Examining Childhood Spinal Cord Disease Through a New Lens

When neurologist Dr. H.C. Bastain first introduced transverse myelitis to the medical world in 1882, he described it as a “softening of the spinal cord.” Dr. Bastain presented the autopsy findings of several patients who had already succumbed to spinal cord disease and concluded that the patients had died in one of two ways: either from a stroke in the spinal cord, in which a clot forms and the spinal cord is deprived of oxygen, or from spinal cord inflammation. These two hypotheses have lead to decades of clinical research to uncover the perplexing cause of transverse myelitis and to help patients recover from its debilitating symptoms.

Transverse myelitis today

One hundred and thirty-five years later, we still have a lot to uncover.

The current definition of transverse myelitis is a disorder that is caused by inflammation of the spinal cord. The word myelitis means inflammation, and the word transverse describes the position of the inflammation across the width of the spinal cord. This inflammation then causes demyelination. Demyelination refers to damage to the myelin sheath – a fatty substance that surrounds and protects the nerves and fibers in your nervous system. When the myelin sheath is damaged, the communication between the spine’s nerves and the rest of the body is interrupted. As a result, patients experience neurological and physical issues, such as numbness and even paralysis.

While little is known about transverse myelitis as a whole, pediatric research is particularly limited. Children with transverse myelitis tend to experience inflammation in the lower back region, causing problems with leg movement and bowel and bladder control. According to a study conducted at the Baylor College of Medicine in Texas, approximately 40-80% of pediatric transverse myelitis patients report pain as one of the earliest symptoms. The most common type of pain experienced is called neuropathic pain, which is caused by damaged nerve fibers. When nerve fibers are impaired, they send incorrect pain signals to other parts of the body that result in burning, aching, tingling, or stabbing sensations. Although neuropathic pain is seen in many transverse myelitis patients, doctors still struggle to alleviate it as the pain often responds poorly to standard treatments.

A new look at the disease

Enter Dr. Barakat, a postdoctoral fellow at the Center for Pain in the Brain research center. In her recent article published in the journal NeuroImage: Clinical, Dr. Barakat examines transverse myelitis through a new lens. Instead of addressing why the disease is occurring, she tackles how we are looking at it.

Childhood symptoms of transverse myelitis progress rapidly and there is a high risk of permanent disability. Therefore, patients and doctors need a quick and effective way to see the disease progression. But current imaging techniques for measuring demyelination are limited. Routine MRI’s are used to detect spinal cord inflammation, but they are not sensitive enough to properly assess damage to the myelin sheath. Thus, doctors and patients are left with a very restricted view of how the disease is spreading and which spinal cord pathways are being impacted.

Dr. Barakat proposes the use of two imaging techniques to uncover the full effect of spinal cord damage in transverse myelitis patients: Diffusion tensor imaging (DTI) and magnetic transfer imaging (MTI). Both techniques, Dr. Barakat argues, can be used to define the evolution of transverse myelitis, understand how the disease effects spinal cord pathways, and help create more effective treatments strategies for patients.

Diffusion tensor imaging

Diffusion tensor imaging (DTI) measures the movement of water in the spinal cord and brain. With DTI, researchers can study how nerve signals are sent up and down the spine’s tracks. Additionally, it allows scientists to analyze the structural damage of the spinal cord due to transverse myelitis.

The data from a DTI scan allows scientists to calculate fractional anisotropy, or the measurement of water movement within the spinal cord. In a healthy spine, water moves in an structured manner up and down the cord. However when the spinal cord’s myelin sheath is damaged, the water flow is no longer structured. Research suggests that the amount of reduction in fractional anisotropy may be correlated to the degree of symptoms experienced by transverse myelitis patients.

DTI scans add a level of precision to conventional MRI’s that allows for researchers to detect and map spinal cord abnormalities, thus providing a more accurate picture of the disease severity.

Magnetic transfer imaging

Magnetic transfer imaging (MTI) is another promising imaging technique for measuring spinal cord damage. Located within the center of every atom are subatomic particles called protons. All protons have an electrical charge and are associated with different molecules in the human body. In the case of transverse myelitis, researchers are interested in the interaction between protons in water molecules and lipids – more commonly referred to as fats – that form the myelin sheath. When MTI is used, energy (magnetization) is transferred from a pool of lipid molecules in the myelin sheath to a pool of unbound water molecules. This energy transfer causes a decrease in the MRI signal, which may paint an picture of the myelin sheath’s structure.

For patients with transverse myelitis, MTI can greatly improve image contrast and maximize the diagnostic potential of an MRI.

Moving forward

There is still so little known about childhood transverse myelitis. For this reason, incorrect diagnoses and poor pain management are huge obstacles for the patients and families. Current treatments focus on reducing spinal cord inflammation, alleviating symptoms, and rehabilitating individuals with permanent disabilities from the disease, but there is still no effective cure.

Dr. Barakat’s work aims to address these clinical concerns by implementing more accurate imaging techniques. Using DTI and MTI in addition to a normal MRI scan can help researchers shine a light on which spinal pathways are being impacted by the disease. This will allow doctors to develop more effective therapies to help children overcome their pain and avoid long-term disabilities. There is still a long road of research and clinical trials ahead, but uncovering the correct way to examine transverse myelitis makes the challenge far more surmountable.

Dr. Barakat works in collaboration with the Transverse Myelitis Association and the Boston Children’s Hospital Pediatric Multiple Sclerosis and Related Disorders Program with Dr. Benson and Dr. Gorman. If you are interested in participating in Dr. Barakat’s study and would like to learn more, you can view the study description here.

 

Dr. Barakat joined the Center for Pain and the Brain in 2015 as a postdoctoral fellow. She received her Ph.D in biomedical engineering with a focus on imaging pediatric traumatic spinal cord injuries. She currently is the recipient of an NIH K25 research grant and leads a team of research assistants and undergraduate students. Dr. Barakat aims to improve the health of patients with neurological disabilities by implementing more effective technologies and advanced imaging techniques. 

Helen Santoro

Posted by Helen Santoro

Helen graduated from Hamilton College in 2015 with a Bachelor of Arts in Neuroscience. She is currently involved in an fMRI study looking at children, adolescents and young adults who suffer from post-concussive headaches.

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