Commentary by Jacqueline Friedman, MD, Clinical Associate Professor of Neurology, Director, New York Region Veterans Administration Multiple Sclerosis Center of Excellence
Multiple sclerosis (MS), a chronic disease of the central nervous system, is thought to be initiated by an inflammatory phase followed by degeneration of both white and grey matter. While there is no cure, great strides have been made in the past ten years—we now believe that the earlier a diagnosis is suspected and treatment is initiated, the better the long-term course of the disease, even if treatment is initiated before a definitive diagnosis is made.
Treatments are divided into two categories: symptomatic and disease-modifying. Though they have been used for decades, there has been recent progress in symptomatic treatments. For example, if spasticity is not relieved with oral muscle relaxants, options now include the use of botulinum toxin injected into muscles or the use of an implantable baclofen pump to deliver the muscle relaxant directly into the spinal fluid. The pump permits significantly lower doses to be administered and eliminates systemic side effects. Fatigue, a symptom that affects 2/3 of MS patients, has been treated mainly with amantadine, a dopamine agonist. Recent clinical studies and practice have involved the use of modafinil, a drug initially developed to treat narcolepsy, to help relieve daily fatigue in MS patients, thereby potentially improving their quality of life.
MS care has been revolutionized in the last decade by the use of disease-modifying agents, which are immunomodulators targeted to alter the natural history of the disease. The two primary agents in this category are beta interferon (Betaseron, Avonex) and glatiramer acetate (Copaxone). They have been shown to decrease MS exacerbations or attacks by a third when compared to placebo, though their mechanism of action is not well defined. Disease-modifying agents may work by stabilizing the blood-brain barrier, as well as by altering the profile of the immune system from helper to suppressor function. Their more significant effect is evident on magnetic resonance imaging–a decrease in the number and size of MS lesions in the brain and a decrease in the number of lesions enhancing with dye injections, which can be a sign of active, recent inflammation. It has been shown that these modifiers decrease the amount of tissue loss and atrophy that develop in the brain, which are perhaps the most significant signs of worsening of disease and markers for cognitive decline as well. Unfortunately, these medications are expensive ($12,000/year), must be given by weekly injection and can cause flu-like symptoms and depression. If the patient is carefully followed and treated, the overall benefits may be worth the first few months of discomfort.
The most recent advance in immunomodulators is the recently FDA-approved natalizumab (Tysabri) which stabilizes the blood-brain barrier by blocking adhesion molecules. This drug has caused much excitement, especially because it can be used as a monthly treatment. Moreover, it has twice the efficacy than the interferons as evident on MRI scans. Unfortunately, three cases of potentially fatal progressive multifocal leukoencephalopathy (JC virus) have emerged in patients treated with this medication. Therefore, while still available for use, it is reserved for patients who are part of a national registry and who have failed all of the other treatments.
Though it is usually not as severe as gray matter dementia, MS has been increasingly recognized as a disease which can cause alterations in memory and cognition, and treatment modalities for the cognitive changes in MS are also being investigated. Recent early clinical studies suggest that donepezil (Aricept), mainly used in Alzheimer’s disease, may prove useful in improving cognition in MS patients; modafinil is being investigated for this purpose as well.
In addition, immunosuppressants such as mitoxantrone (Novantrone) or cyclophosphamide can be considered for use in severely affected patients, although these drugs may also have potentially significant side effects. Nonetheless, all of these agents have given neurologists new options for the treatment of MS and they have changed the way patients now approach the prognosis of their disease.
A recommended MS Review: Noseworthy et al. NEJM 343 (no.13) ,938-952 (9/28/2000)
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