Research Areas
Clinical Database
Study of Pediatric and Adult Transverse Myelitis
Banking of Sera and Cerebrospinal Fluid
Recurrent Transverse Myelitis
Neuronal Markers in Transverse Myelitis
Depression in Transverse Myelitis
Magnetic Resonance Spectroscopy and Cytokine Measurements to Investigate Depression in Autoimmune Neurologic Disease
Immunopathogenesis of TM
Rehabilitation in Transverse Myelitis
Neuro-Restorative Therapies
Clinical Database: Johns Hopkins has established an extensive ongoing database. We currently have more than 450 patients with transverse myelitis, Neuromyelitis Optica (NMO) and Acute Disseminating Encephalomyelitis (ADEM). All patients referred to the Transverse Myelitis Center are given a questionnaire to complete during their initial visit. Data related to their illness, antecedent factors, clinical symptoms during the acute phase, radiologic characteristics and treatments received are gathered and entered into the database. Patients are then followed over time and their progress is charted and recorded. We are currently exploring the dataset to understand the demographics and natural course of the disease in order to characterize it further based on similarities. We are also working to understand prognostic variables and validate our diagnostic criteria. The database also serves as a clinical repository for future clinical studies and trails. As always, patient confidentiality is always respected at Johns Hopkins, and no information linking patient names to clinical data is released. All data is kept in a secure database that is protected within the Johns Hopkins network.
back to top Study of Pediatric and Adult Transverse Myelitis: Johns Hopkins is currently analyzing the information in our clinical database to study differences between pediatric and adult idiopathic (cause unknown) TM. We are seeking to answer questions such as: Is pediatric TM a clearly different entity? Can we predict the outcome of TM in a child? To date, we have about 50 pediatric cases of idiopathic TM referred to us from all over the world and about 300 adult patients who meet our diagnostic criteria. To our knowledge, this is the largest database of idiopathic cases. Disease-associated TM has a known origin, enabling a better characterization of the disease and consequent therapies. Idiopathic TM, on the other hand, is a challenge to identify and manage. We hope to be able to capture the characteristics that distinguish idiopathic TM patients who eventually recover completely, as well as those who do not.
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Banking of Sera and Cerebrospinal Fluid: Johns Hopkins has a clinical repository of blood and cerebrospinal fluid from patients both in the acute and convalescent phases of TM.
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Recurrent Transverse Myelitis: Identification of serologic markers that define and characterize transverse myelitis is important both from a diagnostic and prognostic point of view. The Transverse Myelitis Center at Johns Hopkins works closely with the Department of Rheumatology in an effort to understand the mechanisms of TM in patients with serologic or clinical evidence of connective tissue diseases such as sarcoidosis, Behcet’s disease, Sjogren’s syndrome, SLE and mixed connective tissue disorder.
A subset of our patients with TM have been found to have a recurrent transverse myelitis. Johns Hopkins has defined recurrence as the presence of more than one episode meeting the criteria for TM with intervening improvement and excluding the presence of multiple sclerosis. More than half of these recurrent cases have an unknown cause. We continue to analyze the serum of these patients for specific markers such as antibodies to the SSA antigen (also known as Ro antigen) seen in patients with primary Sjogren’s syndrome, SLE, connective tissue diseases and in babies with neonatal lupus that may be associated with a recurrent event.
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Neuronal Markers in Transverse Myelitis: Johns Hopkins has published a paper on the presence of 14-3-3, a neuronal protein, in the cerebrospinal fluid (CSF) as a poor prognostic indicator. This is an ongoing study. We have already analyzed the CSF of more than 50 patients with idiopathic TM. We are currently studying the association of the 14-3-3 with outcomes such as ambulation. We are also looking for various cytokines and other markers in order to correlate them with clinical outcome. Other studies include:
- Characterization of lymphocytes present in the CSF during the acute phase of TM.
- Examination of the capacity of CSF from the acute phase of TM patients to cause morphologic alterations and apoptosis of human cultures neurons.
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Depression in Transverse Myelitis: In association with neuropsychiatry, patients seen at the Transverse Myelitis Center are given a questionnaire, called the SCL-90, to assess the general severity index and depression among TM patients as part of their evaluation. Depression is common among TM patients and often leads to decreased compliance with physical therapy regimens and adversely affects ultimate outcome. We have also put together four neuro-cognitive tests to look for subtle cortical and sub-cortical changes that might be reflective of neuro-cognitive deficits.
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Magnetic Resonance Spectroscopy and Cytokine Measurements to Investigate Depression in Autoimmune Neurologic Disease: Jointly with the Department of Psychiatry, and funded by the General Clinical Research Center (GCRC) and the Dana Foundation, we are currently studying depression and cognitive function in transverse myelitis. TM provides a model of cytokine-mediated depression and cognitive impairment. The goal of this study is to investigate the epidemiology of these neuropsychiatric phenomena in TM subjects compared to multiple sclerosis and non-autoimmune myelopathy controls. Using neuropsychiatric evaluations, cytokine profiling and magnetic resonance spectroscopy (MRS) of TM and control subjects, we hope to elucidate cytokine elevations and brain neurochemical changes that correlate with depression and cognitive dysfunction. Subjects will be followed longitudinally to determine if changes in cytokine levels and brain metabolites parallel changes in mood, cognition and neurologic outcomes. Neuroendocrine correlates of depression in TM and MS subjects will be ascertained through examination of the function of their HPA axis.
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Immunopathogenesis of TM: Johns Hopkins is currently working on understanding the immunopathogenesis of transverse myelitis and other rare neuroimmunologic disorders. Despite considerable research, the underlying immune derangements that result in demyelinating disease with the central nervous system remain complex and incompletely understood. We are currently studying the cerebrospinal fluid and serum of patients with TM, MS and non-autoimmune myelopathies in order to be able to identify a single pathophysiologic mechanism that leads to tissue injury in TM.
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Rehabilitation in Transverse Myelitis: Rehabilitation is an integral part of the recovery and treatment of TM patients. The Johns Hopkins TM team works closely with the Physical Medicine and Rehabilitation team to constantly assess and seek effective rehabilitation measures and management. Patients are often left with permanent weakness and spasticity, which limits the extent of recovery. Patients often report stiffness, tightness or painful spasms in the buttocks and legs.
Ongoing projects include spasticity evaluation and treatment with new drugs such as tiagabine and use of a tone assessment device for formal functional gait assessment, intervention spasticity management with the Baclofen pump and use of 4-AP (fampridine) in the functional improvement of TM patients.
The Johns Hopkins Tone Measurement and Biomechanics Lab, located with the Motion Analysis Labs at the Kennedy Krieger Institute, focuses on quantitative measurements associated with movement disorders. Two of the devices applied are the Lower Limb Spasticity Measurement System (LLSMS) and the GAITRite Portable Walkway System.
The LLSMS was developed in the late 1980s at the University of Washington (Robert Price MSE, Justus Lehmann , MD and Barbara de Lateur MD) to quantitatively measure, around the ankle, passive qualities of the muscles such as muscle tone, which is the muscle’s resistance when stretched. The subject relaxes prone on an adjustable bed with the tested foot fitted into the LLSMS boot which oscillates across a frequency range for about a five to ten-minute period. The LLSMS oscillates the ankle joint in a sinusoidal motion at a fixed range of motion of five degrees within a frequency range of three to 12 Hz. A computer measures the muscle’s torque response (passive stretch and resistance) as the ankle is moved in the controlled pattern. To ensure that only the passive (non-voluntary and non-reflex) qualities of the muscle are measured, the muscle’s electromyography (EMG) is monitored and recorded using two surface (no needles) electrodes.
Muscle tone, or resistance to a passive stretch, is modeled mathematically using viscoelastic parameters. Elastic and viscous stiffness are two such derived values, which are plotted against each other across the range of frequencies to produce a total stiffness vector in a Nyquist Diagram. The measured relationship is represented by a single outcome measure of tone called the total pathlength. In general, the Nyquist plot appears as a reverse C that becomes more open or longer in vector length with increased spasticity or hypertonia; thus, the increase in the total pathlength value. Over the years the LLSMS has been used to obtain a quantitative measure of spasticity.
The GAITRite Portable Walkway System has been commercially available from CIR Systems, Inc. for several years as an economical tool used internationally to obtain quantitative gait parameters. The walkway is a thin, roll-up vinyl carpet encapsulating an active grid area of two by 12 to 24 feet. The 40-pound, 12-foot carpet has 13,824 pressure sensors placed at 0.5-inch centers. The portable pad or carpet lies over a flat, non-slope, solid surface and connects to a laptop with easy setup and operation. The minimum testing area is five feet wide by 35 feet long, allowing for a walking assistant, and five foot acceleration and deceleration zones with added turn-around area. Input data includes the gender, height, weight, and right and left leg lengths (used in normalized computations).
As the subject ambulates across the walkway, the system captures the relative arrangement, geometry, and applied pressure of each footfall as a function of time and derives objective spatial and temporal parameters along with their coefficient of variation. Data is stored in an Access database and a variety of individual and group analyses and reports are possible along with progress comparisons to self and normal values.
The system can test subjects with or without shoes and allows the use of assistive or ambulatory aids, such as crutches, canes, or walkers. Outcome measures differentiated as right and left include step, cycle, swing, and stance time; velocity; cadence; step and stride length; H-H dynamic base, single, and double support; toe in and out degrees; step/extremity ratio; and the functional ambulation aerformance (FAP) score. These measures give quantification of walking speed, stride length, step length, symmetry, base width, and consistency from step to step along with the variability from stride to stride (heelstrike of one side to heelstrike of the same side). As for the FAP score, it was developed and tested in a number of studies of normals and neurologically impaired subjects and published as a single score of gait to objectively measure the efficacy of treatments. The score is based on the ratio of step length to leg length to step time and factors in bilateral asymmetries. Reports include detailed color representations of the footfall pressure distribution and the associated gait pattern.
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Neuro-Restorative Therapies: Johns Hopkins believes that restorative therapies hold great promise in allowing patients to recover from paralysis. In some cases, these therapies are restricted to the acute phase of paralysis when the “cues” to guide regeneration of neural circuits exist endogenously. In other cases, the endogenous cues to guide restoration of function no longer exist, as in a patient who was paralyzed in the distant past. Recently, we have learned to direct neural stem cells to become motoneurons and we believe we can direct them to establish connections with muscle. Therefore, we believe that restoration of function is possible. We will work toward advancing these treatments toward clinical trials designed to restore function of paralyzed patients. Click here to see Doug Kerr and Adam Kaplin discuss this exciting work.
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