Genetic Mutation Found in Familial Transverse Myelitis

By Dr. Michael Levy

Associate Professor of Neurology at the Johns Hopkins Hospital and Medical Director of General Neurology at the Johns Hopkins Hospital in Baltimore, MD

We found a rare genetic mutation in some families of patients with acute transverse myelitis (TM) that may provide new insights into the disease process. Two sisters with TM came to our attention through SRNA who agreed to donate their DNA for a thorough genetic analysis called exome sequencing. Only one meaningful difference was found in both sisters, which their two healthy brothers did not have: a mutation in a gene called VPS37A. As it turns out, a genetic mutation like theirs is extraordinarily rare in nature. No other known organism in the animal kingdom has this mutation so we thought this could be biologically important. But we didn’t know how common this was. With the help of SRNA, the Accelerated Cure Project and collaborators at Johns Hopkins, we screened an additional 86 TM patients and found another patient with the same rare mutation! It is statistically beyond coincidence to find three human beings with this same rare genetic mutation unless it has something to do with the rare disease they all share, TM. We do not yet understand how this gene, or the genetic mutation, is associated with TM. But with the continued support of SRNA, funding agencies and of course, our TM patients, we are beginning to piece this puzzle together.

The abstract below was presented at American Academy of Neurology 2017 in Boston, MA.

Maureen Mealy¹, RN, Tai-Seung Nam², MD, PhD, Santiago Pardo¹, Carlos A. Pardo¹, MD, PhD, David Valle³, MD, Kathleen Burns³,⁴, MD, PhD, Michael Levy¹, MD, PhD

1.     Department of Neurology, Johns Hopkins University, Baltimore, MD, USA

2.     Department of Neurology, Chonnam National University Medical School, Gwangju, South Korea

3.     Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA

4.     Department of Pathology, Johns Hopkins University, Baltimore, MD, USA

Background. Idiopathic transverse myelitis is an acute inflammatory attack of the spinal cord leading to weakness, sensory loss and bowel/bladder dysfunction. The prevalence is 0.1-0.2/100,000 and there are no known risk factors.

Objective. To identify a genetic risk for development of idiopathic transverse myelitis.

Methods. We identified two sisters who both have idiopathic transverse myelitis, and compared exome sequencing on DNA samples from them with two healthy siblings. We also sequenced 200 additional samples from patients with idiopathic transverse myelitis, multiple sclerosis, neuromyelitis optica, other neurological conditions and healthy controls.

Results. The two sisters with idiopathic transverse myelitis both had acute onset of sensory loss in the legs, followed by weakness and bowel/bladder dysfunction. The first sister developed myelitis at age 15 with clinical nadir of complete paralysis. Over the next few years, she recovered her ability to walk without assistance. Recent MRI demonstrated persistent T2 lesion in the lower thoracic cord. The second sister developed myelitis at age 50 with nadir of complete sensory loss from T6 down and paraparesis in the legs, associated with an MRI lesion at T6. She also made a partial recovery with treatment. Both sisters share a non-synonymous homozygous mutation in only one gene, VPS37A (c.700C>A, p.Leu234Ile) in the whole genome analyses. One healthy sibling was heterozygous for this mutation. We screened an additional 261 samples from patients with ITM and neuroimmunological diseases by Sanger sequencing of this portion of VPS37A and identified another idiopathic TM patient with this same rare homozygous mutation. No patients with multiple sclerosis, neuromyelitis optica, other neurological conditions or healthy controls contained a homozygous mutation in VPS37A.

Conclusions. A mutation in VPS37A may predispose to development of idiopathic transverse myelitis. Further studies are necessary to determine the frequency of this mutation in this patient population and how this genetic mutation might contribute to risk of disease.

Acute Disseminated Encephalomyelitis (ADEM): Past, Present, and Future

Cynthia Wang, MD

James T. Lubin Fellow at the University of Texas Southwestern Medical Center in Dallas

Acute disseminated encephalomyelitis (ADEM) is a rare, autoimmune neurological condition that often occurs in young children following an infection. Initial symptoms of ADEM may be quite variable and non-specific, including headache, fever, irritability, confusion, sleepiness, and weakness. Over the years, our understanding of ADEM has matured, though many aspects of the condition remain mysterious. What leads some individuals to develop the condition in the first place? Could it happen again? Why do some individuals make a full recovery while others have lasting impairment?

ADEM is thought to develop when the body mounts a response to an infection, but rather than solely attacking the invading organism, it mistakenly targets parts of the nervous system as well. ADEM is primarily a clinical diagnosis, meaning that we do not have a perfect test that can tell us definitively whether a child or adult has ADEM. Laboratory studies of blood and spinal fluid, and MRIs of the brain and spine can help rule out other conditions and support the diagnosis of ADEM. If ADEM is suspected, children and adults often receive steroid medications during their hospitalization to help reduce inflammation and suppress the body’s confused immune system.

For the vast majority of those affected by ADEM, it is a one-time illness and does not recur. Many children make excellent recoveries and largely seem to return to normal. However, episodes of new neurological symptoms, especially those that develop 3 months or more after the initial event, raise concern for an alternate diagnosis, such as multiple sclerosis or neuromyelitis optica spectrum disorder. In our clinic at UTSW Dallas, our practice has been to repeat MRI brain scans at 3-4 months after ADEM to establish a baseline for future comparison. Any new clinical events or MRI brain lesions occurring after this period of time would lead to scrutiny of the ADEM diagnosis

Another practice in our clinic is to perform neuropsychological testing on our patients who have had ADEM. Increasing research highlights that children with ADEM may have subtle cognitive deficits involving processing speed, visual-motor integration, executive functioning, language processing, and behavioral regulation that may not be evident until they get older and are faced with increasing academic and social demands. Neuropsychological testing is geared toward uncovering areas of weakness and may be helpful in guiding school accommodations for children affected by ADEM.

We are just beginning to study the long-term outcomes of children with ADEM, particularly their cognitive potential, academic achievement, social functioning, and quality of life. In the past couple of years, we have also learned more about a subset of ADEM patients who make antibodies toward a protein on the outer surface of certain cells called myelin oligodendrocyte glycoprotein (MOG). Over time, our ability to test for this antibody has improved, along with increasing understanding that this group of MOG positive ADEM patients may have similarities in their clinical presentation, neuroimaging, and prognoses that may impact their care.


Introducing APERTURE: Assessment of Pediatric and Adult Encephalomyelitis Related Outcomes: Understand, Reveal, Educate

To help address gaps in our understanding about ADEM, our group at University of Texas Southwestern Medical Center will be conducting a study examining the long-term outcomes of individuals with ADEM. We aim to collect data on a large group of children and adults diagnosed with ADEM and review their presenting history, laboratory studies, neuroimaging, treatment course, and recovery from ADEM. Individuals between ages 0-64 with the initial diagnosis of ADEM are welcome to participate. People who cannot travel to our center in Dallas can participate remotely by providing medical records, MRI studies, completing questionnaires, and in some cases, neuropsychological testing. Enrollment will begin in June 2017.

We are eager to learn more about this rare neurological condition, and with your help, work toward improving our ability to better care for those affected by ADEM.

Please email [email protected] for more details.

Currently Enrolling NMOSD Clinical Trials

Conducting research through clinical trials is one of the ways we develop and identify new therapies and learn what the best treatments are for rare neuroimmune disorders. There are three clinical trials that are currently enrolling patients with neuromyelitis optica spectrum disorder (NMOSD). We have included a summary of all three studies below. For more information on clinical trials, click here.


Alexion Pharmaceuticals, Inc. is conducting a clinical trial called the PREVENT Study. The primary objective of the study is to assess the efficacy and safety of an investigational medicine as a potential treatment to prevent relapses in NMO and NMO Spectrum Disorder (NMOSD).

This is a randomized double blind study, where participants will receive investigational medication or placebo and neither the participant nor the study doctor or their staff will know who received the drug or placebo. In this study, 2 out of 3 participants will receive investigational medication and 1 out of 3 participants will receive placebo. The medication is given intravenously at the study doctor’s office or infusion center.

Participants may be eligible if they are at least 18 years old, have a positive test for the NMO-IgG antibody and have experienced 2 relapses in the past 12 months or 3 relapses in the last 24 months with at least 1 relapse in the last 12 months.

This is an “add on study,” and patients may be able to continue taking their current NMO or NMOSD medications and receive the study medication.

There are known and unknown potential side effects, which will be discussed prior to enrollment and detailed in the informed consent. For more information, email: [email protected]

N-Momentum Study

Medimmune is currently conducting the N-Momentum study, a clinical research trial in subjects with NMOSD. The trial is actively recruiting seropositive and seronegative NMOSD patients around the world. The main objective of this study is to determine if inebilizumab (formally known as MEDI-551) compared to placebo can significantly delay the time it takes for a new NMO/NMOSD attack to occur.  The trial will recruit 252 NMOSD subjects from approximately 100 sites in 25 countries, 67 confirmed adjudicated NMOSD attacks are needed to determine if inebilizumab is effective compare to placebo.

This is a multinational randomized, double-masked, placebo-controlled study with an open‑label period. Eligible NMO/NMOSD patients will be “randomized” in a 3:1 ratio to received either MEDI-551 or placebo. This random selection will give a 25% (1 in 4) chance of getting placebo and a 75% (3 in 4) chance of getting Inebilizumab.

This trial enrolls seronegative and seropositive NMOSD patients. After being enrolled in the study, subjects are followed for 28 weeks in the placebo-controlled treatment period where inebilizumab or placebo will be given by an intravenous infusion on Day 1 and Day 15. During the study, no additional immunosuppressive therapy will be allowed.

Patients will have the option to enroll into the open-label period if a confirmed NMOSD attack occurred during the placebo-controlled treatment period. Subjects who complete the placebo-controlled treatment period without experiencing an attack will also be given the option to enroll in the open-label period. During the open-label period, inebilizumab will be given on Day 1 and Day 15 and then every 6 months thereafter until the end of the study.

As of April of 2017, 141 NMOSD subjects have been enrolled in the study of which 130 are AQP4 seropositives and 11 are AQP4 seronegatives.

If you are interested in participating, please contact: the AstraZeneca Clinical Study Information Center at 1-877-240-9479 or email [email protected]

SA237 Study

This research is being conducted to evaluate the efficacy, safety, pharmacodynamic, pharmacokinetic and immunogenic profiles of a humanized anti-human IL-6R neutralizing monoclonal antibody (SA237) in patients with Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD). This study is being conducted in the US and Canada and will enroll seventy (70) patients to participate in this research.

SA237 is a humanized anti-human IL-6R neutralizing monoclonal antibody that was designed by applying recycling antibody technology to the approved anti-IL6 receptor antibody, tocilizumab, which is currently marketed as a treatment for rheumatoid arthritis (RA), systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis and Castleman’s disease. The recycling antibody technology enabled SA237 to bind to IL-6 receptor multiple times and be slowly cleared from plasma, which is expected to contribute to improvement and is convenient with once monthly dosing frequency. The longer plasma half-life of SA237 compared with tocilizumab was confirmed based on the results of a non-clinical study and a Phase 1 study in healthy volunteers.

Individuals who have NMO or NMOSD and are between the ages of 18 and 74 years may be eligible.

If you are interested in participating, please email [email protected]

Queen’s University researchers make major myelin repair discovery

Queen’s University Belfast scientists have discovered that specific cells from the immune system are key players in repairing myelin in the central nervous system – a fundamental breakthrough that could revolutionize the treatment of debilitating neurological disorders such as multiple sclerosis (MS) and many demyelinating conditions such as transverse myelitis, neuromyelitis optica spectrum disorder and acute disseminated encephalomyelitis. In all these conditions, the myelin is damaged, and there are immune cells present at many sites of damage in the central nervous system. Myelin is important because without it, nerves are not able to conduct or send signals where they need to go.

The research study, led by Dr Yvonne Dombrowski and Dr Denise Fitzgerald at the Wellcome Wolfson Institute for Experimental Medicine at Queen’s University Belfast, is being hailed as a landmark study in unravelling the mysteries of how the brain repairs damage.

The research breakthrough, which was published in Nature Neuroscience, shows that a growth regulatory protein made by certain cells within the immune system, called regulatory T cells (Treg), triggers the brain’s stem cells to mature into oligodendrocytes, which are cells that repair myelin. What the Fitzgerald group and collaborators have discovered in different settings of myelin damage (including spinal cord and brain tissue), is that this specific immune cell, Treg, is critical for driving efficient repair of myelin. The Tregs accomplish this by producing a protein, CCN3, that triggers immature oligodendrocytes to mature, start producing myelin, and re-wrap nerves.

They studied this using a focal demyelinating mouse model induced by injecting lysolecithin into spinal cord white matter. They confirmed their findings with a second demyelinating model at a different central nervous system site using another drug called cuprizone. Further, in brain slice cultures, they were able to show that Tregs promoted brain tissue myelination and remyelination in the absence of inflammation. The discovery means that researchers can now use this new knowledge to develop medicines which will boost these particular cells and develop an entirely new class of treatments for the future.

Senior author of the study, Dr Denise Fitzgerald from Queen’s, was diagnosed with transverse myelitis when she was 21 and had to learn to walk again. Commenting on the findings, Dr Fitzgerald said: “This pioneering research, led by our team at Queen’s, is an exciting collaboration of top scientists from different disciplines at Cambridge, San Francisco, Edinburgh and Nice. It is by bringing together these experts from immunology, neuroscience and stem cell biology that we have been able to make this landmark discovery. This is an important step forward in understanding how the brain and spinal cord are naturally repaired and opens up new therapeutic potential for myelin regeneration in patients. We continue to work together to advance knowledge and push the boundaries of scientific knowledge for the benefits of patients and society, in a bid to change lives for the better, across the globe.”

Original Research: Dombrowski Y, O’Hagan T, Dittmer M et al. Regulatory T cells promote myelin regeneration in the central nervous system. Nat Neurosci. 2017 Mar 13.

Collaborative Meeting on Acute Flaccid Myelitis

On January 23, 2017 SRNA cosponsored a collaborative meeting on acute flaccid myelitis (AFM) that was hosted by the CONQUER Program of UT Southwestern and Children’s Health Dallas. Twenty-four health care providers, researchers, Centers for Disease Control (CDC) representatives, and SRNA participated in this meeting. The purpose of the meeting was to bring stakeholders together to compare data and experiences about AFM, learn about the initiatives led by different stakeholders, review the current case definition and identify research needs and potential collaborations.

Here are the top ten takeaways from the AFM meeting:

  1. Dr. Benjamin Greenberg of UT Southwestern started the meeting by giving a background about AFM, including the history of the disorder. He emphasized that AFM has likely been around for many years, but that we are only now aware of it and are describing it as AFM.
  2. There remains some ambiguity on the case definition of AFM that gets reported to the CDC, but researchers and medical professionals are working hard to come to a consensus about this. Dr. Sarah Hopkins from the Children’s Hospital of Philadelphia shared her experience as a case reviewer for the CDC and at CHOP, and that imaging interpretation continues to be difficult with regard to involvement of gray matter and the timing of the MRI.
  3. Dr. Manisha Patel from the CDC discussed the number of AFM cases that have been reported to the CDC. There were fewer cases reported in 2015 than 2014.
  4. Dr. Thomas Briese from Columbia University Medical Center discussed the role of enterovirus D68, a virus that is capable of causing an infection in the central nervous system. Enterovirus D68 may be a factor in recent clusters of AFM.
  5. Dr. Carol Glaser from Kaiser Permanente and Dr. Avi Nath from the National Institutes of Health shared their views on whether or not enterovirus D68 could be a cause of AFM, and came to the conclusion that there was significant data linking EVD68 to AFM, but more research would be useful.
  6. Dr. Ken Tyler and his team from the University of Colorado have developed an animal model of AFM that will hopefully help researchers better understand the mechanisms behind AFM.
  7. Dr. Teri Schreiner from the University of Colorado reported findings from a study on outcomes after pediatric AFM. She found that all the children they followed improved functionally but continue to have limb weakness.
  8. Dr. Greenberg reviewed the CAPTURE study which is an ongoing study in pediatric transverse myelitis, including AFM, which will hopefully help us better understand this disorder.
  9. While the CDC does not currently recommend IV steroids, IVIG, or plasma exchange (PLEX) in the treatment of AFM, some physicians treating patients with AFM have seen improvement in their patients with these treatments. Currently, there are no data or consensus to systematically guide treatment in AFM. Treatment decisions should be individualized and based on the clinical characteristics of each patient.
  10. Determining the proper diagnostic tests and the correct timing for these tests is critical to improving the care and treatment of people with AFM.

Overall, the meeting was an excellent opportunity to learn about what is currently being done to better understand AFM, to improve the case definition, and improve diagnosis and treatment options. It was a great step in building collaborative approaches to addressing this growing public health concern. We look forward to sharing more updates with the community as we learn more.

Aquaporin 4 IgG Serostatus and Outcome in Recurrent Longitudinally Extensive Transverse Myelitis

Neuromyelitis Optica is an autoimmune disorder that affects both adults and children commonly causing severe recurrent bouts of optic neuritis and transverse myelitis. Patients often present with either optic neuritis or transverse myelitis only to have future relapses confirming the diagnosis of NMO. In 2004 an antibody was identified in a large number of NMO patients. This antibody recognized the AQP4 protein in astrocytes (a specialized cell in the central nervous system). Patients with this anti-AQP4 antibody have been shown to develop NMO when followed over time, but initially many patients tested negative for this antibody. In this scenario, scientists often question, do patients who test negative lack the antibody or is the test not sensitive enough to identify them?

Dr. Pittock’s group from Mayo Clinic recently published their original work focused on recurrent longitudinally extensive transverse myelitis (rLETM). The goal of the study was to study AQP4-IgG, a known clinical biomarker of NMO spectrum disorders, from patients with rLETM using a recombinant human AQP4 based assay who were initially classified as negative for this antibody based on an assay known as IIF. The authors did a search of the Mayo Clinic database based on diagnosis from Oct 2005 to Nov 2011 and identified 48 patients with rLETM, 75% of whom were positive for the NMO signature of AQP4 IgG using the IIF method with serial serum specimens. On retesting those that were negative using the recombinant human AQP4-based assays, the overall AQP4-IgG seropositivity increased from 75% to 89%.

The authors also set out to define the clinical characteristics and motor disability outcomes in those who were positive for AQP4 IgG. This study showed that 36% of rLETM patients who were seropositive will likely need a cane to walk within 5 years after onset, and the median time from onset to first optic neuritis attack was 54 months in those who went on to be diagnosed as NMO. The median number of acute attacks was 3 in those rLETM patients who were seropositive (ranged from 2-22 attacks). Immunosuppression reduced the relapse rate in both seropositive and seronegative rLETM patients.

The authors concluded that recombinant antigen based assays can better detect AQP4-IgG in rLETM patients and generally adults with rLETM are seropositive, and are likely to go on and be diagnosed as having NMO. For rLETM patients who are at higher risk to convert to NMO, testing for this antibody AQP4 using more sensitive assays is the recommendation of the authors if less sensitive tests show negative results.

Original research article: Jiao Y, Fryer JP, Lennon VA et al. Aquaporin 4 IgG serostatus and outcome in recurrent longitudinally extensive transverse myelitis. JAMA Neurol. 2014;71(1):48-54. doi:10.1001/ jamaneurol.2013.5055

Bladder Management Research Study Opportunity

The research teams at the Universities of Michigan, Minnesota, and Utah have created a study to examine how patients feel about their bladder management options. They hope to discover not only what does and does not work, but how to provide better care for people with spinal cord injuries in the future. Participants must have a spinal cord injury or problem that was acquired during their life (for example, transverse myelitis) and not something that occurred at birth.

Impact of Autologous Mesenchymal Stem Cell Infusion on Neuromyelitis Optica Spectrum Disorder: A Pilot, 2-Year Observational Study

Bone marrow-derived mesenchymal stem cells, or MSCs, are a type of stem cell that can differentiate, or turn into other types of cells. They are taken from a patient’s own bone marrow. They have been used in several autoimmune diseases, including multiple sclerosis. MSCs can repair tissue and also inhibit the immune system, offering a potential treatment for neuromyelitis optica spectrum disorder (NMOSD). MSCs are given through an infusion.

Researchers recruited participants between September 2013 and January 2015. Participants were individuals with a diagnosis of NMO (based on criteria from 2006; diagnostic criteria were recently updated and can be found here), or with either recurrent optic neuritis or longitudinally extensive transverse myelitis and who were anti-AQP4 antibody positive. They were assessed at baseline, which was the day before treatment with MSCs, and 1, 3, 6, 9, and 12 months after treatment. The researchers looked at functional and structural outcomes. Functional outcomes were a scale (EDSS) that measures disability, a visual acuity test, and a cognitive test called the Paced Auditory Serial Addition Test (PASAT). Structural outcomes were MRIs of the optic nerve, brain, and spinal cord, and optical coherence tomography (OCT), which looks at the retina. They looked for relapses, which were new or recurrent neurological symptoms that lasted at least 24 hours. These symptoms were not counted if they were because of fever or infection. To be counted as a relapse, there had to be at least 30 days of separation from a previous episode. They also looked at the safety of the MSC treatment.

The study included 15 patients, with an average age of 47 years. Most (87%) participants were anti-AQP4 antibody positive. All of them had failed a different treatment prior to the study, meaning they had had at least one attack after receiving treatment. These prior treatments were cyclophosphamide or azathioprine, with or without steroids.

The MSC treatment did not cause side effects for most participants. Only one patient developed a low-grade fever and knee pain after the treatment, but these symptoms went away after treatment was completed. Weekly blood tests after the treatment were normal and no participants developed tumors within one year of treatment.

Twelve patients had no relapse at 12 months after MSC treatment, and three had at least one relapse. The relapses were mild. Their disability scores did not get worse and their symptoms went away after a month. The average annualized relapse rate was significantly lower after MSC treatment. Also, there were significantly fewer lesions in the optic nerve and spinal cord after treatment. The average disability score was also lower, and there was improvement in visual acuity and cognition. They had increased retinal nerve fiber layer thickness, optic nerve diameter, and upper cervical cord area. Three months after treatment, levels of anti-AQP4 antibodies decreased, but these levels went back to baseline again at 6-12 months. During the second year of the study, 13 participants were relapse free. Like the first year, the average annualized relapse rate was lower than before treatment and the average disability score was also lower than before treatment.

This small study did not have any obvious, serious, adverse events and supports an investment in larger controlled studies to understand the potential benefit of MSC treatment for NMOSD.

NMO spectrum disorders: clinical or molecular classification?

The International Panel for NMO Diagnosis (IPND) released an updated set of guidelines for diagnosing Neuromyelitis Optica (NMO) and Neuromyelitis Optica spectrum disorders (NMOSD) in 2015.  We published a summary of the updated guidelines earlier on SRNA Blog. Diagnostic criteria for AQP4-IgG-positive NMOSD, NMOSD without AQP4-IgG or with unknown AQP4-IgG status were established, along with a set of core clinical characteristics to aid in diagnosing those with potential NMOSD. Anti-AQP4 antibodies affect the nervous system in a very specific way that is different from other auto-immune disorders to cause damage.

Another article by Uzawa et al. described the use of these guidelines in four NMOSD patients who were negative for AQP4-IgG. They found that the new criteria would be useful for more accurately diagnosing NMOSD earlier in patients. In this article, Dr. Pittock discussed Uzawa et al.’s findings and talked about the potential issues with diagnosing someone with NMOSD. He stated that what we call NMOSD might actually be several different diseases that we don’t understand enough about to identify them as different diseases. For example, the four NMOSD patients in Uzawa’s article though classified as NMOSD, had different symptoms, their MRIs looked different from each other, and their lab findings varied. Also, the way the immune systems of anti-AQP4 antibody positive individuals attacks itself is different from how the immune systems of people who are AQP4-negative attacks itself. By using symptoms and MRI findings to diagnose people with NMOSD, physicians might be clumping together people with different disorders that have different causes, prognosis, and different responses to treatment.

Pittock states that as more biomarkers are discovered, it might make more sense to name diseases based on the biomarker associated with them. Other autoimmune neurological diseases have done this when biomarkers have been found. He suggests using “autoimmune AQP4 channelopathy” instead of NMOSD. He also thinks that by classifying diseases in this way, it will be helpful as medications that target the specific immune process for each disease are developed.

Diagnosing Transverse Myelitis

Paula Barreras Cortes, MD
Postdoctoral Fellow
Johns Hopkins Transverse Myelitis Center, Baltimore, MD

Many patients struggle through the initial evaluation before receiving a transverse myelitis (TM) diagnosis. A primary focus of the TM Center at Johns Hopkins University School of Medicine (JHTMC) is to facilitate a precise diagnosis and treatment for TM. It is not infrequent that some patients are initially misdiagnosed and treated for conditions that they don’t have. Many patients are given diagnoses, such as Multiple Sclerosis, Guillain-Barré syndrome (GBS) or even psychogenic problems before reaching a final diagnosis of TM.

Some of these issues are caused by a lack of understanding among some doctors in the community about TM and the diagnostic approaches required for patients who are experiencing symptoms suggestive of this disorder. This problem is further complicated when patients are dismissed and sent home from emergency departments or when patients need multiple visits or even multiple hospital admissions before obtaining a final diagnosis. Additional delays are created when patients are forced to find practitioners familiar with TM. All of these complications and delays ultimately postpone the correct treatments, almost all of which should be administered as quickly as possible.

One of the most important missions of the JHTMC is to identify better ways to improve the diagnosis of TM and to disseminate the strategies that would help doctors make a proper diagnosis from the very beginning. We have focused on studying the factors that may influence misdiagnosis and erroneous treatment. We are also interested in the identification of the factors that influence relapses and the outcomes of the disorder.

In one of our recent studies, we analyzed more than 500 clinical records from patients referred to the JHTMC for evaluation of TM. In our study, we found that nearly 40% of the patients were erroneously diagnosed as TM when they really had other problems, such as strokes, herniated disks, tumors and metabolic problems that affected the spinal cord. Not surprisingly, a high percentage of the patients that were properly diagnosed were also initially misdiagnosed as GBS or other neurological disorders. These findings immediately point out a lack of understanding of TM and a lack of understanding of the disorders that present with similar symptoms to TM but are not TM. As part of our study, we analyzed the presentation pattern of TM. By combining clinical information, the time-frame of clinical presentation, the findings of imaging of the spinal cord by magnetic resonance imaging and the results of the cerebrospinal fluid, we have been able to identify clinical profiles that facilitate an approach to achieve an accurate diagnosis of TM and differentiate TM from other disorders that may mimic TM. When looking at the factors that best predicted who really had TM versus other diagnoses, two things came up as the most important ones: the temporal profile of symptom presentation and the features of the first MRI of the spinal cord. The time from the onset to the peak of symptoms correlated with the diagnosis, as most strokes of the spinal cord occurred very fast (i.e., in a couple of hours), while the truly inflammatory problems took several hours to days to establish. The localization of the lesion in the MRI was also very helpful: the strokes of the spinal cord were more frequently located in the anterior part of the cord and were longer than the myelitis lesions.

We hope this information is useful to doctors in the community and for our patients to help with a proper diagnosis.  If we are able to avoid confusion between a diagnosis of TM and other problems of the spinal cord, we can avoid unnecessary and potentially harmful treatments, while offering the proper treatments as quickly as possible.