Treatment of Multiple Sclerosis

Treatment issues in MS generally fall into four categories. These are (1) symptomatic treatment; (2) treatment of acute MS exacerbations; (3) reducing the risk (“prevention”) of future exacerbations and, more importantly, reducing the risk of sustained increases in disability; and (4) neurological rehabilitation. In recent years there have been advances in each of these four areas.

In the past, treatment of MS was limited to empirical management of symptoms,

i.e., symptomatic treatment. Most treatments were untested and were of questionable value, at best. Interested readers are referred to the Diary of Augustus D’Este where descriptions of treatments employed are recounted [3]. Treatments were really generic, ineffective, and sometimes dangerous remedies such as cathartics, enemas, and bloodletting. Many ineffective empirical treatments continue to be offered by misguided individuals and quacks.

Symptomatic Treatment

Symptomatic treatment covers many areas, but only a few specific issues will be dealt with in this review. Fatigue, spasticity, and bladder symptoms are among the most important areas. Also important is the management of the paroxysmal disorders: paroxysmal dystonia, paroxysmal akinesia, paroxysmal dysarthria, trigeminal neuralgia, facial myokymia, and hemifacial spasm. Treatment can be dramatically effective.

Fatigue is a prominent complaint in the majority of patients. In reality, the fatigue of which patients complain is predominantly fatigability, although the occasional patients with severe exacerbations may awaken with overwhelming fatigue. The first drug for fatigue to be evaluated in double-blind trials (and shown to effective) was amantadine HCl (Symmetrel®) [164]. A dose of 100 mg twice daily is an effective antiviral, initially virtually preventing all influenza type A infections and 90% of type B infections and a lower but important risk reduction for other paramyxovirus infections. The sustained reduction of fatigue observed in the majority of patients is presumably due to its weak dopamine agonist properties, rather than an antiviral effect. In addition, a variety of adrenergic drugs have been used to treat fatigue, but tolerance tends to develop quickly and habituation is also problem [165]. Modafinil (Provigil®), a more selective member of this family of drugs appears safe and tolerated in small (200 mg) daily doses [166]. Unfortunately, in our experience, tolerance seems to develop quickly too. A matter of concern is that in vitro adrenergic drugs appear to promote cellular immune mechanisms, calling into question their use in fatigue management. Fatigue and depression commonly coexist, and fluoxetine (Prozac®) is commonly used to manage these patients. Interestingly, fluoxetine has immunomodulatory properties, with resultant increases in the Th2 lymphokines, IL-4, and TGFp [167]. Fatigue lessens in patients who stabilize clinically, spontaneously, or in conjunction with immunomodulatory therapy.

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