Aggressive Treatment of Inflammatory MS Recommended
by Ann Crickmer, MSW
Doctors recommend treatment with the ABCR drugs (Avonex, Betaseron, Copaxone, Rebif) as soon as a diagnosis of MS has been made because Inflammatory MS is treatable. New diagnostic criteria reduce the number of symptom relapses necessary for a definite diagnosis, and prescribe treatment at the first MRI evidence of disease. Based on information about the first relapse, there is now predictive data about the risk for progression while on standard ABCR treatment which will determine how aggressively your neurologist will treat your disease. Various combination therapies are currently used to support the ABCRs. Their reasoning is supported by new technology in MRI research which shows that by the time external symptoms appear some brain tissue has already been destroyed. The images below reveal the increase in (black) vascular area in the brain caused by the decrease of brain tissue.
A) Normal, healthy control subject
B) Disease duration of 2 yrs Relapsing-Remitting
C) Disease duration of 19 yrs Secondary-Progressive MS
Fig.6 Trapp, Ransohoff, Fisher and Rudick." Axonal Degeneration in MS", The Neuroscientist: Jan. 1999, p. 54. Reproduced for educational purposes only.
The chart below the brain images contrasts a broader understanding of the neurological progression of MS with what we could previously only observe from external symptoms or MRI evidence of demyelinating lesions.
The dashed line on the top of the chart shows that destruction of neural tissue begins during a symptom-free Preclinical stage of the disease (heavy flat line), in spite of minimal demyelinization (arrows on bottom line). Demyelinization is not the only casualty of MS. Yes, MS causes demyelinization within plaques in the brain, but it also causes axonal damage within normal-appearing white matter outside of the demyelinating lesions. Untreated, axonal damage can result in brain volume loss of as much as .5% - 1% per year.
Even when external symptoms have "remitted" during the Relapsing stage (solid line), the arrows on the bottom line show that MS is a continually active degenerative neuronal disease in 100% functional individuals. MRI inflammatory activity is 5-10 times more frequent than symptomatic expression.
The sharpest decrease of neural tissue (top dashed line), and resulting increase in accumulating symptom impairment with no return to a Preclinical symptom-free state (heavy line), occurs at the Secondary-Progressive stage.
Now that Relapsing MS is considered a treatable disease, the primary goal for neurologists is zero tolerance of inflammation. For those whose MRI shows evidence that they are biologically not responding to the ABCR standard treatment, neurologists are now prescribing various combination drugs to stabilize the disease. Novantrone (mitoxantrone), pulse Solu-Medrol, oral Methotrexate and various dosing options for the interferons are all options with good research evidence to support them. Aggressive treatment of inflammation is important because we do not yet know the mechanism of axon loss, and cannot modify this aspect of the disease. The natural history of untreated disease is that, over the course of a lifetime, 80-90% will progress beyond the currently treatable form of MS. Before the ABCRN drugs, the MS statistical probabilities for diagnostic categories were as follows (remember that probabilities apply only to populations of people, are not predictive for any one individual, but are useful for planning and decision-making):
Of 100 people initially diagnosed with MS:
85 people are diagnosed as Relapsing:
50 will exceed a threshold of axonal loss within 10 years, and enter an irreversible Secondary Progressive form of the disease, which no longer features active tissue inflammation (demyelination)
25 will stop having active inflammation by 20 years.
10 will remain neurologically functional 20-30 years after diagnosis and are thus classified as having Benign MS
15 are diagnosed with several different types of Primary-Progressive MS; and do not return to a symptom-free baseline, although the rate of progression varies. A rare 3% in this category have a life-threatening form of MS leading to total disability in only a few years. The female-male ratio is 1:1 for PPMS. This form is thought to be biologically different than Relapsing MS.
We want to increase the percentage of those who remain at the Remitting stage for as long as possible. The ABCRNs are currently being prescribed for Secondary-Progressive MS as well because research studies have shown positive results.
To see a video interview on early treatment of MS with MS specialists Frederick Munschauer, MD and Heidi Crayton, MD, click here: http://www.healthology.com/multiple-sclerosis/video3857.htm.
References include recent presentations by Patricia Coyle, MD, George Kraft, MD, Craig Smith and Richard Rudic, MD; recent articles by Lawrence Jacobs, MD in Neurology, Stephen Waxman, MD in Archives of Neurology, Trapp, et al. in The Neuroscientist and New England Journal of Medicine, Jack Simon, MD in Journal of Neuroimmunology and Neurology and R. Rudick, MD in Neurology, amongst others. The definitions of parts of the brain came from "A Glossary for Science" from The Humanizing Brain by James B. Ashbrook and Carol R. Albright, 1997.
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