Introduction

Mindy L. Aisen, MD

Director

VA Rehabilitation Research and Development Service

Multiple Sclerosis (MS) is diagnosed in one in every 2,000 people in the U.S. and remains one of the most complex and difficult neurological disorders to treat. Nearly 23,000 veterans have MS, and 10,000 sought care from the Veterans Health Care System last year. Fortunately, relative peacetime has brought about a decline in the number of veterans requiring intensive rehabilitation for new spinal cord injury. However, MS, a progressive disease which can produce similar complications stemming from spinal cord dysfunction, is not showing the same decline in the veteran population.

Much of the research funded by the VA Rehabilitation Research Service focuses on problems associated with spinal cord injury, gait impairment, visual impairment, swallowing and speech disorders, and hearing loss, all of which is directly relevant to the symptoms associated with MS. In addition, VA has sponsored some of the leading researchers in immunology and pharmacology. With this combined expertise, VA is poised uniquely to bring new knowledge to the understanding and treatment of MS.

To serve as a catalyst for novel collaborative ideas, a symposium entitled MS: A Step Forward, convened clinicians and researchers to generate a research agenda in MS for the VA. Sponsored by Eastern Paralyzed Veterans of America, National Multiple Sclerosis Society, Paralyzed Veterans of America, and VA Research and Development Office, the meeting brought together neurologists, physiatrists, engineers, nurses, health service researchers, and others to address this important clinical area. Conference leaders focused in four areas: Opportunities for clinical research and optimizing clinical services; databases and outcome assessment instruments; the current state of immunotherapy; and managing medical complications of MS.

At the meeting, VA's established national databases on spinal cord injury (SCI) and low vision, both of which contain data and employ methodologies applicable to MS were discussed. Dr. Timothy Vollmer, of Yale Medical School reviewed VA's participation in the North American Research Consortium on Multiple Sclerosis (NARCOMS) registry. Dr. Vollmer joined staff of the West Haven VA Medical Center in July of 1999. There is optimism about future clinical trials and the VA medical centers nationally are actively collaborating with the NARCOMS project to identify eligible and interested candidates for clinical studies.

Symposium participants agreed that coordination among databases would lead to better potential for therapeutic outcome studies. Within VA, there is the possibility of building on the VA's clinical computer registry for longitudinal studies. Such studies would benefit diagnostic, pharmaceutical and rehabilitative facets of care.

The diagnosis of MS is often problematic, with symptom severity ranging from mild tingling sensations to severe paralysis; the disease often takes years to clearly manifest itself. Treatment possibilities are equally diverse. They include pharmacological approaches to slow the progression of the disease and rehabilitation strategies to maximize functionality in spite of the disease. Corticosteroids have some value in reducing inflammation and ameliorating severity of acute attacks. Recently interferon compounds that help regulate the immune system have been found to be about 30% effective in controlling disease progression, but they, like steroids, have limited efficacy and may be attended by adverse effects.

The cure remains elusive, and clinical trials of new treatments are necessary. All new medications face specific four-phase human trials mandated by the FDA, and this is an area where VA and veterans can both contribute and benefit. VA has a solid track record in conducting coordinated multicenter clinical trials of therapeutic interventions and participating veterans often receive cutting edge care in the process.

VA Medical Research Service supports investigators conducting basic immunology and clinical trials of novel MS therapies. Dr. Arthur Vandenburk and colleagues, at the Portland VA are examining the role of the immune system in the pathogenesis of MS. The group includes basic scientists who study an animal model of MS, experimental autoimmune encephalitis (EAE), clinical scientists who study immune responses in MS patients, and clinicians who evaluate and treat MS patients. Specific projects include characterizing myelin attacking T cells in EAE, to develop clinical treatments for inhibiting them. This could lead to novel therapies for controlling disease activity more effectively and with fewer adverse effects than currently available agents afford.

Rehabilitation medicine seeks to optimize function through compensatory strategies. For the first time, advances in neuroscience make it possible to reach beyond this goal, to strive for genuine restoration of function. In May of 1999, an application to establish a VA Rehabilitation Research and Development Center of Excellence, focused on restorative function in MS and Spinal Cord Injury, successfully competed for funding. Directors Stephen Waxman MD and Jeffrey Kocsis PhD, of the West Haven VA, have successfully developed cell harvesting and cryopreservation techniques that will further research on transplantation of myelin-forming cells. The center will conduct clinical research related to new treatments for surgical and pharmacological neural repair, while at the same time focusing on means to provide restoration of function through rehabilitation treatments.

In parallel with treatment to control disease activity and repair damaged tissue, rehabilitation strategies are necessary to maximize functionality and quality of life. These include cognitive programs for the person with MS related memory impairment, therapies to restore motor function and help control spasticity and neuropathic pain, assistive devices to overcome difficulties in activities of daily living (ADL), and physical training approaches that take into account the temperature sensitivity common in MS. The benefits or optimal application of these strategies remains unproven and, therefore, varies among care facilities.

One of the synergies evolving from the symposium lay in the encounter with researchers from other areas. A low-vision researcher may, for instance, deal with MS patients whose visual acuity is normal, but who nonetheless describes trouble seeing. An audiologist may see those who pass pure-tone tests, but nonetheless report difficulty hearing. Their sharing these findings is a gratifying experience for both: the patient's problem lies in processing sensory information, not only in acquiring it. This sort of insight opens up the possibility of the right diagnostic questions being asked clinically, and, ultimately, the discovery of new solutions.

Other traditional areas of RR&D research include development of functional electrical stimulation applications and robotics, all approaches that may improve the function and independence of MS patients. FES represents an area of great research opportunity; long studied as a method for activating paralyzed muscles in spinal cord injury and stroke patients, its application in MS therapies appear a natural next step for the technology.

In addition, the RR&D service has been a leader in clinical research into conditions secondary to nervous system damage, such as speech disorders, bowel and bladder dysfunction, osteoporosis, and wound healing.

It has established new centers collaborating in outcome measures research in the areas of audiology, vision, and dysphagia—all important areas for veterans with MS. Many clinical disciplines must be included in the effort to control MS if it is to succeed.

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