Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized pathologically by demyelination and axonal injury. Conventional magnetic resonance imaging (MRI) techniques are extremely sensitive to changes associated with inflammation (free hydrogen protons), but do not adequately capture the pattern of demyelination and axonal loss that occur in the brain and spinal cord, thus there has been discordance between clinical disability and MRI lesion load. Demyelination and degeneration of axons are important pathogenic mechanisms of damage in MS. However, attempts at correlating clinical disability with demyelination and axonal injury have had limited success due to clinical rating scales that do not adequately measure all aspects of the disease, coupled with the inability for routine imaging techniques to depict specific clinically involved fiber tracts in the brain and spinal cord.
In this project we plan to capitalize upon the strengths of our motion laboratory, which can measure spasticity, ataxia, sensation, and muscle strength that contribute to impaired locomotion, in conjunction with advanced Magnetization Transfer (MT) and Diffusion Tensor imaging (DTI) metrics developed at the Kirby Imaging Center of the Kennedy Krieger Institute. The proposed studies will test the hypotheses that: 1) during an acute exacerbation, specific, MRI-demonstrable, white matter tract abnormalities will predict specific sensory, strength, spastic, or ataxic impairments that result in specific locomotor patterns, and 2) The pattern and extent of demyelination and axonal injury as measured by MT and DTI in the corticospinal tract, dorsal column-medial lemniscal tracts and cerebellar peduncles can predict the recovery of sensorimotor impairments and locomotion after a relapse of MS.
1. To determine the contribution of specific white matter tract abnormalities to specific sensory, strength, spastic or ataxic impairments, and how they contribute to locomotor patterns during an acute exacerbation of MS.
2. To determine what extent pathological recovery (i.e., MT measures of demyelination and DTI measures of axonal integrity) is associated with recovery of locomotion (i.e., kinematic walking measures and quantitative sensorimotor impairments), following an acute exacerbation of MS. These studies will provide important new insights into how sensorimotor impairments relate to mechanisms of locomotion as well as the role of white matter fiber tract changes during exacerbation and subsequent recovery of locomotion in people with MS.
Subjects will be tested at four time points: an initial session (for MS subjects, during an acute exacerbation), 6 weeks later, 3 months, and 6 months after the first session. During each session, subjects will undergo a clinical examination to systematically document each subject's status. In addition, we will use kinematic measures to determine how locomotion is affected by an acute exacerbation and how it changes over the time following an exacerbation of MS. Lastly, subjects will undergo an MRI in which MT and DTI techniques will be used to analyze new lesions in specific white matter tracts.