kill existing T cells to make room for CAR- T, which adds risk, and in lupus, they usually need to taper off any medications keeping their disease in check, which can cause flare-ups. All these complications make the current iteration of CAR-T suitable only for lupus patients with severe disease, who have run out of other options.
The practical limitations of CAR-T have dogged the cancer field for a long time now, and researchers have already come up with ideas to get around it. A number of simpler strategies for killing B cells are now making their way from blood cancer to autoimmune disease. They include using donor T cells, a different type of immune cell called natural killer cells, or a molecule that binds a T cell to the B cell it’s meant to destroy. Those molecules, called bispecific T-cell engagers, or BiTEs, are “cheap, fast, uncomplicated,” Müller said, but they may not penetrate as deeply into the tissues where B cells reside. Nevertheless, in September, The New England Journal of Medicine published two successful case reports describing successful treatment in a handful of autoimmune diseases, including lupus, with a BiTE called teclistamab. Similar BiTES on the market could be repurposed for autoimmune disease too.
These simpler therapies may ultimately be “good enough,” Askanase said. And their ease of use could ultimately beat out custom CAR-T therapy, which is unlikely to reach all of the millions of people with lupus worldwide. It’s simply too expensive and too cumbersome, a problem that has held back other cutting-edge therapies that were approved to much initial fanfare. Even if CAR-T itself is never widely adopted for autoimmune diseases, it has opened the door to new ideas that could one day revolutionize their treatment.
Updated: October 30, 2024 by bmanfull@comcast.net
Alex Manfull Fund Announces New Board Members with Strong Advocacy Ties
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Updated: October 30, 2024 by bmanfull@comcast.net
GUMC Announces New PANDAS/PANS Fellowship
The Hoya • October 26, 2024 • https://thehoya.com/news/gumc-announces-new-pandas-pans-fellowship/
By Pritika Patel, Special to The Hoya
The Georgetown University Medical Center, in collaboration with the Alex Manfull Fund, which funds research on postinfection neuroimmune disorders, announced the launch of the new PANDAS/PANS Fellowship Fund Oct. 9.
The program is a four-year initiative designed to educate neuroimmunology fellows on pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS) — two autoimmune diseases — and how to identify their presence. The program will combine new research and clinical knowledge across disciplines, including otolaryngology, neurology, immunology and neuropathology, to equip future practitioners with the necessary skills to address the disorder effectively.
PANDAS and PANS are autoimmune diseases that follow an infection — most commonly a streptococcal infection — where the immune system attacks the body’s healthy brain cells, affecting central nervous system function. Despite their serious effects — including changes in personality, development of obsessive-compulsive disorder (OCD), anxiety, tics and in certain cases death — PANDAS and PANS often go unrecognized by health care providers due to the limited available research.
Susan Manfull, co-founder and executive director of the Alex Manfull Fund, said the new program promises new discoveries.
“PANDAS/PANS is a multidisciplinary disorder and there are multiple systems involved in producing the symptoms that we see,” Manfull told The Hoya. “The fellowship fund is intended to set the stage for neurology students to work with other disciplines and develop cross-discipline relationships.”
Dr. Carlo Tornatore, the regional chief of neurology for Georgetown MedStar Health, said the program will better equip future healthcare professionals.
“The idea of the fellowship is training out the next generation of doctors who can think about the future,” Tornatore told The Hoya.
Daniela Sosa-Sarkar, board president of the Alex Manfull Fund, said PANDAS and PANS represent challenges in health care disparities with lack of insurance coverage.
“Insurance coverage is a huge problem for those suffering from PANDAS/PANS, which results at best in delayed treatment and at worst, lack of treatment and the devastating consequences that result,” Sosa-Sarkar told The Hoya. “The health inequities that result from lack of insurance coverage are real and devastating.”
Tornatore said he is optimistic about potential new discoveries the research will generate as well as its intersection with new technologies.
“I think we will make unexpected findings as we go along because we’re open,” Tornatore said. “I think over the next decade, we’re going to learn so much, especially with genomics, and AI is really going to explode how we understand.”
Manfull said further research into PANDAS and PANS is crucial for increasing awareness of the conditions among health care professionals and policymakers.
“If we can provide support to increase research, that research can compel doctors and insurance companies to understand that it is a truly serious disorder,” Manfull added.
The Alex Manfull Fund established Georgetown’s POND Brain Bank, the nation’s only brain bank which stores brains from individuals diagnosed with PANDAS, PANS and other neuroimmune disorders. The bank provides detailed neuropathological evaluations and oversees the procurement, storage and distribution of tissue and biofluids to researchers worldwide to discover biomarkers for PANDAS and PANS.
Sosa-Sarkar said Georgetown has been instrumental in helping study PANDAS, PANS and other diseases.
“Georgetown University has been an invaluable ally to the PANDAS/PANS community,” Sosa-Sarkar said. “Since the creation of the POND Bank, through the support of TAMF, and now The Alex Manfull PANDAS/PANS Fellowship Fund, Georgetown Medical Center has shown its commitment to advancing education and research on PANDAS/PANS.”
Manfull said the fund’s strength comes from its comprehensive approach to studying the disorder, promoting collaboration across medical departments and examining its various manifestations.
“Establishing The Alex Manfull PANDAS/PANS Fellowship Fund is truly visionary and demonstrates that the Department of Neurology at Georgetown embraces this new frontier in medicine,” Manfull said.
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Posted: October 23, 2024 by bmanfull@comcast.net
Lighting Up for PANDAS/PANS
Community News
Published October 22, 2024
PORTSMOUTH — If you happened to cross over or view the World War I Memorial Bridge connecting Portsmouth and Kittery last week, you might have noticed that all of the bright lights had turned green. Over 200 bridges and landmarks around the world also turned green or red to shed light on PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) and a subcategory of PANS known as PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder w/Streptococcal Infections) Wednesday night.
PANS and PANDAS are such rare conditions that their symptoms are often overlooked or not properly interpreted by physicians and other practitioners. PANS can occur after a common infection that, in a small number of people, causes the body’s autoimmune system to mistakenly turn on the central nervous system. Sudden changes to a child’s personality can occur including obsessive-compulsive behaviors, anxiety, tics, abnormal movements, compromises to math and handwriting abilities, sensory sensitivities, restrictive eating, sleep disturbances and more. The PANDAS, a subcategory of PANS is triggered by a strep infection. Complex neurological and neuropsychiatric abnormalities subsequently ensue.
Locally, The Alex Manfull Fund seeks to drive increased awareness of these frightening conditions for the public and for medical practitioners who may encounter such rare and complex symptomologies. Susan and Towny Manfull of Portsmouth lost their 26-year-old daughter to PANDAS. Alex was a prolific artist in her preteen years, an accomplished scholar and graduate of Phillips Exeter Academy and Princeton. She made her young mark on Wall Street before pushing on to challenge Washington, D.C. Her life was full and full of many friends she met along the way. Despite all appearances, Alex’s achievements in life were being sadly undermined by PANDAS. Since her passing in 2018, Susan and Towny have been driven to make certain that other parents don’t share their tragedy. They have worked with local and national specialists who are keen on further understanding PANDAS and PANS, including the use of brain tissue from the POND Brain Bank at Georgetown University, a brain repository established when the Manfull’s donated their daughter’s brain. They started the Alex Manfull Fund. They have stocked their board with doctors and researchers knowledgeable in this highly specialized arena, and they have sought to attract supporters who know how to make a difference in the Seacoast community.
Among those supporters is Gov. Chris Sununu, who proclaimed that for New Hampshire Oct. 9 is a day where “it is imperative that there be a greater public awareness of this health issue, and more must be done to increase activity at the local, state, and national levels so that children can be more quickly diagnosed and treated.” A gathering of local supporters at the foot of the WWI Memorial Bridge Wednesday included Reverend Robert Thompson who addressed the crowd. Alex Manfull Fund board member Nancy Dougherty who is a Portsmouth-based Lyme disease specialist affiliated with Johns Hopkins Medical School also shared some of her knowledge of autoimmune afflictions with the vested concerned audience. Portsmouth City Councilors John Tabor and Kate Cook were on hand to lend personal support and that of their families. There was a heartfelt rendition of the national anthem led by Guilded Age and CODA actress Kayla Caulfield. Tears of joy were shed as the entire audience spontaneously joined Kayla.
Next up, The Alex Manfull Fund will be hosting its 2024 PANDA/PANS Symposium on Saturday, Nov. 2 at St. John’s Episcopal Church, 100 Chapel St. in Portsmouth from 9 a.m. to 5:30 p.m. This symposium is for physicians, psychologists, nurses and other health practitioners to advance the understanding and treatment of neuroimmune psychiatric disorders such as PANDAS and PANS.
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Updated: October 30, 2024 by bmanfull@comcast.net
Advancing Research & Treatment for Neuroimmune Psychiatric Disorders: PANDAS/PANS 2024 Symposium in Portsmouth, NH
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Updated: October 7, 2024 by bmanfull@comcast.net
Radio Interview with Dr. Kyle Williams and Susan Manfull, PhD on WSCA’s Seacoast Currents
Dr. Kyle Williams, a psychiatrist who specializes in OCD and PANDAS/PANS at Mass General Hospital in Boston, was in Portsmouth as a presenter for the November 2nd, 2024 PANDAS/PANS Symposium hosted by The Alex Manfull Fund.
Dr. Williams joined Susan Manfull, PhD at the WSCA FM Radio Station for what was an excellent interview with Kathy Somssich and Larry Drake.
A very informative must-listen-to for all followers of The Alex Manfull Fund.
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Posted: July 1, 2024 by bmanfull@comcast.net
Head of the Charles entry came together to honor late Phillips Exeter coxswain
The Directors’ Challenge entry, assembled from around the country, rowed together in memory Alex Manfull and to help raise awareness of PANDAS/PANS.
By Hayden Bird
October 24, 2023
In the final race of the 2023 Head of the Charles Regatta, one particular entry in the Directors’ Challenge Mixed Eight was comprised of a group that was rowing together for the very first time.
They represented different rowing backgrounds — including alumni from Phillips Exeter Academy, Princeton University, and members of the Boston Rowing Club — and were assembled from all over the United States.
Their unifying purpose, beyond pulling together in the race, was to honor the memory of a friend.
Alex Manfull, a New Hampshire native, was just 26 when she died in 2018 from complications of an autoimmune disorder called PANDAS (Pediatric AutoImmune Neuropsychiatric Disorders Associated with Streptococcal Infections). It is placed under the overarching category of PANS (Pediatric Acute Onset Neuropsychiatric Syndrome).
Manfull had attended Phillips Exeter, where she first discovered her talent as a coxswain with the crew program.
“She took to it like a fish to water, and loved it, loved being a coxswain,” recalled her mother, Susan.
Manfull went on to attend Princeton, where she coxed for the men’s varsity lightweight crew.
“She was very assertive and driven and focused both in crew and outside of that,” recalled Andrew Wenstein, who rowed in boats that Manfull was coxswain for at both Phillips Exeter and Princeton.
“She was very good at just getting people to kind of trust her and listen to her,” he said.
“Alex was vibrant, healthy, had no history of psychiatric illness,” her mother recalled. “She was healthy in general, confident, smart, all the qualities that one would aspire to have.”
At the age of 19, she was diagnosed with streptococcus. Soon after being treated, she developed “unambiguous OCD symptoms.”
For years afterward, Manfull sought a clearer medical explanation of what was happening to her, but the exact nature of her condition remained unclear. It wasn’t until she came upon a description of PANDAS that she began to unravel the mystery herself.
Even then, Manfull did not receive a formal diagnosis until several weeks before her death.
“The lack of knowledgeable physicians or other medical providers and mental health providers is a huge obstacle because the disorder is not usually recognized,” Susan explained. “It’s frequently misdiagnosed as OCD, or ADHD. And when that happens, of course they don’t get the treatment that they should.”
Given that PANDAS wasn’t first identified until 1998 (in a study from Dr. Susan Swedo), the problem of misdiagnoses remains intrinsically connected with a lack of awareness.
As a result, Manfull’s parents established The Alex Manfull Fund to help support research, treatment, and to elevate public knowledge about its identifiable symptoms.
In the ongoing effort to raise awareness, they decided that assembling a representative entry at this year’s Head of Charles was a way to achieve that goal at an event their daughter loved.
Testament to her spirit, current and former rowers from around the country answered the call.
“We started thinking about doing this about a year and a half ago, and it took a while to kind of figure out all of the logistics and pull it together,” said Wenstein. “She was on teams at Exeter and at Princeton and at Boston Rowing Club in the summer in between. So it felt like we should have people from a few different areas of the rowing world.”
The final result was a respectable 14th place among the 31 Directors’ Challenge entries. Considering their lack of preparation, it was a job well done. And of infinitely greater importance, the Manfull Fund, both through its participation in the race as well as a tent at Reunion Village, was able to help share information about PANDAS/PANS and provide access to experts.
Updated: May 10, 2024 by bmanfull@comcast.net
‘Let me die’: the mysterious syndrome changing children overnight
Doctors are uniting to find a cure for Pandas, a disorder that arrives ‘like the flick of a switch’ and torments children as young as three
Louise Eccles | Sunday May 05 2024, 12.01am BST, The Sunday Times
Oliver spent his 14th birthday last month alone in his bedroom, as he has done for the past four years. He did not unwrap a single present and ate his special birthday food alone in the kitchen, late at night, when he knew his mother and sister would be upstairs.
Until the age of nine, he was a sociable, high-achieving boy who was head of his school council. His Year 5 report described him as a popular member of the class and a dedicated learner.
In January 2020, however, he returned home from primary school unusually quiet and withdrawn. When his mother, Megan, checked on him in his bedroom that night, she said it was “literally like a switch had been flipped”.
“He had stripped down to his shorts and he was just rocking in the middle of the room with a fan on him, in the middle of winter, with the window open. He was wailing and saying his skin was hot. He was petrified of falling asleep. He went psychotic overnight.”
Oliver still cannot bear any form of human contact, or even face-to-face conversations. He communicates from the top of the staircase. He has not left the house for two years, since his last hospital admission, and wears no clothes except a blanket.
Having baffled medical professionals for 18 months, Oliver was eventually given a diagnosis of paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, or Pandas, by a neurologist at Birmingham Children’s Hospital.
Hope of treatment
Pandas specifically refers to children who have developed symptoms after contracting streptococcus, which can manifest as scarlet fever, tonsillitis and other conditions.
The charity Pans Pandas UK believes thousands of children could be affected nationwide, but no official figures are collated. Pans refers to the broader condition that can be triggered by other causes.
Professor Rajat Gupta, the consultant paediatric neurologist at Birmingham Children’s Hospital who diagnosed Oliver’s condition in October 2021, said he had diagnosed Pans or Pandas in approximately 100 children. He called for the medical profession to keep an open mind. “Children presenting like this may have a cause which could be easily treated with a short course of antibiotics of two weeks,” he said.
A working group of neurologists, immunologists and paediatricians has been formed to try to come to a national consensus on how to diagnose and treat Pandas, including whether antibiotics or anti-inflammatory drugs should be prescribed alongside psychiatric help.
Conclusions reached by the group will be presented to the National Institute for Health and Care Excellence (Nice), which advises the NHS on best practice. The group includes representatives from the Royal College of Psychiatrists, the Royal College of Paediatrics and Child Health, the Royal College of Nursing and the Royal College of Occupational Therapists.
‘She was clawing at her mum and screaming’
The parents of a schoolgirl who suffered a sudden mental breakdown in November 2021 credited the quick action of a GP for their daughter’s return to health.
Ellie, 13, had been poorly with a sore throat, like several of her friends, but her parents treated her with Calpol and assumed she had recovered.
Her father, Nick, the director of a design company, said: “She left for school in the morning a confident, well-adjusted girl with a great friendship group, and when she returned from school she was experiencing a full panic attack. She was clawing at her mum and screaming, ‘Make it stop’.
“It emerged she was having intrusive thoughts that she might harm herself. She was scared she was going to go into the kitchen drawer and pick up a knife and plunge it into her chest.”
Over the next few days, Ellie developed a tic where she would clear her throat constantly. “She hardly slept because she was worried she would harm herself,” Nick said. “Her age seemed to regress and she played almost toddler-level games with cars. Her pupils were so dilated they were like Disney eyes.”
Nick found the Pans Pandas UK charity website and read about children taking antibiotics to treat an underlying infection.
“We went to the locum GP and she hadn’t heard of Pandas, but she was open-minded. She said, ‘well, I see no issue with trialling a couple of weeks worth of antibiotics while we set up blood tests and refer you to the local hospital’. Within three days the symptoms went from 100 per cent to 25 per cent.”
After Ellie tested positive for historic streptococcus, the same GP prescribed three months of antibiotics. Cognitive behaviour therapy helped to deal with the residual intrusive thoughts and she has now fully recovered.
Self-teaching at home
Unlike many other mental health conditions, Pandas — a term coined in the United States in 1998 — has been linked to unusual symptoms including urinary issues, dramatic loss of skills such as handwriting and unexpected development of special educational needs.
Oliver’s father, Ben, a financial adviser, said. “I remember him just howling like a wild animal in the back of the car and he tried to jump out. He was screaming, ‘Let me die, let me die’.” He was initially diagnosed with an autistic breakdown and treated with anti-psychotic drugs.
Months later, after his mother stumbled across Pandas while researching his condition and raised it with a psychiatrist, Oliver was referred to a neurologist.
Since then he has been prescribed a combination of antibiotics, anti-inflammatory drugs and therapy. Today, he is enrolled at a school that he has never attended. Megan said staff visited regularly but were “at a loss” about what to do. Oliver teaches himself subjects such as politics and history from his bedroom.
Megan said: “He’s starting to come out of it. He even talks about the fact that it’s going to be over at some point, so I think he’s coming back into the world.”
No concrete signs
Dr Ming Lim, a consultant paediatric neurologist at Evelina London Children’s Hospital, who sits on the new working group, said one of the reasons Pandas was controversial was because there was no concrete biomarker, such as a brain scan or blood test, to confirm someone had the condition.
“This is a very peculiar, very recognisable, acute-onset neuropsychiatric syndrome. What I don’t know is why [it occurs], biologically. There is some research into brain inflammation going on.”
Fulvio D’Acquisto, professor of immunology at the University of Roehampton, said Pandas may be caused by an overactive immune response leading to the accumulation in the brain of a protein called Immuno-moodulin. He has an antibody in development that he says could block the protein.
A spokesman for Nice said: “As an organisation, we do not have sufficient resources to create evidence-based guidance for all topics in health and care, and an element of selection is therefore required.” NHS England said it welcomed the work that Pans Pandas UK was conducting with professional bodies to advance research.
The names of all children and parents have been changed
Updated: May 5, 2024 by bmanfull@comcast.net
Many mental-health conditions have bodily triggers
Science and technology | Brain vs body
Full Article:
https://bit.ly/44vYGe5
Abstract (ChatGPT):
In recent years, the intricate connection between mental and physical health has become increasingly apparent. A groundbreaking study, published in The Economist, sheds light on the profound impact of bodily triggers on various mental health conditions. Contrary to conventional wisdom, which often siloed mental and physical health, this research unveils a complex interplay, where bodily processes serve as potent catalysts for mental health manifestations.
Drawing from a wealth of empirical evidence and clinical insights, the article explores how diverse mental health conditions, ranging from anxiety disorders to depression, are intricately linked to bodily triggers. These triggers encompass an array of physiological phenomena, including inflammation, hormonal imbalances, and gut microbiome composition. By elucidating these connections, the research not only challenges prevailing perceptions but also paves the way for a holistic approach to mental healthcare.
Furthermore, the study underscores the imperative of interdisciplinary collaboration, advocating for a synthesis of medical specialties traditionally segregated. Through an integrative lens, clinicians can decipher the intricate web of causality, offering tailored interventions that address both mental and physical aspects of health. This paradigm shift not only enhances treatment efficacy but also fosters a more nuanced understanding of mental health, rooted in the intricate dance between mind and body.
Ultimately, this article heralds a new era in mental health discourse, one that transcends traditional boundaries and embraces the interconnectedness of human health. By acknowledging the pivotal role of bodily triggers, it catalyzes a transformative shift in how we perceive, diagnose, and treat mental health conditions, heralding a more comprehensive and compassionate approach to healing.