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New Treatments for Multiple Sclerosis and Demyelinating Diseases

Multiple sclerosis is a condition characterized by inflammation and damage to the myelin sheath. The axons are also damaged in multiple sclorosis. We estimate now that about 400,000 patients have MS in the U.S. and at least 60:100,000 in the United States. It’s the third most common cause of severe disability between 15 and 60, and only trauma and rheumatologic disorders are ahead. Henry McFarland in the NIH group estimates that we are diagnosing correctly 100 to 200 new cases.

Demyelination could be direct action of the cytokines on myelin or on the oligos. Could be the stimulation from beta cells to produce antibodies against oligos, or direct attack on myelin by activated macrophages. It’s a very complicated sequence, but interestingly, we did some work on Betaseron and Avonex, the other interferon also works this way.

Schumaker criteria from the NIH in 1965. To have objective abnormalities, history and examine, involves two or more parts of the CNS. It primarily reflects white matter involvement, ie, long tracts, and one of two patterns: two or more episodes. Each lasting 24 hours or more and a month or more apart, with relapsing or remitting or exacerbating.

The criteria modified by the Poser committee in 1985, and that was the advent of MRI, and this is the key thing here. Objectively, one lesion on your examination plus MRI with white matter lesions that can’t explain the exam lesions. So in other words, if you were to have somebody with cerebellar symptoms and have one lesion in the cerebellum and nothing else on the MRI.

Now we also have other classifications in addition. Definite MS: that’s somebody who fulfills all the criteria. Probable, and possible. Probable means that the fixed deficit is slight, history suggests multiple remissions and exacerbations but only one site in the CNS has been involved, or in the MRI, only one lesion is seen. Almost always this will turn out to be MS. Possible is when a lesion is progressive, involving only one site, but other sites have been excluded.

Treatment. Treating the acute attack, treating symptoms, preventing exacerbations. The acute attack, after the optic neuritis study, most centers now use 3-5 days of IV Solu-Medrol, methylprednisolone, and no taper. But some centers still use a taper. But the reason for not using it is, in the optic neuritis study, the patients who got oral prednisone had an increased number of exacerbations compared to those who were on placebo. Similarly, some people still sometimes favor oral steroids rather than IV. Symptom treatment, the key thing to remember is that this has been a huge advance in treating symptoms.

Preventing exacerbations: we have the ABCs and starting out first with Betaseron, beta interferon Ib. Then next after quite a bit of time came Avonex, or beta interferon Ia, and finally Copaxone, although actually Copaxone was the first drug that was used back in the early 1980s, which is glatiramer acetate.

The major side effects with the interferons are flu-like symptoms after the injection and headache. In Betaseron injection site reactions, particularly a red little area where the injection was made, and rarely necrosis there. In the first Betaseron study for relapsing remitting MS, depression was a feature in some patients. They actually had five suicide attempts, one successful.

Preventing progression: these are primarily other immune altering drugs. These are primarily borrowed from the cancer spectrum: azathioprine, cyclophosphamide, combinations with steroids and methotrexate.

SSPE is caused by a persistent measles infection. Much less commonly seen with the measles vaccine, the live measles vaccine, but it can. It’s really rare and is reminiscent in many ways to Creutzfeldt-Jakob and we really don’t have a treatment and here’s the problem. We are seeing it in AIDS patients and that’s where we are seeing it most commonly. There are some cases, by the way, of PML that have no apparent antecedent neoplastic disorder, AIDS.