Partial Acute Transverse Myelitis is a Predictor of Multiple Sclerosis in Children

Meyer et al. published a study in March 2014 about the clinical course and factors contributing to the prognosis of children under the age of 16 after they were diagnosed with acute transverse myelitis (ATM). The authors reviewed the medical records of 30 children who were diagnosed with ATM at Montpellier University Hospital in France, and follow-up records for these children were available for between 6 months and 16 years after the initial presentation. The children were split into two diagnostic categories, those with acute complete transverse myelitis (ACTM) and those with acute partial transverse myelitis (APTM). 10 of the children were categorized as having APTM, which was defined as having “…incomplete or patchy involvement of at least one spinal segment, with mild to moderate weakness, asymmetric or dissociated sensory symptoms…,” and those with bladder involvement were sometimes included. The rest of the patients were categorized as having ACTM, or “…symmetric, moderate or severe loss of function.”

Meyer et al. split the patients into these two groups because studies involving adults have found that those with APTM are more likely to eventually be diagnosed with multiple sclerosis than those with ACTM. Upon presenting to the hospital, the patients were also categorized as having:

  1. Isolated transverse myelitis, meaning that they had a normal brain MRI (53% of patients),
  2. Clinically isolated syndrome, meaning they had isolated ATM with abnormal brain MRI but no encephalopathy (17% of patients),
  3. Polyfocal CIS, meaning they had more than one lesion but that they did not have encephalopathy (13% of patients),
  4. Acute disseminated encephalomyelitis (ADEM) (17% of patients), or
  5. Multiple sclerosis (no patients).

In contrast to a previous study, none of the patients had been immunized or received an allergy shot within 30 days of their first symptoms of ATM, but in this study 60% of the patients had ATM symptoms after an infection, and 17% of the patients had a minor fall or twist before their symptoms of ATM started. At the end of the follow-up period, 5 (17%) of the patients had a diagnosis of multiple sclerosis. Having APTM was associated with a five times higher risk of eventually being diagnosed with multiple sclerosis than those with ACTM. Other studies on adults have found that patients with spinal lesions less than two sections in length are more likely to eventually have a diagnosis of multiple sclerosis than those with longer lesions, but Meyer et al. found no association between the length of the lesion in the spine and a diagnosis of multiple sclerosis. Meyer et al. attributed this to the fact that they had so few children with multiple sclerosis enrolled in their study. Furthermore, higher disability score at onset was associated with not having a subsequent diagnosis of multiple sclerosis. Meyer et al. also found that children with brain lesions were more likely to subsequently receive a diagnosis of MS than children without brain lesions. Because of this risk, and the increased risk of a subsequent diagnosis of MS in children with APTM, they suggest that children with APTM get MRI of their brain every year for at least five years.

This summary was written by Gabrielle (GG) deFiebre, Research Associate at a Public Health non-profit in New York City who was diagnosed with Transverse Myelitis in 2009. GG volunteers with the Transverse Myelitis Association.

Original research: Meyer et al. Partial acute transverse myelitis is a predictor of multiple sclerosis in children. Mult Scler. 2014; 1-9.

Transverse Myelitis Plus Syndrome and Acute Disseminated Encephalomyelitis Plus Syndrome: A Case Series of 5 Children

DeSena et al. published a paper in 2014 in JAMA Neurology describing a case series of five children (aged 29 months to 14 years) who had clinical characteristics that are not normally seen in transverse myelitis (TM) or acute disseminated encephalomyelitis (ADEM). All 5 children presented with flaccid paralysis to the University of Texas Southwestern Medical Center between 2009 and 2012 and were initially diagnosed with either TM, TM with brainstem involvement, or ADEM, but further magnetic resonance imaging (MRI) indicated that these children had inflammation in either the proximal ventral nerveroot or the cauda equina. A spinal nerve root, like the ventral nerve root, is the beginning portion of a nerve as it leaves the spinal cord and goes towards the muscles. The cauda equina is a group of spinal nerves and spinal nerve roots that innervate the pelvic organs and lower extremities, including motor innervation of the hips, knees, ankles, feet, internal anal sphincter and external anal sphincter, and sensory innervation of the perineum and some parasympathetic innervation of the bladder (source).

Nerve root and spinal nerve involvement as seen in these five children is unusual because in most cases of TM or ADEM, only the wires in the brain and/or spinal cord are affected, and not the wires after they leave the cord and go towards the muscles (there is more information about this topic a recent SRNA blog post). The nerve root or cauda equina involvement was discovered in imaging that was done after the initial diagnosis, so it is unclear if nerve root inflammation in patients with TM or ADEM represents a different disease mechanism than classic TM or ADEM, or if more people with classic TM or ADEM have nerve root involvement that was not caught in their initial imaging. Interestingly, the five cases described in this article all presented with TM/ADEM symptoms in the mid to late summer, and the authors note that this suggests that there may be a common viral or bacterial cause to these cases. Furthermore, nerve conduction studies were conducted on all five children as part of their diagnostic testing; nerve conduction studies measure nerve and muscle function in the body. Three of the patients’ nerve conduction results showed “evidence of possible axonal loss,” or damage to the nerves going into the muscles. Other studies have indicated that abnormal nerve conduction results are associated with a greater chance of incomplete motor return. The authors note that it is possible that some individuals who are diagnosed with TM and ADEM who do not recover may actually have nerve root involvement, so they suggest that all individuals who have nerve root inflammation and/or demyelination should have neuroimaging. They also argue that patients with TM who do not respond to treatment should have imaging redone to rule out nerve root involvement. The authors conclude that they believe that these patients are a separate category within the TM family of diseases, but that more studies are needed to better understand people with these clinical characteristics.

This summary was written by Gabrielle (GG) deFiebre, Research Associate at a Public Health non-profit in New York who was diagnosed with Transverse Myelitis in 2009. GG volunteers with the Transverse Myelitis Association. 

Original research: DeSena A, Graves D, Morriss MC, Greenberg BM. Transverse myelitis plus syndrome and acute disseminated encephalomyelitis plus syndrome: A case series of 5 children. JAMA Neurol. 2014; E1-E6. doi: 10.1001/jamaneurol.2013.5323

Cerebrospinal Fluid Interleukin-6 in Central Nervous System Inflammatory Diseases

Wullschleger et al. published a paper in 2013 about the role of interleukin-6 (IL-6) as a potential biomarker (https://en.wikipedia.org/wiki/Biomarker) of central nervous system (CNS) diseases. Being able to differentiate between diseases like multiple sclerosis (MS) and other inflammatory neurological diseases, like Transverse Myelitis (TM), is extremely important for a clinician to be able to do, as the treatments and disease course are different for these diseases.  It is also important because it is unlikely that there will ever be a single biomarker that can be used to diagnose MS, but there may be several biomarkers, like IL-6, that can differentiate MS from other diseases.

Cerebrospinal fluid (CSF) is thought to be one place where biomarkers related to chronic CNS diseases such as MS might be found.  Wullschleger et al. compared IL-6 levels in CSF samples of 374 individuals in several disease categories.  They tested 117 CSF samples of those with demyelinating diseases, including 76 with MS, and 30 with optic neuritis (ON).  They also tested the CSF of 10 people with idiopathic transverse myelitis (TM),35 CSF samples from people with other inflammatory neurological diseases (e.g., neurolupus), and 212 samples with non-inflammatory neurological diseases (e.g., normal pressure hydrocephalus).

IL-6 is a pleiotropic glycoprotein cytokine (a mouthful!), which generally means that it is a protein that tells cells what to do, and in particular, IL-6 mediates the communication between immune cells.  It can have differing effects on the immune system, and can cause inflammatory responses or responses that protect the nervous system.  IL-6 has been found in the CSF of people with diseases such as TM, acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica (NMO), which is why it was chosen as the biomarker for this study.  A cut-off value of IL-6 was set at 10 pg/ml, meaning any concentration above this level was considered positive for IL-6.  They found CSF to be IL-6 positive in 40% of patients with TM and 51% of patients with other inflammatory neurological diseases, but only 3.9% of MS patient samples had CSF that was IL-6 positive, and none of the patients with non-inflammatory diseases or other demyelinating diseases like optic neuritis had CSF that was positive.  Although some people with MS had CSF that was positive for IL-6, levels were lower for these individuals than for those with TM or other inflammatory neurological diseases.  As a result of their findings, the authors believe that measuring IL-6 levels in CSF should be a screening tool used to rule out MS in individuals who present with MS-like symptoms who don’t actually have the disease.

Dr. Benjamin Greenberg, Director of the TM and NMO Centers at University of Texas Southwestern Medical Center in Dallas, commented on the lack of data in this study around treatment of MS relapses in the samples that were obtained within a month of an MS relapse, and whether treatments such as steroids could influence results.  Furthermore, there was incomplete information on the 10 patients that were categorized as having idiopathic TM, which if probed further could skew data.  Further studies will be needed to confirm whether or not measuring IL-6 levels is a useful diagnostic tool for differentiating MS from other inflammatory neurological diseases.

This summary was written by Gabrielle (GG) deFiebre, Research Associate at a Public Health non-profit in New York who was diagnosed with Transverse Myelitis in 2009. GG volunteers with the Transverse Myelitis Association. 

Original research: Wullschleger A, Kapina V, Molnarfi N, Courvoisier DS, Seebach JD, et al. (2013) Cerebrospinal Fluid Interleukin-6 in Central Nervous System Inflammatory Diseases. PLoS ONE 8(8): e72399. doi:10.1371/journal.pone.0072399

CAPTURE: Instilling Hope Collectively

Recently, my son began another regimen of outpatient therapy through our regional rehab facility. We’re not new to this hospital but the PT assigned this time around was new to us. I have struggled over the past several years with communicating with various therapists, to explain and to have them understand what it is that my son is dealing with – a spinal cord injury as a result of transverse myelitis. I find some don’t want to be told info about a particular diagnosis, current research or prognosis and truthfully, that puts me off. A good therapist is going to want to know what is unique to your child and how they can help develop and meet the goals you have in mind. It’s important to his outcome that they understand he isn’t dealing with cerebral palsy and even though his “injury” was seven years ago, that there is still a need for continued therapy and it is beneficial. His time period for recovery hasn’t expired!

What struck me most about this therapist was that on one of our first visits, she said she had been researching transverse myelitis. It was the first time any therapist we have seen at this hospital had indicated they were that invested in my son; I was shocked and impressed! She then remarked about how very little information there was available about transverse myelitis – diagnosing, treatment, prognosis…and this was all coming from a professor of physical therapy! It was disturbing to hear her say this even though I know it is all too true. We had great conversation about transverse myelitis, the lack of information available, and the incredible opportunity that is right before us to begin to change the information that is available to all of those facing a transverse myelitis diagnosis.

I am sure you have heard of or seen the articles announcing the PCORI award for the first multi-center, innovative, pediatric transverse myelitis study, CAPTURE. If you haven’t, please take a moment, bookmark this entry to come back to and read a bit more about CAPTURE here! It’s okay, I’ll wait.

Now that you know about the study, I want to take a few moments to make sure you understand how you can help make this study successful and meaningful! We can’t accomplish what Dr. Greenberg et al. and SRNA have set forth to do without your help.

To be eligible as a volunteer for the study, a child does need to be newly diagnosed. The details for research volunteers can be found here. Yes, please take a moment to click this link and review the PDF – it’s important! Just be sure to come back to finish up with me here.

Perfect – now that you’re back, you’re wondering either how to sign-up or how this pertains to you if you or your child don’t fit the criteria for research?

First, if you are interested and meet the criteria, please, please, please, contact me via email or telephone and I will be happy to discuss the study further with you. You may also contact Tricia Plumb of UTSW, Research Coordinator for the study directly and she will be more than happy to answer your questions as well.

Second, if you aren’t newly diagnosed, you can still be effective and participatory. Share the letter we’ve written, the press release, and the flyer with your local physicians, hospitals, and therapists. It’s an opportunity to raise awareness and share your family’s story and how an innovative study may have helped your child and your family to overcome and work through transverse myelitis. Chances are too, that you may hear of newly diagnosed families simply via word of mouth before they ever hear of SRNA. It’s important that we reach families that have been recently diagnosed, not only for the study, but to offer our support. There is power and there is comfort in numbers. We don’t have to face this alone.

If your child has recently been diagnosed, please remember, I have been in your shoes. I know how raw, sensitive, frazzled, exhausted, confused and angry you are right now. You aren’t sure what to do next and participating in “research” is the last thing that is on your mind. Please call me. I get it. I can still feel myself in that hospital, tears streaming down my cheeks, unable to hold my infant son and simply feeling lost. If someone had walked in and asked me to participate in research, depending on the moment, they may have just received my blank stare and silent tears or the closest heavy object hurled at them. But as time moved on over the course of a few days in the acute care then rehab facility and I discovered that these physicians and therapists treating my son were themselves at a loss for all the questions and the future of my son, I wanted – no, I needed to make a change. If I understood that the foremost physicians in North America on pediatric transverse myelitis were going to review my son’s records and follow him for the next twelve months, AND hear from me as to what our life was like since his diagnosis, I would sign-up in a heartbeat.

A few key components I feel, as a parent and primary caregiver, are important and I want to make sure you are aware of:

There is a virtual cohort to this study. If you are interested but don’t know that travel to one of the participating centers is feasible, please know that there still is an opportunity for you to be involved virtually. Sometimes a family may want to but simply can’t get to one of the centers. Please know that we still want to discuss the possibility of participation in the virtual cohort.

This study is unique in that it is collaborative with the child or parents themselves. It is not strictly about clinicians gathering data from lab work or imaging but it is about quality of life from your perspective; how you or your child is feeling, coping, changing, and recovering through the year after the diagnosis.

When all is said and done with the study, we will have so much more information as to how the various treatment options affect the outcomes in more than just a clinical manner. We will have a foundation to build from for future research. And something really incredible; the results won’t be sequestered to a medical journal and only accessible by clinicians. With the help of SRNA, you can be sure that the knowledge and hope we glean from the study will be shared amongst our community so you may feel empowered and hopeful by the knowledge so you can be the best advocate for yourself or child.

I often wonder why my son wasn’t offered IVIG or PLEX, if the physicians knew about it, if it would have made a difference in his recovery…I wonder how the conversations with the physicians would have changed and perhaps may not have been so bleak when they discharged us…I wonder if the last seven years of therapy and specialist visits may have been more directed in the goals and treatment if I had access to information that gave me a better glimpse of what we were facing. Hopefully, one day, families won’t have to wonder so much and will feel enabled to be equal participants in their care.

~ Rebecca Whitney
1-855-380-3330 ext 5

Greetings from the Johns Hopkins Transverse Myelitis Center!

After getting out from under all of the snow, we have been keeping busy here in Baltimore so far this year at the Johns Hopkins Transverse Myelitis Center! Of note, recently the JHTMC was well-represented at the 2014 American Academy of Neurology, where the Center presented research on TM and other rare neuroimmune disorders. Among the research was a poster presentation entitled, “Differential Diagnosis of Transverse Myelitis,” (summary below), which was a retrospective analysis of 591 patients who presented to our Center over a 36-month period with the presumptive diagnosis of TM. We performed an in-depth analysis into the validity of patients’ diagnoses based on the available data to determine just how many patients had inflammatory TM, and determine how many actually had some non-inflammatory cause for their myelopathy. As you see from the attached results, two-thirds of patients who presented were confirmed to have inflammatory TM, and the majority of these were monophasic and idiopathic. Nonetheless, it should be noted that over a quarter of patients who presented to the JHTMC had a variety of non-inflammatory causes for their myelopathies, with the largest contenders for non-inflammatory myelopathies being attributable to compression, vascular, and metabolic etiologies. This large patient cohort alerts clinicians to recognize that the full differential diagnosis of TM is wide, and should draw attention to the fact that a comprehensive clinical work-up is necessary.

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Download Power Point by clicking on the image

The JHTMC was honored by the Academy and by Jeffrey Dunn of Stanford University by having this research selected to be highlighted at a special MS/Neuroinflammatory session, where Dr. Dunn voiced that the research represented the high level of expertise coming out of the Johns Hopkins Transverse Myelitis Center.

The following other research posters in rare neuroimmune disorders were presented by the Johns Hopkins TM team at the AAN:

  • A Note of Caution about the Diagnosis and Treatment of Suspected Transverse Myelitis where the potential negative impact of treating mimics of TM with acute therapies, specifically mimics caused by vascular myelopathies, were presented and discussed
  • Adoptive Transfer of T-cells Reactive to Aquaporin-4 Creates Neuromyelitis Optica Mouse Model that suggests that NMO is a T-cell driven disease
  • Trial of C1-Esterase Inhibitor in Acute Relapses of Neuromyelitis Optica which showed promising preliminary safety and efficacy results in our single-center open-label acute treatment trial of Cinryze for NMO relapses
  • Cytokine Disarrangement and Increased Soluble Amyloid A (SAA) in Cerebrospinal Fluid (CSF) of Patients with Neurosarcoidosis presented a promising biomarker found in the CSF that would help to differentiate neurosarcoidosis from other neuroimmune disorders including NMO, MS, and monophasic idiopathic TM

Furthermore, Differentiating NMO- and MS-Associated Optic Neuritis by MRI was selected for platform presentation. Through retrospective analysis of 55 acute optic neuritis events, we demonstrated that MRI characteristics may be a useful biomarker in NMO, since lesions are more commonly longitudinally extensive and more posteriorly-based as compared to MS. This is useful since the NMO-IgG is likely to be negative in NMO patients who present with optic neuritis alone– it is not until later that they declare themselves as truly having NMO or NMOSD, after more damage has been done. Thus, being able to discover biomarkers that can potentially be utilized early in the disease is promising!

The excitement does not stop there, however. We can barely catch a breath from AAN as we jump into June – and we are delighted to announce that this past Monday, June 9th, 2014 has officially been recognized as Transverse Myelitis Awareness Day in the State of Maryland, thanks to the dedication of our patients in working with their local senators! So it is quite fitting that we are finishing our preparations for the Johns Hopkins 2nd Annual Regional Clinical Care Transverse Myelitis Symposium, happening later in the month on June 21st right here at the Johns Hopkins Hospital. This event, which is being supported by the Bart McLean Neuroimmunology Research Fund and through an educational grant provided by Alexion Pharmaceuticals, will focus on issues patients with TM and NMO most commonly encounter, as well as the latest trends in management of these issues, rehabilitation strategies, and new and developing research in TM and NMO. We are delighted to have expert faculty and staff from Johns Hopkins Medical Institutions, International Center for Spinal Cord Injury at the Kennedy Krieger Institute, and International Neurorehabilitation Institute… and it is going to be a full house! And the weekend fun does not stop there; for those who want to make it into an entire TM/NMO weekend extravaganza, the 2014 Maryland Walk-Run-N-Roll to support SRNA is the very next day!

Never a dull moment here at the Johns Hopkins Transverse Myelitis Center!

Maureen A. Mealy, RN, BSN, MSCN
Clinical Program Manager & Research Director
Johns Hopkins Transverse Myelitis Center & Neuromyelitis Optica Clinic

Factors associated with the effectiveness of plasma exchange for the treatment of NMO-IgG-positive neuromyelitis optica spectrum disorders

Lim et al. published a study in 2013 on the effectiveness of plasma exchange (PE) in treating neuromyelitis optica spectrum disorders (NMOSDs). During plasma exchange, blood is removed from the body and the blood cells are separated from the plasma. The person receiving plasma exchange then gets their blood cells back, but the cells are mixed with donor plasma. The study included 31 women who were positive for NMO-IgG who received PE for a steroid-resistant attack of NMO. The NMO-IgG test indicates whether or not someone has antibodies for aquaporin 4 antigen, and being NMO-IgG positive is a characteristic of NMO.

In this study, 25 of the patients had an NMO diagnosis, and 6 had a diagnosis of longitudinally extensive transverse myelitis. All of the patients were characterized as moderately to severely disabled, and were given a disability score. The patients’ responses to plasma exchange were measured at 1-month and 6-month intervals after treatment with plasma exchange. Functional improvement was seen in 18 patients (58%) at 1 month and 20 patients (65%) at 6 months. Short-term improvement was associated with attacks that did not involve the optic nerve and attacks in which the patients’ reflexes were preserved. Similarly, long-term improvement was associated with non-optic nerve related attacks, but was also associated with a lower disability score at the onset of the NMOSD attack, and fewer prior attacks of NMOSD. Furthermore, improvement was seen more often in patients who did not have spinal cord atrophy than those that did. NMO-IgG levels at the beginning of plasma exchange and during the follow-up intervals were not different between those who responded favorably to the treatment and those who did not. Also, some patients received plasma exchange sooner after their onset of symptoms than other patients, but this was not associated with functional outcome. Lim et al. concluded that even though rapid onset of plasma exchange is recommended, it should be given to patients who have not recovered even after the acute phase of an attack of NMOSD.

This summary was written by Gabrielle (GG) deFiebre, Research Associate at a Public Health non-profit in New York city who was diagnosed with Transverse Myelitis in 2009. GG volunteers with the Transverse Myelitis Association.

Original research: Lim Y, Pyun SY, Kang B, Kim J, Kim K. Factors associated with the effectiveness of plasma exchange for the treatment of NMO-IgG-positive neuromyelitis optica spectrum disorders. Mult Scler. 2013; 19(9): 1216-1218.

Award from Patient-Centered Outcomes Research Institute to Study Pediatric Transverse Myelitis

The first multi-center, innovative, pediatric transverse myelitis study led by University of Texas Southwestern in Dallas, along with the Transverse Myelitis Association, Johns Hopkins Transverse Myelitis Center, Children’s Hospital of Philadelphia, Kennedy Krieger Institute, and Hospital for Sick Kids in Toronto, has recently received a research award from the Patient-Centered Outcomes Research Institute (PCORI). The study is part of a portfolio of projects that will advance the field of patient-centered comparative effectiveness research and provide patients with information that will help them make better-informed decisions about their care.

Dr. Benjamin Greenberg, MD, MHS, Director of the TM and NMO Center will lead the research project at UTSW in Dallas. The proposed study, entitled the ‘Collaborative Assessment of Pediatric Transverse myelitis: Understand, Reveal, Educate’ or CAPTURE, will be the first to combine assessments from health care providers and patients relative to pediatric TM outcomes. The collaboration will involve multiple health care centers across North America, the Transverse Myelitis Association and most importantly, patients. It will assess the current state of Pediatric TM in terms of diagnosis, treatment and outcomes. Ultimately, it will lead to an improved understanding of the current status of care for individuals afflicted with TM and reveal what are the current best practices. Patients will educate clinicians and the study will educate the broader health care system about what outcomes are important and achievable. It will develop a multi-metric outcome measure based on combined patient generated and provider generated data that can be used in future controlled trials

“Pediatric transverse myelitis is a rare potentially devastating condition that affects children of all ages. To date, there has never been a coordinated effort to understand the patient experience or clinical outcomes,” said Dr. Greenberg. “This PCORI grant is the first opportunity for an international effort to collect data about pediatric TM with an intense emphasis on patient and family reported outcomes. Working with outstanding institutions and SRNA, we plan to enroll families from around North America and gain a better understanding of this condition. Partnering with our patients and families is an exciting and welcome opportunity to make meaningful advances!”

Dr. Sanford Siegel, President of SRNA added, “The parents in our community are incredibly well educated about transverse myelitis and they are informed and effective advocates for their children’s medical care.  They are well positioned and highly motivated to make a significant contribution to the pediatric study of this rare and challenging neuro-immunologic disorder.  To date there has not been a single study or clinical trial to guide any treatment of transverse myelitis or to guide the treatment of any of the symptoms from this disorder.  The CAPTURE project represents the first study to systematically analyze the most effective acute treatments and symptom management practices in transverse myelitis.  The results of this work will have critical and far-reaching benefits for everyone who receives the transverse myelitis diagnosis.”

“This project was selected for PCORI funding not only for its scientific merit but also for its potential to fill an important gap in our health knowledge and ultimately help patients and those who care for them make more fully informed decisions about their care,” said PCORI Executive Director Joe Selby, MD, MPH. “The project reflects PCORI’s commitment to support patient-centered comparative effectiveness research, a new approach to health research that emphasizes the inclusion of patients and caregivers at all stages of the study process. We look forward to following the study’s progress and working with UTSW and the collaborating organizations to share the results.”

The study is one of 71 projects totaling more than $114 million approved for funding by PCORI’s Board of Governors on Tuesday, Sept. 10. The awards were a mix of projects that included studies specifically targeting improvement of research methods. All were selected through a highly competitive review process in which scientists, patients, caregivers, and other stakeholders helped to evaluate more than 570 proposals that responded to five PCORI funding announcements.

Proposals were evaluated on the basis of scientific merit, how well they engage patients and other stakeholders, their methodological rigor, and how well they fit within PCORI’s national research priorities. The awards are part of PCORI’s latest round of primary research funding. Through previous funding cycles, including a round of pilot projects, and other initiatives, PCORI has committed a total of $304 million since 2012 to support patient-centered comparative effectiveness research.

For more information about PCORI funding, visit https://pcori.org/funding-opportunities.

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About SRNA

The Siegel Rare Neuroimmune Association (SRNA) is a not-for-profit international foundation dedicated to the support of children, adolescents, and adults with a spectrum of rare neuroimmune disorders – Transverse Myelitis, Neuromyelitis Optica and Acute Disseminated Encephalomyelitis. Membership of SRNA includes individuals with these rare disorders, their family members and caregivers, and the medical professionals who treat individuals with these disorders. SRNA currently has over 10,500 members from more than 80 different countries and has a large number of support groups across the United States and around the world. More information is available at https://wearesrna.org.

 

About PCORI

The Patient-Centered Outcomes Research Institute (PCORI) is an independent, non-profit organization authorized by Congress in 2010. Its mission is to fund research that will provide patients, their caregivers and clinicians with the evidence-based information needed to make better-informed health care decisions. PCORI is committed to continuously seeking input from a broad range of stakeholders to guide its work. More information is available at www.pcori.org.

Reported Cases of Polio- Like Illness and its Relationship to Transverse Myelitis

By Benjamin Greenberg, MD, MHS and Allen DeSena, MD – University of Texas Southwestern, Dallas.

News reports from California have recently come out identifying a series of patients, mostly children, affected by a polio-like illness with symptoms that can mimic transverse myelitis (TM). Naturally, these reports have raised questions within our community so we thought it would be important to address some of the concerns. First, it’s important to have some background.

The spinal cord is comprised of several different pathways and cell types. Connections from the brain descend in the spinal cord and ‘attach’ to neurons in the spinal cord that then project out to muscle groups. When a person wants to move their hand, their brain sends a signal down a pathway to a set of cells within their cervical spinal cord and form a connection (a synapse). The signal from the brain activates the neurons in the spinal cord, which in turn, propagates the signal to the muscles of the hands, leading to the intended movement. This pathway can be interrupted in many ways.

Polio is caused by a virus that specifically infects the cells within the spinal cord responsible for projecting out to muscle groups (the so called lower motor neurons). When these cells die the muscles they connect to cannot be activated. Classically, transverse myelitis causes damage to the wires that are responsible for connecting the brain to these lower motor neurons, leaving the connection from spinal cord to muscle intact, but interrupting the signal that was originally meant to activate the pathway. In clinic, we tend to describe this as “wire number 1 and wire number 2”. Wire number one goes from brain to spinal cord and wire number two goes from cord to muscle. Polio damages wire number 2 and traditionally, TM damages wire number 1.

The second issue that must be addressed is the mechanism of injury. In traditional transverse myelitis a “confused” immune system inappropriately causes damage to the spinal cord. When the immune system invades the cord there is no virus there to be fought off. In the cases of patients reported from California, a virus directly infects and kills the cells. Any inflammation in the spinal cord is responding to the virus. TM is often a missed diagnosis. Sometimes this occurs because of a lack of vigilance from medical personnel, but sometimes it is because the diagnosis is unclear.  In addition, the problem with diagnosing TM is that there is no single blood or spinal fluid test that definitively identifies TM.  In addition, the spinal fluid markers of inflammatory responses cannot differentiate between an autoimmune response and a response to an infection.

Sometimes people will read that a virus has been associated with TM, but these reports are difficult to interpret. The infection could have been the inciting event but the spinal cord injury was caused by a secondary autoimmune process after the infection, or the association could have been incidental in that the patient had previously had the infection but now has an unrelated process. Also there could actually be two processes causing the spinal cord injury – both an infection-related component and a separate inflammatory component. Finally, the patient could have tested positive for the infection even though they did not have the infection at all (a false positive).  Keeping these in mind, it makes it difficult to interpret many of the case reports regarding infection and TM.  In addition, we must always keep in mind that the viruses and pathogens we do actually know about (and can test for) are a fraction of those that exist in nature, there are likely hundreds and hundreds of viruses or virus subtypes (meaning we know several but not all in a certain virus “family”) that we are not aware of.

Although we do not know the intricate details of the cases in California, the clustering of extremely similar cases in a short time frame is more suggestive of a common infectious cause, likely a virus, that has a tendency to target the same and/or closely similar areas in the spinal cord and, thus, causing similar symptoms.

In a series of upcoming papers, our team at UT Southwestern and Children’s Medical Center has described differences among patients classically diagnosed as having TM. Some of these patients have evidence of damage to BOTH wire number 1 and wire number 2. We are using these features and others to differentiate patients relative to treatment options and outcomes. In California, the public health system has identified a series of polio-like illnesses, where only wire number 2 has been affected. Some of these patients may have originally been diagnosed with TM, but in retrospect this may have been an inaccurate diagnosis. While we do not have specific case details, this is not an unexpected event given the rate of misdiagnosis of TM.

There is a virus that has been identified in some patients – a previously recognized cousin of the poliovirus – that may be the causative agent. It is also worth noting that this syndrome (viral damage to wire number 2) has been described with multiple viruses, including west nile virus. In the end, this is a reminder of the importance for improved diagnostic algorithms for patients and increased research into the world of acute paralyzing illnesses. The SRNA and the UT Southwestern/Children’s Medical Center TM program will continue to monitor events and update our community.

News articles talking about this topic:

https://www.usatoday.com/story/news/nation/2014/02/23/polio-like-illness-california/5703827

https://news.yahoo.com/polio-disease-appears-california-children-074000774.html?vp=1

https://scopeblog.stanford.edu/2014/02/24/stanford-physician-leading-efforts-to-track-emerging-polio-like-illness-in-california-children

Vote for Reg4All – an innovative project by Genetic Alliance

 

Sometimes it feels like no one is ‘listening’ to you, and your experience of living with your condition is not being considered when treatments and interventions are developed.  You may feel like no one understands how you are feeling or understands how your condition is affecting you. If there are no known effective treatments, those feelings of isolation are compounded.

Registries for All (Reg4All) is a new system that we have just launched to address these exact feelings – showing you how your experiences with your condition compare with others while letting you connect with researchers and support groups not just within your own disorder but across multiple disorders. We believe that adding your data to the larger health care puzzle will help create treatments quicker and more efficiently.

The goal of Reg4All is to bring your health online and give you the tools to determine who will see that information and how it will be used. We are working with disease advocacy groups like SRNA to bring all data under one roof. You currently answer questions about your conditions and receive instantaneous feedback on how your answers compare to others with the same condition or symptom when you sign up to become a member of SRNA. Reg4All will offer you the opportunity to connect to related researchers and support groups that align with your conditions. Reg4All will make you findable to them through your dynamic sharing preferences that match exactly how comfortable you are with sharing your health information. More importantly though, Reg4All will show you how your health condition does not have to isolate you – how there are thousands of others that are waiting to connect with and help you.

Reg4All was created by a nonprofit organization and is seeking additional funding to make the system even better.  Reg4ALL is currently competing as a finalist in a Transforming Health Systems Challenge sponsored by Ashoka Changemakers and Boehringer Ingelheim. The challenge asked for business models that disrupt and transform health systems for patients, families, and communities.  Reg4ALL does just that. We need you to help us deliver that change. Please click on this link www.changemakers.com/healthbiz and vote for Registries for All.

~ Sharon Terry, President and CEO, Genetic Alliance

 

The Johns Hopkins Transverse Myelitis Center at the AAN!

Dr. Carlos Pardo, Maureen Mealy and other members of the Medical and Scientific Committee from the Johns Hopkins Transverse Myelitis Center (JHTMC) in Baltimore, MD shared their latest research at the American Academy of Neurology meeting in San Diego in March 2013 as poster presentations.

Learn about the findings of their study differentiating inflammatory and vascular myelopathies.

Poster1

 

 

 

 

 

 

 

 

 

Below is a report characterizing the clinical and neuroimaging features of patients with sarcoidosis-associated myelopathy

Poster2