Teen’s Unique Web-Design Fundraising Strategy Aids Companies and Nonprofits

Rare Daily, by Global Genes
(Editor) Ilana Jacqueline is the Managing Editor of The RARE Daily at Global Genes. She assists the patient community…


The Greenville, South Carolina native had a unique idea for how to raise funds for her favorite charities. In exchange for a $1000 donation, she would offer companies a complete website for their business.

“I took a web design class in my freshman and sophomore years,” said Butenhoff. “And for the past two summers I’ve been building sites for work as a summer job.”

She started raising money for an organization called PAALS, a service dog nonprofit. She had a personal connection with the organization as they provided her with Sami, her own service dog. Butenhoff suffers from two diseases–Ehlers Danlos Syndrome and Postural Orthostatic Tachycardia Syndrome.

Now she’s working on expanding her altruistic reach.

“When I became a client of PAALS, my family and I wanted to raise $25,000 and through everything that I have been involved in – we have passed that goal,” says Butenhoff. ” With my organization, Made By Mer – I’m hoping to build at least one site for each charity I’m supporting in the next 6 months, raising $1,000 for each of them.  Maybe my site will generate donations as well.”

It’s an ambitious goal, as she says each site, depending on variables can take her anywhere from four to eight weeks to complete.

She has now included Global Genes in her register of organizations her clients can donate to. Find out more about Meredith on her website here: www.madebymer.com


See all of Ilana Jacqueline's Posts

Ehlers-Danlos Syndrome Hypermobility Type: A Genetic Predisposition to the Development of Various Functional Somatic Syndromes

The Pain Relief Foundation
March 11, 2015

Tea Lynn Moore
Pain Conditions


Functional Somatic Syndromes, conditions characterized by functional disability and self reported symptoms rather than clearly demonstrable organic problems, are a common contemporary health issue [1]. Each medical subspecialty seems to have at least one somatic syndrome for patients whose symptoms cannot otherwise be medically explained. These include: irritable bowel syndrome (gastroenterology); fibromyalgia (rheumatology); tension headaches (neurology); and chronic fatigue syndrome (immunology) [2]. In recent years, however, a significant portion of these patients have gone on to receive a diagnoses of a little known connective tissue disorder: Ehlers-Danlos syndrome hypermobility type (EDS-HT), formerly type III [3]. In this literature review, I will discuss the features of EDS-HT, explore EDS-HT as a possible unifying concept for various functional somatic syndromes, illuminate further implications of the described findings, outline a set of diagnostic criteria that should be implemented by healthcare professionals in functional diagnostic medicine, and propose a novel way of thinking about functional somatic syndromes.

Ehlers-Danlos Hypermobility Type (EDS-HT) Overview

 EDS-HT, considered to be one and the same with joint hypermobility syndrome (JHS), is a relatively common, frequently underdiagnosed heritable condition which predisposes those afflicted to chronic, widespread musculoskeletal pain and a wide variety of articular and extra-articular features purportedly linked to constitutionally abnormal collagen. The diagnosis is primarily clinical in essence and is largely based on the Beighton score (a simple system used to quantify joint laxity and hypermobility) and medical history. It is predominantly of autosomal dominant inheritance, though the molecular basis of EDS-HT is still largely unknown except for a minority of patients mutated in TNXB and COL3A1 [4]. Skin biopsies may show alterations in collagen fibril morphology [5]. Early literature fixed the frequency of EDS as a whole to 1 in 5000, with EDS-HT accounting for approximately half of all registered cases. However, due to it’s vast underdiagnosis, a presumed frequency of 0.75-2% has been proposed for EDS-HT [4].

Hypermobility and the Autonomic Nervous System:
The Missing Link for Various Functional Somatic Syndromes

When first described, EDS-HT was considered to be a relatively benign condition, with acute and chronic joint instabilities as it’s unique clinical consequence. Recently, however, accumulated experience on the management of EDS-HT patients elucidated a more complex clinical picture. In particular, subjects with joint hypermobility appear to be more prone to developing a range of functional somatic syndromes [3], including fibromyalgia [6], chronic fatigue syndrome [7], headaches [8], complex regional pain syndrome [10], gastrointestinal functional disorder [11], pelvic organ prolapse [12], and orthostatic intolerance [13].

An underlying dysautonomic process may explain many of the aforementioned functional somatic syndromes seen in EDS-HT individuals, which are present in practically all major body systems. Leading research suggests that the pathogenic relationship between dysautonomia and congenital laxity of the connective tissue is primarily attributable to the pathological deformation of the brainstem and upper spinal cord from occipitoatlantoaxial hypermobility and cranial settling [8]. In other words, craniocervical hypermobility and instability, and the resulting deformative stress of repetitive stretching and ventral brainstem compression, appear to underlie the observed autonomic dysfunction in hypermobile patients [9]. As demonstrated in pathological reports of fatal cases of traumatic brain injury and numerous animal studies, repetitive stretching of nerves can lead to clumping and loss of neurofilaments and microtubules within the axon and promotes neural apoptosis [14][15]. Strain also alters the electro-chemistry of the nerve by decreasing the amplitude of action potentials [16] and increasing calcium influx into the cell [17]. When you apply this research to the context of hypermobile individuals, the underlying process of autonomic nervous system dysfunction becomes palpable. Unsurprisingly, the histopathological changes in neural axons that are undergone in these situations would not show up on any routine diagnostic test. In extreme cases, however, cranial settling and a reduction of the clivo-axial angle may be demonstrable on MRIs, but typically only when imaged in the upright position [8]. This would explain why many of these patients’ diagnostic imaging reports state negative results.

In accord with craniocervical hypermobility findings, recent studies have suggested that up to 70% of patients with hypermobility have orthostatic intolerance and other forms of dysautonomia. The orthostatic effect in EDS-HT individuals may also be compounded by abnormal connective tissue in the vasculature, which results in an increase in blood vessel distensibility in response to the augmented hydrostatic pressure that occurs during orthostatic stress. This leads to exaggerated blood pooling in the lower extremities with a resultant tachycardia [18]. While these findings were predictable, a reversed frequency study, wherein hypermobility was measured in patients diagnosed with Postural Orthostatic Tachycardia Syndrome, a prevalent form of dysautonomia in young people, found that an extraordinary 53% of participants met the diagnostic criteria for EDS-HT [19]. Furthermore, when hypermobility was measured in individuals diagnosed with Chronic Fatigue Syndrome, a condition with a longstanding, established association with orthostatic intolerance [20], researchers found that 25% of Chronic Fatigue syndrome sufferers had generalized hypermobility [21]. This phenomena, though, is likely of multifactorial consequence, as dysautonomia, chronic pain, and sleep apnea secondary to ventral brainstem compression can result in poor sleep architecture and chronic fatigue [22][23][24].

Ehlers-Danlos Syndrome Hypermobility Type as a Systemic Condition

 The autonomic nervous system problems associated with hypermobility, alike various functional somatic disorders, are present in practically all major body systems. In the realm of gastroenterology, for instance, dysautonomia in the form of vagus nerve damage (which may result from craniocervical instability) can result in delayed gastric emptying [25] and affect bowel contractibility, causing nausea and the so called “irritable bowl syndrome” [26]. Moreover, the underlying collagen abnormality of EDS-HT itself is systemic. Insufficient collagen may reduce sphincter tone and increase distensibility of the gut wall (which is likely to influence the function of surrounding cellular mechano-receptors), resulting in decreased gastrointestinal motility, gastroesophageal reflux (GERD) and/or irritable bowel syndrome (IBS). In fact, over 50% of EDS-HT individuals have GERD and/or IBS [4][27]. When hypermobility was tested in patients diagnosed with functional gastrointestinal disorders (which include IBS, functional dyspepsia, and functional constipation), an astonishing 49% were found to have joint hypermobility and many of those patients went on to receive an official diagnosis of EDS-HT [10].

When it comes to neurological manifestations, headaches are among the most common complaint in the EDS-HT population [4]. As a consequence of occipitoatlantoaxial hypermobility, drooping of the cerebellar tonsils and obstruction of the cerebrospinal flow at the craniocervical junction can result in intracranial pressure [8][28]. In addition, rapid fluctuations in blood pressure and inadequate cerebral perfusion on upright posture caused by dysautonomia may lead to migraines [29][30]. People with lax joints are also predisposed to cerviocogenic, tension, and new daily persistent headaches arising from musculoskeletal dysfunction in the temporal mandibular joints and the upper three cervical segments of the spine [4][31].

As a consequence of ligamentous laxity, rheumatological complications among the EDS-HT population are commonplace. Chronic pain in patients with joint hypermobility stems from a predisposition to injury from daily minor trauma to the joints and ligaments [32]. Unstable joints may also lead to frequent dislocations, subluxations, sprains, and stretch injury to the nerves traversing hypermobile joints, further increasing the risk of developing chronic pain states such as arthralgia, repetitive strain injuries, and complex regional pain syndrome [4][9][33]. There is also a high incidence of muscular pain attributable to myofacial spasms. Tender points consistent with fibromyalgia are often palpable, especially in the paravertebral musculature [34]. In frequency studies, the prevalence of fibromyalgia in EDS-HT participants was established to be 30% [35] and the prevalence of EDS-HT among fibromyalgia subjects was found to be 27.3% [6]. One theory for the origin of pain in fibromyalgia ascribes it to excessive muscle stress, which may increase the excitability of nociceptive ends of the muscle [36][37]. Joint instability in hyperlax individuals may result in sustained muscle stress (an overcompensation mechanism for loose and injured joints) and over stimulation of nociceptive nerve endings (which are poorly supported by defective collagen fibrils) [38]. An alternative, although equivocal, theory has suggested that biomechanical disturbances in the cervical spine may play a role in the pathogenesis of fibromyalgia. In a controlled study of 161 cases of traumatic injury to the cervical spine (primarily “whiplash”), fibromyalgia was diagnosed in 21.6% of those with neck injury verses 1.7% control subjects with lower extremity fractures [39], bringing us back to the notion that craniocervical instability, and the subsequent neurological damage, may be the underlying process in the development of functional somatic syndromes.

Further Implications of Discussed Findings in the Diagnosis and Management of Functional Somatic Syndromes

 These observations suggest that a careful examination for hypermobility and connective tissue abnormalities should be an integral part of functional diagnostic medicine. Pathological deformation of the brainstem and stretch injury to neural axons due to an underlying congenital ligamentous laxity, as discussed here in the case of EDS-HT, or acquired ligamentous instability, such as whiplash, may indeed be the missing link in the pathogenesis of various functional somatic syndromes.

In a literature review of functional somatic syndromes, Wessely and colleges concluded, “a substantial overlap exists between the individual syndromes and that the similarities between them outweigh the differences” and “patients with one syndrome frequently meet diagnostic criteria for another” [40]. For this subset of patients, generalized joint hypermobility may represent the common milieu for functional somatic syndromes with ubiquitous manifestations. The predispositions EDS-HT imposes would further explain why many of these patients are affected profoundly by emotional arousal (as it’s mediated by the autonomic nervous system) and muscle tension, and why patients with different syndromes share non-symptom characteristics such as sex (as joint laxity is more pronounced in females) and develops at a relatively young age (as EDS-HT is heritable, and hence, lifelong) [4][41].

Accordingly, articular hypermobility can be assessed by using the 9-point Beighton score, which assigns one point for each side of the body on which the patient can (1) passively dorsiflex the 5th finger >90 degrees with the forearm flat on the table, (2) passively appose the thumb to the flexor aspect of the forearm, (3) hyperextend the elbow beyond 10 degrees, and (4) hyperextend the knee beyond 10 degrees and one point for forward flexion of the trunk with the legs straight so that the palms rest flat on the floor. If a patient receives a Beighton score of 4 or more, a referral to a geneticist or rheumatologist for further evaluation is recommended [42]. If cranial settling and a reduction in the clivo-axial angle is suspected, and upright MRI may additionally aid in diagnosis [8].

With this hitherto unobserved connection comes a new line of treatment for a subdivision of patients with functional somatic disorders. Physical therapy, in the form of exercises that strengthen joint-supporting muscles, and bracing may provide joint stability and help minimize articular injury [4]. Elimination of brainstem deformation by straightening and stabilizing the craniocervical junction (via fusion surgery) may also improve pain, neural functioning, and quality of life [8].

Conclusion: A Paradigm Shift in the Etiology of Functional Somatic Syndromes

Disorders that lack “objective markers” are usually considered to be functional, not “organic.” This implies to some that the symptoms in functional somatic syndromes are physiological manifestations of psychosocial factors, a view that enforces an insular attitude to the etiology of disease rather than an interactive holistic approach. Consequently, when investigative results are negative, management is commonly limited to reassurance about the (apparent) absence of disease and occasionally psychiatric therapy. These treatments, however, are unpopular with patients, have low coherence rates, and seldom provide long-term therapeutic relief [41][43].

An alternative explanation is that the organic abnormalities are undetectable through cursory diagnostic testing as the underlying mechanism may be histopathological in origin, or, as seen in the case of upright MRIs on EDS-HT patients, the body may not be in the problematic position when testing takes place. The overly common cognitive error overshadowing high-tech medicine –that emotional issues are the underpinnings of illnesses lacking objectivity– must be overcome. While it is sufficient to say that, like virtually all known illnesses, psychosocial factors do play some role in functional somatic syndromes [1], an over emphasis on medically unexplained symptoms as being psychological bases causal reasoning on a negative. An absence of evidence does not denote an absence of organic disease –it simply means that the conditions that were tested for are not present in the individual and there is an infinite realm of alternative possibilities, such as EDS-HT.

Functional somatic disorders can only be successfully managed in the healthcare setting once a comprehensive understanding of their nature and treatment is acquired. The recognition of Ehlers-Danlos Syndrome Hypermobility type, and other disorders involving ligamentous laxity, as a possible physiological mechanism underlying various medically unexplained symptoms will help bridge the gap in physicians’ minds between described physical complaints and apparent negative test results in a subset of patients. Henceforth, in the wake of this disclosed correlation, further investigation into the role hypermobility and connective tissue abnormalities play in the etiology of these conditions, alongside a redefinition and modification of the diagnostic criteria of functional somatic syndromes, is essential to study of medically unexplained phenomena.



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WINGS group offers help to Penn State students with disabilities

PENN State News
By Jim Carlson

April 14, 2015

Maria Walls knew she would encounter some difficult times when she enrolled at Penn State in 2013. She didn’t know exactly what they would be. She didn’t know when and where they would occur. But the Arlington, Virginia, resident and rehabilitation and human services (RHS) major in the College of Education did know why problems would ensue.

Walls’ day-to-day life is impaired by two disabilities -- gastroparesis, a paralysis of the stomach tract and intestines, and Postural Orthostatic Tachycardia Syndrome (POTS), an autonomous nervous disorder as well as a circulatory condition. 

On a campus as large as University Park, Walls knew those conditions would catch up with her and slow her down. She said exhaustion and fatigue are constants; weakness, dizziness and nausea also often plague her.

"So it was hard to walk around on such a big campus and get acclimated," Walls said. "The environment here is very fast-paced. Just adjusting to days where I’m awake for 18 hours and hardly getting any sleep, it was a lot to kind of navigate my way through.’’

Because she knew she wasn’t alone -- even though one’s inner feelings to that end can be prevalent -- she navigated her way to the Office of Disability Services (ODS) and floated the idea of a student organization called WINGS.

The term is not an acronym. The mantra of the club, she told ODS, would be to soar over disabilities. “I said, ‘you know what, I hear you guys don’t have a program like this and I think there’s a need for it at this university. I would like to start it and I need your help.’

“I kind of asserted lot of authority there but it worked out,’’ she said.

WINGS, officially named a student organization in 2014, is up to nearly 35 members.

“There were a lot of struggles that I was going through and throughout all that I felt like I wished I had some people who understood what I was going through,’’ Walls said. “People who I could form relationships with and draw support from and give them my support as well.’

“It pretty much came from me recognizing that there are a lot of students at the school who have disabilities but they just don’t know where to find each other.’’

Wendy Coduti, an assistant professor within RHS, said that rates of students with disabilities attending college have increased each year. “Which is a great thing as it reflects increased access to education as well as increased diversity on campuses,’’ she said.

“For students with disabilities, there may also be a concern around stigma and ‘what will people think if they find out I have a disability?’ WINGS helps students with disabilities connect and find peers who have gone through similar situations,’’ Coduti said.

“I think WINGS will help other students with disabilities realize that there are many other students here at Penn State who also have a disability -- both visible and invisible -- and WINGS is a great way for students to connect.’’

Keith Jervis, director of the Office of Disability Services at Penn State, said about 1,600 students with disabilities have registered at University Park and another 1,600 students among the commonwealth campuses. That amounts to 3.5 percent of the student population, he said, a figure that is in line with what Penn State’s Big Ten partners report.

“There is a level of comfort in speaking with a fellow student who is having a shared experience that can’t be replicated in our office,’’ Jervis said. “We hope that through these connections (in WINGS) students will be informed of our services; in particular, our initiatives with corporate partners to increase employment opportunities for individuals with disabilities.’’

It took nearly three years of medical testing but Walls finally was diagnosed during her junior year of high school. Accepting it was no brief time frame, either.

“Honestly I think it’s probably something I still struggle with but it took me about a year and a half to really understand and see myself as a person with a disability and really realize there were changes that needed to be made in order for me to move forward,’’ Walls said.

“I think once I was able to do that then I really took control of what I needed to do to live a life with a disability. But I think the personal adjustment process and acceptance was very, very difficult for me.’’

She said her mother was -- and still is -- her rock, and that “a big extended family’’ also offered care whenever needed; she deemed herself fortunate.

Walls wanted others to feel equally fortunate. She’s encountered WINGS members who have multiple sclerosis, intellectual disabilities, those with depression and anxiety and even some with POTS, which is her affliction.

“Privacy is a big thing for us so disclosure of a disability is not necessary,’’ she said. “It’s a club that is designed to where you get out of it as much as you put into it. Anybody can be as involved or uninvolved as they like. One of the most beneficial parts of the club is just getting students with disabilities to meet one another,’’ she said.

Walls received cooperation from Coduti and Jason Gines, assistant professor in counselor education and RHS. “My RHS professors have really inspired the fire inside of me and the passion to pursue this career,’’ Walls said. “They just make it seem so attainable and make it seem like such a wonderful thing and something that I want to be a part of.’’

Two years remain before Walls becomes a part of the Class of 2017 job market. Though starting off as a criminology major, once she took the little steps to form WINGS, she simultaneously was taking bigger steps toward her RHS career.

“I realized that working with people with disabilities is my passion, it’s what I want to do, it’s what feels right to me,’’ she said. “All I know is I want to be working directly with people who have disabilities because I think that’s where I thrive.’’

Walls has left a trail of impressions through her WINGS efforts thus far.

“Maria through her actions demonstrates her passion and interest in making a difference in the lives of others,’’ Jervis said. “These qualities will carry her far in her RHS major and any additional education and career she pursues.’’

Coduti expressed similar feelings. “This experience for Maria will be very beneficial when she graduates, no matter where she is going to work,’’ she said. “Her work in developing and being president of WINGS shows skills in organization, collaboration and problem-solving – finding where there is a need and doing something about it.’’

The need is long-term in Walls’ eyes.

“I like to compare this club to building a business,’’ she said. “You start with an idea, you find people to help you and you really have to trace your steps to make sure you’re building a solid foundation that’s going to last far after I’m gone and I’ve graduated.’’

Social media awareness campaign fosters visibility and acceptance for POTS

The Pendulum, Elon University's Student News Organization
By:  Leena Dahal

Like any freshman, Maddy Gross began her school year in the fall filled with flurries of nervous, eager anticipation. The only difference was that her heart beat three times faster than everyone else ­— literally.

While her peers were adjusting to college life and preparing for classes early in the semester, Gross had to add another task to her to-do list: managing her Postural Orthostatic Tachycardia Syndrome (POTS), a diagnosis she received just three months after she started at Elon.

POTS, a disorder of the autonomic nervous system, affects the heart’s ability to circulate blood throughout the body while in an upright position.

As the syndrome causes blood to pull to the extremities, the heart rate to double or triple and the body to work twice as hard to remain in the upright position, people diagnosed with POTS often have to raise their feet to allow blood to circulate.

It was while she was in this “semi-upside down” position when Gross decided she would respond to her diagnosis in a positive and public way: a social media awareness campaign, Legs Up For POTS, that would allow POTS patients to gain visibility and support.

The journey to a diagnosis

Around the time when high school students are informed of college acceptances in March 2014, Gross, a Maryland native, began showing stroke-like symptoms, which eventually led to fainting and twitching.

After receiving every possible diagnosis — from epilepsy to brain cancer — she was prescribed seizure medicine. Still, all efforts to normalize her condition failed as her blackouts continued and her symptoms worsened.

During the summer, Gross would face a series of high fevers.

“They threw a Lyme disease diagnosis at me just based on my symptoms,” Gross noted. “The antibiotics they put me on actually made everything way worse.”

But it was at Elon where her ever-growing list of possible diagnoses would end.

Her roommate, freshman Darby Campbell, recalled the effects Gross’ symptoms had on her early start at Elon.

“She was not able to do much really because she was so sick,” she said. “She had to stay in our room most of the time, and it was really heartbreaking to see.”

After sustaining injuries from fainting in her dorm and hitting her head on a desk, Gross spent several days at Alamance Regional Medical Center and Duke Raleigh Hospital. The nurse overseeing Gross’ heart monitor at Duke Raleigh noticed that her heart would shoot up at alarming rates and shared her concerns with Gross’ parents.

After consulting a family friend who recognized the symptoms from her son’s diagnosis of POTS, Gross’ family returned to Maryland to visit a different cardiologist who officially diagnosed her with the syndrome after administering a tilt table test.

Her journey to that official declaration, which was riddled with complications and misdiagnoses, is not uncommon to many POTS patients.

The general public’s and health professionals’ lack of knowledge on POTS coupled with the variation of symptoms among patients make it one of the hardest illnesses to diagnose. 

According to Dysautonomia International, the average diagnosis period is five to six years. Alarmingly, 85 percent of POTS patients are also told at some point in their journey that it’s “all in their heads” or given psychiatric labels.

Finally under the supervision of health professionals who fully understood POTS, Gross’ mystery was solved and she could receive the appropriate medication and support she had waited for.

Living with POTS

But her story consists of more than just the diagnosis.  As POTS is a chronic illness, the medication she receives only temporarily relieves her symptoms.

The syndrome is also invisible to the outside observer, meaning Gross navigates through Elon with only a few people aware of what she experiences on a day-to-day basis.

“Even though Maddy is better, she still passes out at least once a week and has to frequently leave class to put her legs up,” Campbell said. 

According to Gross, POTS is beyond exhausting. With her heart rate spiking to unimaginable rates, she said she feels as though she is running even while standing perfectly still.

She compares the overwhelming sensations before she raises her legs to getting blood drawn.

“Can’t you sometimes feel the blood moving around? I start feeling that in my legs and feet,” she said. “It’s super weird.”

The sensations will heighten, causing her to feel more lightheaded. And then, the stroke-like symptoms occur­­ — her face becomes droopy, her words begin slurring, and she experiences difficulty speaking, moving and talking in coordination.

“It feels like my words are stuck in my feet where the blood is,” she explained. “And to connect them to my mouth takes forever.”

In these situations, if Gross does not raise her legs to circulate her blood, within a manner of minutes, she will faint — a situation she has faced multiple times during class.

“Somehow nobody notices,” she said. “I come back to consciousness really quick, but still, not fun.”

The campaign begins

During one of her visits to the gym — an activity Gross refuses to allow POTS to dictate — she decided to use the elliptical instead of the bike, even though she had been told not to exercise standing up.

“I don’t know what I expected, really,” she said. “But unsurprisingly, I started feeling my legs fill up with blood and had to go drain them.”

In a room filled with strangers, many who directed confused glances at her — clearly un- aware of what Gross was going through— this would prove to be a challenging feat.

“Not my finest moment,” she said, laughing.

With her feet in the air, her body semi-upside down, and her mind fixated on what it would be like if everyone understood — without explanation — that she was compelled to do this out of medical necessity, an idea began to flourish.

Rather than letting her idea slip when her blood finally pulled away from her extremities and the light-headedness began to fade, Gross immediately rushed home to execute it.

Envisioning a social media awareness campaign that called upon the community to post pictures of themselves with their legs up, just the way she and many other POTS patients do in order to manage their illness, Gross began “Legs Up for POTS.”

Starting with a Facebook page, her #LegsUpForPOTS campaign raises awareness about the syndrome, while encouraging others to share their own experiences  to foster an environment of acceptance, compassion and support.

 The rapid ripple effect that social media facilitates is pivotal to her campaign.

“Every person has their own social circle, so even if they’re just posting for me, they might inspire one of their acquaintances somewhere else in the world to look up POTS and try to learn something about it,” she said.

By spreading information about POTS to the general public, Gross hopes the information will result in doctors being less dismissive of patients’ symptoms and will lead to shorter diagnostic journeys.

Responses and Impact

Within a week, the page gained more than 150 likes as people from all over the country sent in pictures with #LegsUpForPOTS.

From ballet students stretching their nude flats towards the skies to a hall filled with people hanging “semi-upside down”— the immediate outpouring of support for the page was clear and powerful.

After becoming acutely aware of her community’s lack of knowledge on POTS, Maddy Gross is determined to spread information on “invisible chronic illnesses” to the general public. Photo courtesy of Maddy Gross.

According to Gross, every legs-up picture feels like solidarity in her illness. 

“It’s like saying to me, or to any POTS patient, ‘Hey, I’m trying to understand what your life is like, and you’ll never have to explain putting your legs up or whatever else you have to do to manage your illness to me,’” she said. “It tells me that they care.”

Gross’ mother, Meredith Gross, said the fact that Maddy initially felt self-conscious about putting her legs up — which often kept her from attending class or going out as much socially — inspired her to take her own legs-up photo while out in public.

“I felt a little awkward for sure,” Meredith Gross said. “But if Maddy endures some funny looks, surely I can do the same to increase awareness.”

She stressed the significance of Maddy’s campaign by highlighting that without awareness and obvious signs of disability, it is easy for the community to dismiss someone’s challenges and needs.

“The more educated [Maddy] becomes on  POTS, the more fired up she gets to solve problems she uncovers,” she said. “She has become much stronger, more patient, compassionate and self-sufficient in the face of her health challenges.”

Maddy Gross added that she hopes the campaign catches on across America and that the million people who have POTS feel less alone or weird for it because of the supportive community that the campaign creates.

“Every time I get a new picture sent in, it’s like Christmas for me.” she said. “It means so much more to me than I can explain.”

Already, her efforts have made a direct impact on lives. Multiple people have contacted Gross to ask about POTS — questioning whether they or their friend may have it.

“I hope I’ve made people feel a little less self-conscious about having to advocate for their own needs,” she said, “Even if they seem odd from an outsider’s perspective.”

Gross hopes to sustain the campaign as long as people continue sharing photos, stories and comments. She added, though, that even if nobody did, she would find another way to raise awareness — another reflection of her relentless passion and desire to make an impact on social discourse surrounding POTS.

Her self-advocacy and determination to make a universal difference while battling her own illness has inspired many of her peers.

“Maddy once told me that she wished Dr. House from the show ‘House’ was real life so that he could figure out what was wrong with her,” Campbell said. “With Maddy’s campaign, I feel like she is Dr. House for a lot of people.”

People from all across the nation have been sharing their unique #LegsUpForPOTS photos with the campaign in hopes to promote dialogue about POTS. Photo courtesy of Maddy Gross.

Community support builds

After feeling light-headed during her Global Experience class in Colonnades, Gross frantically searched for a place to raise her legs. Luckily, her classroom’s attached kitchen provided her with a space to attend to the situation, away from possible judgmental glances from her peers.

Beth Jennings, a program assistant in Colonnades, saw her lying down and approached her, asking her to move in order to avoid a situation where she would get stepped on.

Gross attempted to explain to her that she wouldn’t be able to move without fainting but Jennings insisted, concerned for her safety.

“We both wanted me to be safe, but she couldn’t understand my way of getting to that,” Gross said. “As someone who is chronically ill, I have a different view and knowledge of how I have to get to safety and health, so I knew I couldn’t move.”

Citing the incident, Campbell added that the community could improve in its support for chronic illnesses such as POTS.

“I do not think the Elon community is that accepting of POTS simply because they are not educated enough,” she said. “This situation made me really annoyed and pissed off for Maddy. When she has to put her legs up, she has to put her legs up and the Elon community needs to be more understanding and educated about her illness.”

Gross stressed that no hard feelings were directed towards Jennings or the situation. The event, to her, only represents the need to spread further awareness within the general public.

Gross said by and large, Elon, especially its professors, have been incredibly accepting of her. Whether it be on her way to class or during a Global Neighborhood House dinner in front of more than 100 people, Gross has had to “drain her legs” around large groups of people on countless occasions.

“I’ve even put my legs up on the grass right next to Inman with a friend holding my legs up for me, and no one walking to class really gave it a second look,” she added. “If people walk by and I catch them looking, I usually just give them a thumbs up so they know I’m okay.”

The university is also the first place she ever met other people with POTS. Her multiple friends and Kappa Delta sorority sisters with the same diagnosis, serve as constant motivators and sources of support.

Reaching for the skies

Though there were many moments during her first semester when she was close to withdrawing for medical reasons, Gross is determined to continue searching for more ways to help others in similar positions.

Turning every sacrifice into an opportunity, she is motivated to create a foundation at Elon to support the continuation of  her work with spreading awareness. 

She changed her major from music production, as her illness impacted her ability to sing, to undecided — hoping to find a major that would allow her to further her POTS advocacy.

“I wouldn’t want to be any place except Elon,” Gross said, “and I’ll jump through any health obstacles to stay here.”

While she is uncertain on whether she will choose POTS advocacy as her primary career path, she is sure that helping the cause is already an ingrained  passion that she plans to continue to nurture.

In the future, she hopes to also advocate for those belonging to other chronic illnesses, particularly “invisible ones” or diagnoses that are less heard of in medical discourse and whose patients feel alienated.

Gross urges the Elon community to realize that it’s harder to live with POTS than a quick Google search of it might suggest.

“Everyone’s symptoms [and experiences] are a little different,” she said. “All you can find on the Internet is stuff about how our heart rate increases too much when we change positions — which is true, and is the defining symptom — but we deal with much more than that.”

The isolation and stigma of being constantly sick can also lead to depression and anxiety among POTS patients — making a supportive network increasingly important.

Just last week, Clara Ballou, a sophomore at Elon, posted on the Facebook page, sharing her own journey towards a POTS diagnosis.

Ballou learned of POTS after hearing senior Tessa Kroninger speak about her own experience with the syndrome during ElonTHON last year.

Realizing Kroninger’s story mirrored her symptoms, she approached a doctor and after five-and-a-half-years of remaining undiagnosed, her symptoms could finally be treated.

“I never thought I would get a driver’s license, graduate high school, or attend college,” she wrote. “I know I’ll never be cured, but having people like Maddy and Tessa make this journey a lot easier.”

To Gross, these instances of community outreach and discourse represent one of the major reasons why she pursued the campaign in the first place.

“The best part has been having friends, acquaintances, and even strangers open up to me and tell me about their journey to diagnosis and where they plan to go from there,’” she said. “I support them 1,000 percent.”

She also shared that many people, combatting other chronic illnesses, have approached her with ideas for their own awareness campaigns.

“Seeing Legs Up For POTS’ direct impact is such a huge motivator for me to continue my work,” she added. “I’m so excited  for it to grow.”

With her feet often stretching toward the skies and her goals reaching even further, Gross wants those dealing with chronic illnesses to know that they are never navigating through their journeys alone.

“Don’t be afraid to do or ask for what you need to stay healthy,” she said. “Whatever that may be.”

A Balancing Act

Dysautonomia Dispatch
March 2015

There’s a reason no one says that living with a chronic illness is easy: because it isn’t. Living with Postural Orthostatic Tachycardia Syndrome (POTS), a form of dysautonomia, can be especially challenging at times. However, there are ways, with practice, to manage life with dysautonomia and find your own version of normal.

One of the most important things for me has been to realize is that no one is perfect. There will be good days, and there will be bad days. I have had bad days that felt as if they would never end. On some bad days, I get angry and upset. I want to be able to do things my peers are doing, but the fact of the matter is that I can’t always do that. I think it’s important to allow yourself small increments of time every now and again to get upset in order to release pent-up emotions. I think it’s just as important not to dwell on those bad days, though, because, in the long-run, just being frustrated doesn’t fix anything.

So, I’m not like most of my peers. This is a fact that I’ve learned to accept. In order to keep myself from spending too much time comparing myself to others, I focus on things I like and things I can do. As a college student, I spend a good amount of time on my studies, which is something pretty normal for any student, and I enjoy that sense of normalcy. Anchoring myself in school work definitely helps me. I do my best not to isolate myself from others.  I have a single dorm room, which really helps me manage my POTS since I’m able to sleep and rest when needed. While it’s sometimes tempting to stay in my room by myself constantly, I push myself to talk and interact with friends, and in the end, even if doing these things leaves me tired, I find that it also leaves me feeling better emotionally.

I would be wrong to say that I’m able to forget about my POTS entirely. Since I can’t ignore the fact that I have POTS, as that would make it far worse, I do my best to manage it. I take my medications, drink lots of fluids, increase my salt intake and exercise to keep my POTS under control (as under control as possible). With some reluctance, I use a shower chair, so I can sit down while showering, and also use a cane on days where I’m feeling especially off-balance. The reluctance is because I feel too young to need these things. I quickly realized, though, that these are tools to help me, and if there’s something that can help me, then I should take advantage of it. There is no shame in helping myself and making living with my illness easier.

Humor is something else that helps me stay positive. The reality of living with a chronic illness that few doctors know of is scary sometimes. Having a doctor say he or she doesn’t know what to do is terrifying because I thought from a young age that doctors were the people who would make me better if I was sick. There is no magic cure for me or the millions of other people living with POTS. Although I realize this, I still try to find humor in small things, like seeing ads for compression stockings online geared toward seniors and saying, “I would totally wear those,” or joking that I have a great sense of balance, when in reality sometimes I feel like I’m in a funhouse when standing on two feet, forget standing on one.

Sometimes it’s hard to do everything at once; it’s easy to get overwhelmed by school, relationships with others, and POTS. Most people my age are not so focused on their health. In the end, though, while POTS is a huge part of my life, it is not my life. I work hard to ensure that I balance everything at once so I can be as healthy and happy as possible. While I’ve yet to find the perfect balance, I’ve learned to laugh along the way.

Guest blogger Emily Deaton is a sophmore at James Madison University majoring in English and minoring in Nonprofit Studies.  She recently wrote an article on living with a chronic illness as a teenager for the Richmond Times Dispatch. When she isn’t studying, you can find her spending time with friends and participating in JMU’s InterVarsity Christian Fellowship.

Immune system disruption The search for answers

Stanford Medicine
By Kris Newby

Illustration by Jeffrey Decoster

Erin keeps a photo of herself playing soccer in the living room of her tidy cottage near San Francisco Bay. It captures her image frozen in time and space, hurtling like a comet between two opponents, her white-blond ponytail fanned out like flames.

“She was a midfielder with boundless energy, lightning fast,” recalls the coach of her Big Ten college soccer team.

Erin, in her early 30s, always assumed that soccer would be at the center of her life. As a little girl, her favorite toy was a soccer ball, a present from a cousin living in Rome. At age 4, she drew a picture of herself competing in the Olympics. In high school, she was invited to try out for the national team’s talent pool. After college, she played for the Detroit Jaguars, a semi-professional team.

But her dream of playing competitive soccer abruptly ended after a trip to Mexico in 2007.

“I was doing social work at an orphanage when I got sick,” says Erin (who asked that her real name not be used). “I passed out and was hospitalized with a high fever, low blood pressure and swollen lymph nodes. After that, I was never the same.”

Thus began her seven-year journey battling a devastating illness with no known cause or cure. She was bedridden for all but four hours a day. She could stand only for 20 minutes without fainting. But the worst symptom was the brain fog.

“It was like my thoughts were stuck in molasses,” says Erin.

No one could figure out what was wrong or how to fix it. She was labeled with chronic fatigue syndrome. Despair set in as the door to her old life slowly closed.

Interrogating the immune system

That same year a door opened on the other end of San Francisco Bay, in a windowless basement of a clinical research building at Stanford University. Here Mark Davis, PhD, an immunologist with a computer hacker’s mindset, was launching a center that aimed to break open the black box called the human immune system. This dynamic network of biological sensors, cells, secretions and genes is like a sixth sense, able to detect microbial friend from foe in the food we eat, the things we touch and the air we breathe. The most intelligent facets of the immune system are still a mystery. How does it differentiate between the cells that are part of you and the interlopers? What are the steps involved in launching an army of white blood cells to attack a microbial invader? How does the system dial down the resulting tissue-damaging inflammation? How do our traitorous cells — the cancers — make themselves invisible to our immune system?

Davis, director of Stanford’s Institute for Immunology, Transplantation and Infection, is in the right place at the right time for this quest, swimming in the primordial soup of creative disruption, Silicon Valley. At long Stanford cafeteria tables frequented by geneticists, bioengineers, math geniuses, computer programmers, surgeons and cancer biologists, ideas just happen. And sometimes, visionary entrepreneurs throw money at these ideas. Such is the case with Davis’ Human Immune Monitoring Center, which before long had enough funding to acquire a CyTOF, a time-of-flight mass spectrometer for high-speed acquisition of multiparametric single-cell data. (If someone asks you if you want one of these instruments, just say yes.)

The CyTOF enables researchers to detect 40 different components within a single cell at the rate of 1,000 cells per second. It not only measures static levels of proteins, useful in identifying different types of immune cells, but it also detects minute changes in signaling proteins within cells in response to various stimuli. Using this device, a staggering amount of data is generated. And armed with big-data analytical methods developed during the Human Genome Project, Davis’ multidisciplinary team is trying to bring order and meaning to the output.

When it’s all done, the team hopes to create a map of what a healthy person’s immune system should look like and a flow chart depicting how immune-system signaling pathways work.

The ultimate goal of Davis’ “Human Immunome Project” is to develop better tools to answer immunological questions no one can answer now. One of the first: What is wrong with the immune systems of patients like Erin, and how can we help them get better?

Mark Davis is leading a massive analysis of the immune system.

Two years into her illness, Erin was broken. On any given day, she would cycle through a laundry list of symptoms: brain fog, dizziness, light sensitivity, a sore throat, nausea, swollen lymph nodes, crushing fatigue, a racing heart, ear ringing, drenching sweats and fainting.

During this time, she had lost some of her most active and athletic friends, who grew impatient with the waxing and waning symptoms that prevented her from the leaving the house on most days.

“I had times where I’d shut the blinds, lie down and hope for a better day,” says Erin. “Literally, my escape was through my dreams. I just couldn’t stand to be in my body.”

Her life revolved around doctors’ appointments. One physician ruled out infectious diseases. Neurologists examined her for seizure disorders and brain tumors. A rheumatologist evaluated her for systemic lupus erythematosus and other inflammatory diseases. An endocrinologist agreed that the origin of her fatigue was not the thyroid, the adrenals or any other gland. A cardiologist assured her it was not her heart.

None of them could settle on a definitive diagnosis, so the physicians tagged her with the insurance code for chronic fatigue syndrome, a controversial diagnosis for a set of symptoms also sometimes labeled as CFIDS — for chronic fatigue and immune dysfunction syndrome — and ME — for myalgic encephalomyelitis. The dominant moniker today is ME/CFS.

No one knows what causes ME/CFS. Some think that an infectious agent or overactive immune system triggers it. Others blame genetic flaws, environmental factors or a combination of any of the above.

Roughly 17 million people worldwide (1 million to 4 million in the United States) have ME/CFS. It strikes people of all ages and racial, ethnic and socioeconomic groups. It is diagnosed two to four times more often in women than men.

It’s a syndrome that gets little respect in the medical community because, with no tangible cause and an ever-changing constellation of symptoms, patients often get labeled as hypochondriacs, malingerers or seekers of addictive pain medications. The primary diagnostic criterion for this condition is infuriatingly vague — “six or more consecutive months of severe fatigue” — virtually unchanged since 1994.

As Erin went from specialist to specialist, well-meaning doctors grew frustrated with their inability to help her. One day Erin blacked out while driving, almost hitting a streetlight. After another fainting accident, an emergency room physician told her, “On hot days, women faint.”

“I felt objectified, like a slab of meat,” says Erin.

Finally, in 2009 Erin was diagnosed with postural orthostatic tachycardia syndrome — which accounted for her fainting spells. For treatment, her cardiologist sent her to Stanford Hospital’s cardiology clinic to see one of the nation’s few POTS specialists, cardiac electrophysiologist Karen Friday, MD.

POTS, which often accompanies ME/CFS, is a fainting disorder associated with an abnormal increase in heart rate and low blood pressure. The mechanism is unknown, but some people develop it after contracting viral or bacterial infections like mononucleosis, pneumonia or Lyme disease. Friday prescribed fludrocortisone to manage Erin’s low blood pressure, but to explore the possibility of an underlying microbial trigger, she sent Erin to see Stanford professor of infectious diseases José Montoya, MD.

Montoya, 54, dapper in his white coat and tie and smiling widely, greeted Erin with a bear hug and told her in his thick Colombian accent, “I want to make your life beautiful again.”

“Dr. Montoya was a shining beacon of hope,” says Erin.

Montoya’s ethos to reduce patient suffering was shaped by a hardworking, single mother and the iron-fisted priests at his Catholic school in Cali, Colombia. He was accepted into medical school at age 18, after receiving the third-highest qualifying exam score in his native country that year. After medical school he went on to Tulane University School of Medicine for his residency, then joined the infectious disease division at Stanford. At Stanford he became a world-recognized authority on infections affecting heart transplant recipients and on toxoplasmosis, a common parasitic disease.

Montoya conducted a detailed medical history and physical exam on Erin, then ordered a battery of tests for viruses, bacteria and fungi. His wide-net diagnostic approach paid off; he found two blood-borne microbes — Human Herpesvirus-4 and the coxsackie virus — known to cause chronic disease and POTS.

Though Montoya wasn’t sure if these viruses were at the root of Erin’s illness or merely collateral infections, he started her on a high dose of the antiviral drug famciclovir. Erin was relieved to finally have a physician who wasn’t going to punt her case to another specialist.

“I wanted to live my life again,” says Erin.

Montoya is one of only a handful of clinician-researchers who accept ME/CFS patients, and he currently has a waiting list of about 150.

Back in 2005, while attending a conference on toxoplasmosis in Paris, Montoya told his mentor that he wanted to research ME/CFS. His mentor scoffed at the idea, pointing to a homeless person lying in a Parisian gutter.

“That’s going to be you if you go into chronic fatigue research,” the mentor told him.

The hard truth is that most medical research labs rely in large part on U.S. government funding, and the ME/CFS research budget is insufficient to support a typical university research lab.

The National Institutes of Health, the largest funder of medical research in the United States, allocated only $5 million for ME/CFS research in 2013. (To put this in context, the annual NIH research budget for multiple sclerosis, with 400,000 sufferers, is $112 million.) The reasons behind this underfunding are complicated.

One factor is that the NIH funding process favors well-defined diseases that fit neatly into medical specialties like cardiology, cancer and neurology. Most of these medical societies have organized lobbying efforts, sometimes backed by pharmaceutical or medical technology companies. Another factor is that collectively ME/CFS patients are too sick to organize, raise money and lobby for research dollars. And then there is the stigma associated with the condition; some NIH grant reviewers are reluctant to fund research because they believe that ME/CFS is a psychosomatic, “all in the head,” disorder. (To remedy this, the NIH recently created a special emphasis panel so that researchers familiar with the condition review grant applications.)

But none of this deterred Montoya, who was driven to do something for the suffering patients queuing up for appointments.

Opportunity knocked in 2008 when a wealthy donor met with Montoya to talk about the ME/CFS problem. He asked if a $5 million donation for research could make a difference.

Montoya could hardly believe the sum, replying, “Yes, give me five years.”

With the freedom of private funding, Montoya was able to take a multifaceted and rigorous approach to analyzing ME/CFS. Traditionally, NIH funding is awarded through medical specialty groups that tend to favor research that tests one narrow hypothesis about a disease. For example, a researcher might get funded to screen blood samples for one virus, or treat patients with one drug. This approach takes a long time, and researchers typically aren’t able to share and build on discoveries for years.

Montoya’s game plan was to use a big-picture, big-data strategy to find out what was wrong with patients like Erin. His first step in launching the Stanford Initiative on Infection-Associated Chronic Diseases was to convince a dozen or so academic investigators to venture out of their comfort zones to research a wildly unpopular disease using technologies yet to be developed.

Montoya convinced experts in immunology, rheumatology, genetics, bioengineering, anesthesiology, neuroradiology, cardiology, psychiatry, infectious diseases and bioinformatics to all work together. The team members would be searching blood samples for infectious microbes, inflammation-related molecules and genetic flaws. They’d do brain scans and physical exams. They’d survey study subjects for fatigue levels and medical histories. Then they’d compare all this data with that of healthy people to see what was different. Next, he launched a Bay Area recruitment campaign for 200 patients who met the Centers for Disease Control’s definition for chronic fatigue syndrome, including Erin, and 400 age- and sex-matched healthy volunteers, all of whom agreed to donate eight tubes of blood and be poked, scanned and surveyed over the next decade.

The most complex part of the ME/CFS initiative was the exploration into what was happening with the immune system of these patients. For this role, he needed an expert who didn’t care about the ME/CFS stigma or how things have been done in the past. So he called on Mark Davis.

There will be blood

Davis, in well-worn jeans and running shoes, leans back in his chair, surrounded by pillar-piles of scientific papers. At first glance one might assume that he is — in California-speak — a mellow dude.

But looks can be deceiving, because Davis, who discovered how T cells help a body fight off infections, is all about the fight. [See story, page 38.]

As if to prove this point, Davis reaches into a random stack of paper and pulls out a black-and-white photo of a collegiate fencing match.

“This is me,” he says, pointing to a man in white flying off the ground, plunging the tip of a silver foil directly between the eyes of a masked opponent. “I like to poke people.”

He then reaches into another stack of paper and pulls out the Dec. 19, 2008, issue of Immunity. It is a poke-in-the-eye to fellow immunologists, an essay titled, “A Prescription for Human Immunology.”

In this oft-quoted paper, he describes immunology as a field known for its “impenetrable jargon, byzantine complexity and acrimonious disputes.”

He also chides many of his colleagues for spending too much time on mouse studies and not enough on human studies. For immunological studies, mice are fast and easy. They can be bred with specific diseases, such as diabetes or Parkinson’s, and then dissected to evaluate the effectiveness of experimental treatments. There are relatively few regulatory, financial and ethical hurdles to working with mice. He emphasizes that lab mice live in isolated, disease-free, temperature-controlled environments, far different from the crowded, germ-ridden urban habitats of your typical Homo sapiens. (Most humans are infected with six different herpes viruses, and who knows what else.) The other problem with “mouse models” is that their common ancestors are genetically separated from Homo sapiensby some 65 million years.

Erin, a social worker and therapist, is an ME/CFS study participant. 

“Inbred mice have not, in most cases, been a reliable guide for developing treatments for human immunological diseases,” says Davis.

Instead, he would like to shift the focus of immunology research back to where it can do the most good — to humans and their blood. And along the way, he’d like to slay a few sacred cows of medicine.

First off, Davis believes it’s time to rethink the CBC or complete blood count, the most commonly ordered medical test on the planet. The CBC, which has changed little since it was put into mainstream use in the ’50s, provides physicians with relative numbers of a patient’s red, white and platelet blood cells. This test isn’t really “complete” and it doesn’t begin to capture the nuances of a working immune system.

As researchers gain a better understanding of this system, he’d like to develop a new set of metrics for immune system health that communicates more of a continuum of health rather than a black-and-white declaration. If the immune system is underactive, a person is open to infections, mutations and premature aging. If it is overactive, a person may suffer from allergies, autoimmune disease and excessive inflammation. Davis wants to redefine health as an immune system in balance, then develop better reporting tools to help clinicians determine if a patient is fighting a virus, a bacteria, an allergy or environmental toxins.

Davis’ field of dreams for this effort is Stanford’s Human Immune Monitoring Center. Launched in 2007, today the center consists of dozens of instruments that provide standardized, state-of-the-art immune system analysis at the RNA, protein and cellular levels. Its gene-sequencing instrumentation is located in a nearby building and shared with the Stanford Functional Genomics Facility. For researchers both inside and outside of the university, the center’s 15-person staff provides a one-stop shop for these services. At the start of a project, the center’s director, Holden Maecker, PhD, meets with investigators to help plan studies and determine needs, such as what samples to take, how to store those samples and which tests will best answer their scientific questions. There is also assistance on results archiving, reporting and data mining.

“We have about 60 different projects under way at the center right now,” says Maecker. These include searches for immune biomarkers for aging, Alzheimer’s, autoimmune disease, cancer, chronic pain, rejection in organ transplantation and viral infections.

“I believe this is the only facility of its kind anywhere,” says Davis.

Montoya’s chronic illness initiative is the largest project in the HIMC at this time, and the complexity of the task ahead is daunting. The staff is looking for meaningful patterns in the many components of the 600 blood samples, including dozens of cytokines, 35 cell-surface proteins, 15 or so types of blood cells, and more than 47,000 genes and regulatory nucleic acids. The challenge is not only to quantify the normal ranges for these components, but also to understand relationships between the components and reverse-engineer the cascade of biochemical reactions that drive immune system processes. He anticipates it will take about a year to run all 600 samples through the processes.

“It’s like dumping a hundred different puzzles on the floor and trying to find two pieces that fit,” says Davis.

The workhorses for these tasks are the center’s two CyTOFs. Stanford has seven of these $630,000 instruments, more than any other academic medical center, thanks to Garry Nolan, PhD, a Stanford professor of microbiology and immunology. Nolan purchased the first commercially available CyTOF, and as an early adopter developed protocols for using it in cancer biology, immunology and cell biology. He now holds equity in Fluidigm, a company that manufactures the machines.

Infectious disease expert José Montoya is looking for causes of chronic fatigue.

His enthusiasm for the technology and his willingness to share what he’s learned has catalyzed an active Stanford community of CyTOF experts.

“With seven CyTOFs on campus, Stanford continues to innovate and lead the way in ‘deep-profiling’ studies of the immune system,” says Nolan

Through this work, the Stanford team hopes to gain a better understanding of the complex, inner workings of the immune system. This will ultimately give physicians and their patients the tools to answer the fundamental question, “How is my immune system doing today?”

Putting the pieces together

This past March, four years after the launch of the ME/CFS initiative, Montoya held an all-day symposium to present early findings on what’s happening within the hearts, blood, brains and genomes of ME/CFS patients. The lecture hall was packed with researchers from Australia, Canada, the United Kingdom and the United States, as well as patients, all eager for any news on a research agenda that had been stalled for decades.

At the end of the day, the biggest news was the identification of a number of biological markers that indicate ME/CFS patients may be suffering from out-of-control inflammation.

First up was a neuroinflammation researcher, Jarred Younger, PhD, who worked with the HIMC to measure daily fluctuations of 74 blood markers and cytokines. For this study, published in the Journal of Translational Medicine (http://www.translational-medicine.com/content/11/1/93), volunteers gave blood once a day for 25 days, and reported their fatigue levels on a hand-held computer twice a day. (Younger moved to the University of Alabama in Birmingham in August.) Through complex statistical analysis, the team found 12 cytokines that were consistently elevated on days that ME/CFS patients felt the most fatigued. One of these cytokines, leptin, activates microglial cells, the brain’s first line of defense against infections. When microglial cells are primed, they start pumping out signaling chemicals that generate the flulike symptoms commonly reported by ME/CFS patients — fatigue, headaches and brain fog.

Amit Kaushal, a medical resident with a PhD in bioinformatics, did the first pass on genomic analysis. For his part of the investigation, he scanned the blood of 200 ME/CFS patients and 400 healthy subjects for 47,000 gene elements, then ran this data through the Nextbio Disease Atlas, a publically accessible database that catalogs gene markers associated with specific diseases. After analysis, he found genetic markers in the blood of ME/CFS patients similar to those in patients with well-defined chronic inflammatory diseases.

The quarterback for the search for infectious microbes is W. Ian Lipkin, MD, a renowned microbe hunter and the director of the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health. He is using high-throughput sequencing platforms that enable rapid identification and molecular characterization of known and novel disease agents.

“We decided to go in without any preconceived notions about what we’d find,” says Lipkin. “Our approach is comprehensive, rigorous and quite deep.”

In the first analysis, his team found no significant differences in the types of infectious organisms present in the blood of people with ME/CFS or their matched normal controls. In the next phase he’ll search inside the blood cells and analyze the gastrointestinal microbiome for the presence of bacteria or viruses that may trigger the immunological disturbances that are so disabling in ME/CFS. The objective of this work is to identify the agents responsible for initiating and perpetuating disease. This could lead to vaccines, drugs or probiotic interventions.

While not all of these results have been published or independently confirmed, the researchers were excited about finding measurable, physical differences between ME/CFS patients and healthy controls. (Stanford assistant professor of radiology Michael Zeineh, MD, has identified structural brain abnormalities in the ME/CFS patients — findings are slated for publication in the coming months.) More pieces of the puzzle are coming together, providing other ME/CFS researchers with ideas to build on. For ME/CFS patients it was validation — their symptoms are real, with measurable biological markers.

Eight months after seeing Montoya, Erin’s recovery from ME/CFS started with fleeting windows of cognitive clarity. She was on high-dose antivirals and POTS medications for about five years, and her recovery was infuriatingly slow and inconsistent. It was like wiping off a mirror in a steamy bathroom. She saw her former self briefly, then the image fogged over again.

Montoya doesn’t know why these drugs worked for Erin, but he knew from treating other patients that beating back viral infections sometimes helps get an immune system back into balance.

Erin also believes that the antiviral and POTS drugs were instrumental in her recovery, but other factors — family support, meditation and Montoya’s coaching — were also important.

One of Montoya’s key messages to ME/CFS patients is this: If you have one good day, don’t try to make up for lost time by overexerting yourself.

“Don’t burn out your engine,” says Montoya, because the resulting crash can reset the recovery process by months.

And at appointments he would remind Erin, “Take in all the love that is all around you and use it to heal.”

During her illness, Erin’s mother became her advocate, managing her medical issues and driving her to appointments. Her father added her to his health insurance policy so she could afford the visits to medical specialists. And her sister, who is her best friend and housemate, was her wingman.

“My sister was my voice of hope,” says Erin. “She’d tell me, ‘OK, you took five steps forward and two back today, but maybe tomorrow you’ll take six steps forward and only one back.’”

It’s been seven years since Erin fell into the abyss of a mysterious illness. This girl interrupted, now a woman, is picking up the pieces of her life and starting to live again.

Today, she works as a social worker and therapist. She plays soccer in a local league. She’s also started dating again. It gives her hope that researchers are finally focused on ME/CFS and that others may be able to benefit from the treatment that has given her life back.

As she packs for a camping trip, she reflects on how this illness has changed her.

“It’s made me a person of more depth and compassion,” says Erin. “Before, I’d been so active, I didn’t have the opportunity to sit with myself in this way and take a deeper inward journey. Adventure had been the focus of my life. As I sit with clients who are coming in with devastating situations, with unknown futures, I’m able to share with them hope and the power of self-fulfilling prophesies. I help them find those things inside, spiritually, that will help them meet the adversities in their lives.”

At this point her voice becomes soft, almost a whisper, as she says, “I’ll always miss playing soccer at a competitive level, but I’ve gained so much. It’s helped me reinterpret what success looks like. It’s not everything you achieve and how many games you win. It’s the process of getting there. This is my biggest achievement — recovering from this illness.”

In soccer, a “hat trick” is where a player scores three goals in a row. Montoya achieved his first goal, the launch of the first major ME/CFS research initiative, with a little funding luck and the recruitment of a top-notch research team. With the assistance of Davis and his immune system hackers, he’s close to reaching his second goal: the identification of biomarkers and causes, which will enable physicians to provide a definitive diagnosis and treatment options to patients suffering from this debilitating condition.

The third goal of his hoped-for hat trick will be a whole new way to look at the human immune system. It’s a game changer. It will provide researchers with a new playbook of research strategies to help them discover the causes of other confounding conditions, from Lyme disease to multiple sclerosis to fibromyalgia. It will provide clinicians with a better set of metrics for assessing patients’ health. And then the patients lying in dark rooms with forgotten diseases, whose numbers could fill hundreds of soccer stadiums, will have reasons to stand up and cheer.

Brain attack An explanation for a mental illness that strikes out of the blue

Stanford Medicine
By Erin Digitale
Illustration by Jeffrey Decoster

On March 2, 2009, something snapped inside Paul Michael Nelson. In the middle of the night, his parents found the 7-year-old boy stabbing the door of the family’s home office with a kitchen knife, trying to get at a computer that was off-limits after his bedtime. When they stopped him, he flopped around the floor on his knees, barking like a dog. He tore at blankets with his teeth and spoke in gibberish.

It was Paul Michael’s first episode of psychosis.

“It was like he was demon-possessed,” says Mary Nelson, his mother.

The Nelsons rushed to their local emergency room, where staff didn’t seem to believe their account of the intensity of the outburst and said it must have been just a temper tantrum. The staff wrote a referral to a psychiatrist and sent him home. The next day, the Nelsons took Paul Michael to the psychiatrist. She was about to give him an antipsychotic, but changed her mind after reading his blood work.

“She said, ‘Oh, my God, he’s got low platelets; I can’t prescribe this,’ and she shuffled us out,” says Paul Nelson, the boy’s father. Paul Michael’s levels of platelets, the blood cells that form clots to stop bleeding, were far below normal, but the Nelsons were not sure why the psychiatrist thought this justified avoiding antipsychotics. After the family left the psychiatrist’s office, Paul saw his son, who seemed to have held himself together for the doctor, becoming overwhelmed. “He’s very scared; he knows something’s wrong. When she shut the door, it felt like the doctor shut us off.” When the family got home that day, Paul Michael exploded into another psychotic fury.

Sucked into the whirlpool of Paul Michael’s compulsions, rages and delusions, neither the Nelsons nor the doctors who took on Paul Michael’s case realized that the little boy’s abnormal blood work held an important clue to what was wrong. It took months and several psychiatric hospitalizations before anyone recognized that Paul Michael’s case illustrated an alarming phenomenon: Your immune system can make you crazy.

When the immune system gets derailed from its usual infection-fighting role and attacks the brain, it can trigger obsessive-compulsive actions, anorexia-like refusal to eat, severe anxiety, violent outbursts and other symptoms of mental illness, as well as a host of neurological problems — in the worst cases, seizures, respiratory failure and death. Although doctors recognize a handful of immune-mediated neurologic diseases in children and adults, their awareness of the immune connection to mental illness is limited.

That’s slowly changing. Instead of hot-potatoing such puzzling cases out of their offices, as the Nelsons’ first psychiatrist did, some physicians are working to understand the mechanisms and develop treatments for autoimmune diseases that attack not just the brain but also the patient’s personality, the intangible spark we call the self.

It’s not easy. There’s no diagnostic lab test for pediatric acute-onset neuropsychiatric syndrome, or PANS — the name for this list of devastating symptoms — and the list probably encompasses an array of similar but not identical brain diseases, most of which still have unknown causes. But in spite of the stumbling blocks and the scientific disputes they’ve engendered, answers are emerging, in large part because of a Stanford team’s efforts to conduct research and treat affected children in the country’s first clinic to address the disease.

A family’s agony

Paul Michael’s second breakdown happened after his family returned home from that unsuccessful psychiatrist visit, March 3. It was so violent that his parents called the police. He was doing some of the same alarming things as the night before — flopping around, speaking in gibberish — but was also tearing up his room, causing his parents to worry that he might find an object there that he could use to hurt himself. Paul tried holding the little boy to calm him, but Paul Michael fought his dad with what seemed like superhuman strength. The police took him to the hospital on a 5150, California’s code for involuntary restraint of persons who are a danger to themselves or others. He was in and out of a pediatric psychiatric hospital for several months.

Meanwhile Paul and Mary began their search for answers, starting with Paul Michael’s general pediatrician and the psychiatrists, social workers and counselors they found through their health insurance provider and the psychiatric hospital where Paul Michael stayed. Most of these caregivers ascribed Paul Michael’s problems to a family history of psychiatric illness (both parents had depression and bipolar disorder in their extended families), poor parenting or outright child abuse.

The Nelsons were willing to try anything to become better parents. “If I’m doing something wrong, I want to know,” Mary says, adding that “We felt like, we’ve somehow got to try to survive because we love him so much.” But they were grieved and confused, too: “We met with counselors at the psychiatric hospital who were saying things like, ‘Mom, you’re too codependent’ — and I might be, but I knew I didn’t cause my kid to go psychotic.”

Paul ticks off the strategies they tried, following counselors’ suggestions, to improve their family environment: rewards for good behavior, lists of skills to utilize, contracts, daily affirmations … until both parents chuckle ruefully at the futility of those efforts in the face of Paul Michael’s uncontrollable compulsions and rages.

Although the suggestion that they were abusing their son pained them, they knew why it crossed people’s minds: He was always covered in bruises. More than once, the police showed up to a scene of one parent restraining an explosive Paul Michael, and, to an outside observer, it was hard to tell what was really going on. Paul had been a San Francisco sheriff’s deputy for 27 years before retiring to return to school, so he could easily see these scenes from the officers’ perspective. There were times he found himself consoling the officers because they had never seen a young child so distressed.

At first, the only dissenting medical expert’s voice about the origins of Paul Michael’s illness came from Mary’s colleague William Benitz, MD, a professor of pediatrics at the Stanford School of Medicine, where Mary was a human resources manager in the neonatology division. Benitz urged the Nelsons to take Paul Michael to a rheumatologist who could investigate whether an autoimmune disease could be causing both their son’s very low platelet count — which could explain his constant bruising — and his sudden psychiatric symptoms.

“I have a rule of thumb for pediatric patients: They’re only allowed to have one disease at a time,” Benitz says. “It’s not 100 percent true, but for a previously healthy 7-year-old to develop what appeared to be psychiatric and hematologic symptoms from two different, independent processes didn’t make sense. There had to be a unifying diagnosis.”

Then, the Nelsons ended up at Stanford Hospital’s emergency department during one of Paul Michael’s outbursts, where they sawRichard Shaw, MD, a professor of psychiatry and behavioral sciences and a child and adolescent psychiatrist at Lucile Packard Children’s Hospital Stanford. Observing Paul Michael’s behavior, Shaw told the Nelsons that they weren’t dealing with schizophrenia or bipolar disorder; instead, he suspected vasculitis or brain inflammation. His opinion spurred the family to keep searching for a diagnosis.

Paul saw his son, who seemed to have held himself together for the doctor, becoming overwhelmed. “He’s very scared; he knows something’s wrong." 

A history of controversy

When Paul Michael became sick in 2009, the concept of autoimmune psychiatric disease was barely on doctors’ radar. It wasn’t until September 2012 that Lucile Packard Children’s Hospital Stanford opened the country’s first clinic devoted to treating children with PANS, which is still the only clinic to couple the expertise of psychiatry and immunology/rheumatology for these patients.

Children who meet diagnostic criteria for PANS have sudden, severe obsessive-compulsive behavior or anorexia, along with so many other problems that the child can barely function. These may include separation anxiety so powerful the child cannot bear to be more than a few feet from a parent, bizarre inhibitions about food, deterioration in schoolwork, intense insomnia or, as the Nelsons observed in Paul Michael, violent rages when the child’s obsessions cannot be satisfied.

“In some ways, it’s like having your kid suddenly become an Alzheimer’s patient, or like having your child revert back to being a toddler,” says Jennifer Frankovich, MD, clinical assistant professor of pediatric rheumatology at the School of Medicine and one of the clinic’s founders. 

“We can’t say how many kids with psychiatric symptoms have an underlying immune or inflammatory component to their disorder, but given the burgeoning research indicating that inflammation drives mood disorders and other psychiatric problems, it’s likely to be a large subset of children and even adults diagnosed with psychiatric illnesses,” says Kiki Chang, MD, professor of psychiatry and behavioral sciences.

Chang, a pediatric bipolar expert, was drawn to collaborate with Frankovich in founding Stanford’s clinic because many PANS patients are first suspected of having bipolar disorder. But although their symptoms begin as abruptly as bipolar manias, they are not manic. Talking about these mystifying children (among them Paul Michael, whom the doctors now consider their first PANS case), Chang and Frankovich realized the only thing that was clear was that the children and their families desperately needed help. Nearly everything else about PANS was up for debate. “A lot of academic physicians have said ‘This does not exist; it’s just bad behavior, and there are a lot of reasons for kids to have bad behavior,’” Frankovich says.

For many years, controversy dogged PANDAS, the provisional diagnosis that preceded PANS in the medical literature. The phenomenon, which was first reported in the 1980s by Susan Swedo, MD, now a senior investigator at the National Institute of Mental Health, included sudden emergence of OCD or tics (repetitive, hard-to-control vocal or physical movements) in the wake of strep infection. Swedo’s theory was that the body’s response to infection went awry and triggered an autoimmune attack on the brain. She succeeded in treating some cases with either long courses of antibiotics to kill strep bacteria or, if that didn’t work, various immune therapies.

However, many healthy children carry strep bacteria, one of several factors about the biology of strep that have made it difficult to clarify the bacterium’s role in the disease. So the syndrome’s critics have contended that the kids simply had run-of-the-mill Tourette’s or obsessive-compulsive disorder plus, perhaps, some behavioral problems caused by bad parenting.

The treatments Swedo proposed have risks. One of them, long-term antibiotic therapy, can favor development of antibiotic-resistant organisms. Another, treatment with immunosuppressants, puts kids at risk for serious infections. But the children’s symptoms were extremely debilitating, and the treatments seemed to help. Swedo was frustrated that, in her view, the science was being stalled by critics’ dismissal of the immune-system connection.

Frankovich and Chang acknowledge the dearth of science to explain most cases of PANS, but say that’s why Stanford’s clinic is so important: It provides a critical mass of patients for answering scientific questions. Other institutions, such as Harvard-affiliated Massachusetts General Hospital and the University of South Florida in Tampa, have joined Stanford in committing resources to study and treat the disease, and more programs are under development.

“Maybe we’ll go back and say, ‘We were wrong; it’s all parenting,’” Frankovich says, sounding simultaneously tongue-in-cheek and strained. “But we have to try.”

A discovery that changed minds

The 2007 discovery of a molecular explanation for some cases of autoimmune encephalitis — a specific form of brain inflammation caused by an immune attack — has made a big difference in convincing physicians to look for autoimmune underpinnings when patients suddenly seem to go off the deep end.

In this disease, known as anti-NMDA receptor encephalitis, an antibody made by the patient’s immune system attacks a receptor for a single neurotransmitter, N-methyl-D-aspartate, producing psychiatric and neurologic disturbances. For instance, a patient may first show anxiety, paranoia and hallucinations, progressing to movement disorders and seizures. In the worst cases, patients develop irregular heartbeat and breathing, go into a coma and die. But quick diagnosis and treatment can reverse all of this. The book Brain on FireSusannah Cahalan’s 2012 best-seller describing her bout with the disease, raised awareness. Though at the height of her illness, Cahalan was severely debilitated with paranoia, hallucinations, seizures and cognitive impairment, she received treatment, made a full recovery, returned to her job as a New York Post reporter and became an advocate for other autoimmune encephalitis patients. 

Quelling the symptoms

Finding a specific antibody that triggers PANS symptoms would make treatment much easier. But most patients have no known biomarker of their illness. In this, though, Paul Michael was lucky. At the beginning of the summer of 2009, a physician in the Nelsons’ insurance network referred him, at Benitz’s suggestion, to Frankovich. (The insurer didn’t have an in-network pediatric rheumatologist within 50 miles of the family’s Half Moon Bay, Calif., home, so he was able to go outside the network to see her.) From blood tests, Frankovich discovered that Paul Michael had elevated anti-B2G1 antibodies. These antibodies bind a specific component of cell membranes and target platelets for destruction; they are also associated with blood vessel disease that can cause neurological symptoms such as chorea, a movement disorder that can co-exist with behavior disorders. Paul Michael also had some blood markers of lupus, an autoimmune disease that can attack the brain, though he didn’t meet full diagnostic criteria for that disease.

At first, Frankovich had no evidence to prove that the anti-B2G1 antibody or lupus markers were contributing to his psychiatric symptoms, but in a sense that didn’t matter. She was a rheumatologist, and she had found an immune abnormality — autoimmune platelet disease — that clearly needed treatment.

In early June 2009, Frankovich began giving Paul Michael powerful immune-suppressing drugs. His platelet count rose and his psychiatric symptoms eased. After having spent 61 days in emergency rooms and psych hospitals between March and May, Paul Michael spent nearly all of June and July at home, visiting the emergency room only three times. Paul and Mary began to hope that things were turning around.

But then, in December 2009, Paul Michael got the flu and Frankovich stopped his immune-suppressing medications so he could recover. His body fought off the virus, but his platelets dropped and his rages surged back.

“He had a five- to six-month flare,” Mary says. “It was heartbreaking.”

“We had to start over,” Frankovich says. The second time she tried suppressing Paul Michael’s immune system, he didn’t respond to one of the medications she had used initially, so she switched to a stronger drug. In the subsequent months, Frankovich shifted the medication doses up and down to investigate whether Paul Michael’s autoimmune disease was connected to his psychiatric symptoms. His regression when he had the flu, she concluded, was not a fluke: When Paul Michael’s immune system was not being suppressed, his platelets fell and his rages became more frequent and intense. She became increasingly convinced an autoimmune process was causing both his low platelets and his psychiatric symptoms.

But she had trouble getting others to agree that there was a connection. “Even though our psychiatrist at Stanford believed the two problems were related, the non-Stanford psychiatrists the family was seeing through their insurance provider didn’t understand what was going on medically,” she says. “They were looking at this as a kid with a behavior disorder, saying it must be a parenting issue.”

By June 2010, police had responded to 5150 calls from the family 17 times. Exhausted by trying to care for him, his parents felt they had no choice but to have Paul Michael live at a psychiatric institution.

For 15 months, Paul Michael became a residential patient at Edgewood Center for Children and Families, a San Francisco facility that provides the highest level of psychiatric care available below a locked psychiatric unit. Edgewood had a much more structured, predictable environment than any family could reasonably provide at home, and unlike parents who had to be “on” 24 hours a day, the caregivers worked in shifts. Even there, though, Paul Michael’s rages occasionally escalated to the point that the police were called. Paul and Mary visited several times a week, while also trying to return a sense of normalcy to the life of Paul Michael’s older sister, Amanda.

Meanwhile, Frankovich struggled for months to convince even the Nelsons of the connection between their son’s immune and psychiatric problems. “They were so disabled by his psychiatric disease that it was hard for them to have insight into what was going on,” she says.

For a long time, Paul and Mary dissected their own behaviors to try to figure out how they might have sparked episodes of Paul Michael’s rage.

“We were looking for triggers, but there was no trigger,” Paul says. When the illness was at its worst, it was impossible to avoid setting the boy off. “If it wasn’t going to happen at 9 when the phone rang, it would be at 9:15 when the cat wanted to go out,” Paul says. The Nelsons eventually discarded the concept of triggers. “Now, when he’s getting edgy, we call it ‘storm season,’” Mary says.

“This illness has leveled our pride and our expectations,” Paul says.

“There has been a lot of grief for both of us, his sister and for him, too,” says Mary.

“But it’s lucky he had the clear autoimmune blood disorder, because it allowed us to use immune-modulation therapy,” says Frankovich. “Had he just come in with behavioral deterioration, he would still be in a mental hospital.

Hunting for answers — and treatments

Because it’s unclear whether PANS is actually one disease or many, Frankovich and Chang are conducting research to clarify the jumbled picture presented by all 70 children they’ve seen to date at Stanford’s PANS clinic. In one study, they’re looking for genetic markers that appear more often in PANS patients, the first step toward figuring out whether certain genes increase a child’s vulnerability to the disease.

They’re also using brain imaging to ask how PANS could change two brain regions. One of these, the basal ganglia, plays important roles in fine-motor control and in fine-tuning mood and anxiety. It is also a region where the blood-brain barrier tends to break down, providing a possible entry for antibodies, which researchers suspect may attack the brain.

Figuring out whether PANS patients make antibodies against their own brains is perhaps the most important key to the disease’s mysteries. The research bears similarities to the discovery of anti-NMDA receptor encephalitis, and the path to that breakthrough may provide a road map of sorts for PANS researchers.

“You first need a critical mass of patients, but it doesn’t need to be very big,” says Josep Dalmau, MD, PhD, who led the anti-NMDA discovery. The professor of neurology at both the University of Pennsylvania and the University of Barcelona notes that his team’s first report of anti-NMDA receptor encephalitis included just four patients with very similar conditions. “In my experience you need clinics, and a good group of clinicians who can see all these patients and group them in some way.”

After grouping them, Dalmau’s team searched the patients’ cerebrospinal fluid for unusual biomarkers, finding an out-of-place antibody common to all four patients. The clincher was that this antibody attacked the brain.

“It’s very clear-cut: You see the antibody beautifully reacting with neurons, and see that the antibody binds to the brain and decreases the number of NMDA receptors,” Dalmau says. “There’s no ambiguity. We don’t see the antibodies in patients without the disease.”

There are hints that PANS may also be associated with misplaced antibodies. Madeleine Cunningham, PhD, professor of microbiology and immunology at the Oklahoma University Health Sciences Center, has developed a possible PANS diagnostic panel that tests for one brain enzyme and four antibodies against different brain proteins.

“The evidence she has published is strong, but it’s just the tip of the iceberg,” Frankovich says. “We still have a lot more work to understand what these four antibodies mean and how reliable they are in the clinical setting.” For one thing, healthy people have low levels of these antibodies; scientists still don’t understand what constitutes a critical level of these antibodies and why they enter the brain. Clinical studies at several sites around the world are attempting to independently validate the panel.

Frankovich is not disheartened by the gradual nature of Paul Michael’s improvement. It takes time for the bombarded brain to recover from immune attack, she points out.

Circumstantial evidence also suggests antibodies contribute to PANS, Cunningham notes, because plasmapheresis, a technique in which a patient’s plasma is replaced with the plasma of a healthy individual, has successfully treated some PANS patients.

“Plasmapheresis removes antibodies and the person gets better,” Cunningham says.

An immune-suppressing treatment, intravenous immunoglobulin, or IVIG, may also help. IVIG, a blood product consisting of IgG antibodies from healthy donors, is infused into the patient to tamp down inflammation. Scientists aren’t entirely sure how it works, but the NIH’s Swedo is now conducting a phase-3 clinical trial of IVIG versus placebo to see if it’s an effective PANS treatment, part of her larger effort to standardize PANS therapy.

And the larger scientific community is talking more about PANS and PANDAs, too. For example, the Journal of Child and Adolescent Psychopharmacology is publishing an October 2014 special issue on the diagnoses.

Without a universally accepted PANS treatment, Stanford’s doctors currently approach PANS patients one symptom at a time. Depending on the patient’s presentation and what the clinical workup reveals, treatments possibly employed include immune-modulating drugs if autoimmune markers or signs of inflammatory disease are present, or antibiotics for repeated sinus or throat infections. They occasionally use limited trials of high-dose steroids to help suss out whether inflammation is behind the symptoms, an approach that’s also used for some forms of encephalitis. Chang often addresses psychiatric symptoms with lithium, which has a long history as a therapy for bipolar disorder, but may be generally protective for the brain. “We’re trying to support these children’s brains and lives as best we can,” he says.

A family looks forward

Today, Paul Michael is almost 13 and his condition is much better; Mary estimates he is “90 percent back.” After 15 months living at Edgewood, he moved home and spent another two years mostly as a day patient at the facility, with some shorter hospital stays when things temporarily became worse. He transitioned in the fall of 2013 to a special-needs classroom in a public school near his family’s home. He attends mainstream classes for three subjects, something the Nelsons could never have imagined during the worst days of his illness. Frankovich’s attempts at weaning his immunosuppression resulted in simultaneous flares of his blood disorder and his psychiatric symptoms, so he is now on a longer term protocol similar to that used to treat diseases like lupus. And it’s been more than a year since his last serious outburst of rage.

In other diseases where the immune system can hurt the brain, such as lupus, controlling the autoimmune attack takes up to five years. So Frankovich is not disheartened by the gradual nature of Paul Michael’s improvement. It also takes time for the bombarded brain to recover from immune attack, she points out. “It’s the same as in brain trauma; even after we get the inflammatory response under control, it still takes time for the brain to heal,” Frankovich says, adding that she thinks it is likely that Paul Michael will ultimately be able to complete school, hold a job and live independently.

Paul and Mary are grateful for how far their son has come.  “Now that he’s doing really well in school, and has been mainstreamed in three classes, that gives me hope,” Mary says. “I’m cautiously optimistic.” Paul Michael loves to make art and has excellent visual-spatial reasoning skills. In her office, Mary proudly displays several examples of this ability, among them a perfectly proportioned, 2-inch, orange-and-white guinea pig crafted out of looped-together rubber bands. Paul Michael planned and made the three-dimensional critter on a rainbow loom, a tool most kids use for much simpler projects, such as making bracelets. The family has begun talking with him about careers that might put his spatial ability to use, such as engineering or art.

Of late, they’ve been granting Paul Michael more independence as well. “He walked to the store alone yesterday,” Paul says during a conversation in July 2014. “That’s freedom a teenager needs, he can do it, and he’s happy with himself. It’s a real good development.”

But Paul and Mary never feel like they can let their guard down, either. The disease could recur. The immune-suppressing medications Paul Michael takes have potentially serious side effects, including increased risk for infectious diseases and some cancers. And they worry about what happens if he stops the medications.

“He can be extremely volatile,” Mary says. “But when he’s not, he’s this perfectly wonderful, creative, artistic, loving guy.”

Seeing the struggles that patients like Paul Michael endure has convinced Frankovich she’ll be treating PANS patients for a long time, in spite of all the obstacles.

“Some days, I think ‘Why are we doing this? It’s so frustrating and hard,’” she says. “Other days, I see a kid we clearly made better. I’ve seen families crying, saying, ‘I haven’t had my kid in a year, and now I have my kid back.’ We cannot give up on this. There are so many of these cases out there.” 

Erin Digitale is the pediatrics science writer for the medical school’s Office of Communication & Public Affairs. Email her at digitale@stanford.edu.

Hollywood has it wrong: I’m a teenager with an illness, and it’s not glamorous at all

The Washington Post
By Lillie Lainoff September 12

Lillie Lainoff is a sophomore at Yale University.

In 2008, it was all about vampires. In 2011, it was dystopian societies with corrupt governments. And now, 2014 seems to be the year of teenagers with fatal diseases.

As far as Hollywood obsessions go, the first two are pretty benign. In real life, there are no supernatural creatures roaming the streets at night thirsting for human blood, no game shows forcing adolescents to fight to the death. Romanticizing those subjects isn’t that worrisome. A vampire is never going to write “Twilight” author Stephenie Meyer to tell her: “I’m not being portrayed properly, and now everyone thinks I sparkle.”

But teenagers with illnesses do exist. I am one of them, and it hurts to see movies and television glamorize our suffering.

When I was 14, I was diagnosed with an autonomic nervous system disorder called postural orthostatic tachycardia syndrome (POTS) that causes extreme dizziness, fatigue and other debilitating symptoms. At first I was just more tired than usual. But then, as I entered high school, I found myself unable to complete even the simplest tasks. I went from being a nationally ranked sabre fencer to having to crawl to the shower in the morning, my body too weak to stand up.

My mom would wake me up at 7 each morning to lift my legs in the air so the blood that had pooled in my feet, a side effect of the disorder, could more easily make its way back to my heart. Instead of spending my time between classes talking to friends, I hid in the bathroom to take blood-pressure medication, upwards of 20 pills a day. As time went on, I spent less time at school and more at home, in my bed, too exhausted to move.

In the past five years I’ve spent quite a bit of time in emergency rooms and hospitals across the country, and none of the patients I’ve seen were anything like the characters in the hospital portrayed in the pilot episode of “Red Band Society,” a new Fox show premiering Wednesday.

Viewers glimpse the lives of teenagers living in a fictional pediatric ward, including: Leo and Jordi, who are both suffering from bone cancer; Dash, who has cystic fibrosis; Kara, who has an enlarged heart; Emma, who has anorexia; and Charlie, who’s in a coma that is not explained. Most of the characters seem plucked from any high school and placed into a hospital. Their medical conditions are a side note; they look bright, well-rested, everything that patients in hospitals are not. The one exception is a character who is bald because of chemo.

I’ve been to the Mayo Clinic in Rochester, Minn., and Children’s Hospital in Washington. Unlike Dash, who runs around pulling hijinks, the boy I saw with cystic fibrosis was resting on a couch next to his mother, his face tinged a purplish blue. The teenagers going through chemotherapy weren’t racing down the hospital hallways in wheelchairs; they were holding onto plastic buckets in case they threw up. I’m not saying they were never happy. I can still remember the smile of a 6-year-old girl whom I sat next to in a waiting room at Mayo, glimpses of her balding head showing through a floral-printed scarf. While most children her age seem to have boundless energy, she sat quietly. At least half of the patients were attached to heart monitors or oxygen tanks, or were in wheelchairs.

“Red Band Society” is being lauded as a departure from the idealization of teen chronic illness and death in recent young-adult books and movies such as “The Fault in Our Stars” and “If I Stay.” Merrill Barr writes in Forbes that “what audiences will immediately take notice of in Red Band Society is its willingness to not sugarcoat the reality of the patients’ various situations.” But based on the pilot, nothing in how the patients are portrayed is realistic. The viewer never sees a character taking medication, going through a treatment or doing anything that a typical patient does in a hospital.

Compared with “The Fault in Our Stars” and “If I Stay,” in many ways “Red Band Society” (I watched the pilot during a free Web promotion) is more damaging and hurtful because it seems to assume that most sick teenagers can do everything healthy teenagers do — from having enough energy to go to parties to being optimistic about their situations.

Maybe I’d feel differently about the show if the ever-talented Octavia Spencer had been my nurse and had bought me 10 boxes of pizza, like she did for one of the characters in the pilot. I had excellent nurses, but it was clear that they were there to provide medical care, not to be my friends. Maybe if my hospital rooms had had huge windows and freshly pressed, colorful sheets and blankets, and had been large enough to fit 20 people comfortably, I would have been less miserable. But I doubt it. In “Red Band Society,” these props mask the gravity of the kids’ illnesses. But no matter how many cool posters or flat-screen TVs the set designer puts on the walls, they are still the walls of a hospital room.

In some ways the show’s faux-realism could be considered positive. I understand the power of portraying sick teenagers as “normal.” No one should be defined by his or her illness. However, I would be lying if I said that my disorder did not shape who I am. Although my condition is under control, it is something that is always present, that I will have to struggle with. Yes, I am more resilient and thankful for the life I have. But I would give up that gratitude if it meant that I could have never been sick, because, along with newfound strength there is emotional exhaustion. Aside from feeling horrible physically, I became more guarded, unwilling to let even my closest friends know how I was coping. And there is the constant fear that my disorder will get worse again, that I will lose everything I have worked for.

One of the best pieces of advice from my doctor at Mayo was: “Do not wear the bracelet,” meaning that I shouldn’t let my illness become my identity.

I am not my illness. But it is part of me.

According to “Red Band Society’s” Leo, “Your body isn’t you, your soul is you, and they can never cut into your soul.” However, the show’s writers seem to forget that every time you start a new medication or treatment, every time you get a new diagnosis, every time you hear the words “there is no cure,” your soul is cut into. It might heal eventually, but there will always be a scar, a reminder of the pain, the grief.

At one point in the pilot episode, Charlie, the narrator — who inexplicably speaks to the audience while in a coma — says, “Living in a hospital is sort of like going to a boarding school; you have a lot of rules but a lot of freedom.” How would he know? He’s in a coma. In fact, in hospitals there are far fewer people to interact with who are your age. In waiting rooms, parents might talk and try to seek solidarity with other patients’ parents. But most of us are focused on getting to appointments and are too worn down from treatments to form relationships with other patients. There might be a few sentences exchanged here and there, but more often than not the patients I saw didn’t talk to one another.

At the end of the pilot, Charlie says: “Everyone thinks that when you go to a hospital, life stops. But it’s just the opposite. Life starts.”

After hearing those words, I wanted to cry. Life does not start when you go to a hospital. If you’re lucky enough to have a non-terminal illness, life continues, in a warped version that includes more pain and obstacles than any young person should have to experience.


What It’s Really Like To Be Chronically Ill

What It’s Really Like To Be Chronically Ill

By:  Laura Anne, thoughtcatolog.com

Society’s recent obsession with cancer stories and movies like The Fault in Our Stars made me realize that the average person doesn’t know what it’s really like to be sick. Chronically sick. What it’s like to wake up every morning and know you’re never going to get better. No amount of medicine, doctors, surgeries, and procedures can fix you.

I think the reason why people today love to hear about cancer stories is because they are just that. They are stories. They have a beginning, middle, and an end. While that end may not be a happy one, people are satisfied with closure. But my story doesn’t have an end. And people don’t seem to like stories without an ending.

Being sick isn’t as glamorous as they make it out to be in the movies. And unlike cancer perks, there are no “chronic illness perks.” Except maybe those really good lollipops at the doctor’s office. Those are definitely a perk.

The worst part about being chronically sick isn’t the physical pain, it’s the emotional pain that goes along with it. You reach a point where you can’t hold back the tears any longer and suddenly you’re breaking down in the middle of a doctor’s office. You think you can escape the emotional torture; your disease is purely physical, right?

The worst part is that there is no escape. There is no light at the end of the tunnel. There is no happy ending. There is no way to make the incurable go away. We learn to tolerate the physical pain. You have to. But it’s the overwhelming emotional burden that makes you feel like someone is holding your head down in the water. You can fight it, but you can never overcome that crushing feeling. How are you supposed to get rid of an emotional suffocation when the source of it is never going to go away?

Being sick is being stuck in the eternal clutch of the unknown. Any day anything could go wrong, or at least more wrong than it already has. It’s so hard not to feel anxious or depressed or completely lost when all that lies ahead is a giant question mark. You rarely seem to get answers when you are sick. And when you do, they’re often the answers you wish you hadn’t heard any way.

There’s one thing every single sick person wishes for, but rarely gets. Hope. Hope that one day things will get better. Hope that there will finally be a day when your pain is a zero on that silly little scale. Hope that one day you’ll get a glimpse of normal.

I know technically being sick means my genes suck or my body just plain hates me, but somehow being sick has made me better. I may be biased, but I think that sick people — especially young sick people — are some of the best people you will ever meet. Now don’t get me wrong, healthy people are great too. But when you’re sick, you understand things that other people might take for granted.

You learn to love every good second, every good minute, of any of those few good days you might have. You don’t fear death because you’ve already stared it straight in the face quite a few times. You know it’s not important to dwell on the little things. You have more important things to worry about.

So as many times as I’ve wished to be normal for even just a day, I’ve appreciated my life, both the good and the bad, so much more as a chronically ill young person that I ever could have as a regular teenager.

Being sick makes you strong. Being sick makes you weak. Being sick gives you insight and knowledge about life as it eats away at your own. Being sick is the greatest blessing in disguise. It is so much more than just having an illness. It’s having your entire life be taken out of your control, and fighting to get it back. And that fight will never end.