Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system for which the exact cause is unknown. It is suspected that MS is a disorder of the immune system whose development is facilitated by certain genetic and environmental factors. In other words, development of the disease is facilitated in people who inherit a genetic susceptibility to MS, who live on the latitude band where MS is most prevalent and who, at a vulnerable age (early teens), come into contact with a virus or whatever antigen may trigger off the immune reaction leading ultimately to the progressive demyelination and neurological damage we call MS. The natural course of the disease is also variable and often unpredictable to start with.
At onset, approximately 85 per cent of new cases follow the relapsing remitting (RR) pattern of disease.1 This consists of acute inflammatory attacks with symptoms of inflammation and impairment according to which nerves have been targeted by the disease process on that occasion. Any white matter can be affected but optic and sensory nerves are often singled out at first. The first symptoms are therefore often optic neuritis or a tingling sensation in the legs. Symptoms usually develop over days, remain constant for a few weeks, then resolve gradually over a couple of months.
With time, remissions are less complete and some disability persists. More than 80% of the relapsing remitting group eventually move along the continuum of disease to the secondary progressive form with a gradual accrual of irreversible disability regardless of whether relapses continue or not.2
Until 1993 there was no disease-modifying treatment available for multiple sclerosis. This has enabled researchers interested in the natural history of untreated MS to amass data on large numbers of patients followed for almost 30 years. In future comparisons can be made between the time taken for disease to progress in patients treated with interferon beta from the onset of symptoms with the experience of patients who had no access to disease-modifying therapy.
Natural history data allow certain broad generalisations to be made about untreated MS:
The younger a patient is at diagnosis, the better the outcome.3
Disease manifesting first as optic neuritis or with sensory nerve symptoms has a better prognosis than disease manifesting first as a motor nerve problem.3
The more relapses a patient experiences in the first two years, the worse the prognosis in terms of rapid progression to severe disability.4
Slow progression of disease up to EDSS 3 predicts fewer years of severe disability later.
After patients reach EDSS 4 and enter the secondary progressive phase their disease progresses more rapidly and at a fairly uniform rate.
Men have a worse prognosis regarding disease severity than women.3
The median time to reach EDSS 6 (beginning of dependence on carers) is between 14 and 20 years.4, 5 For patients who suffer five or more relapses in their first two years from diagnosis, the probability of being unable to walk unaided (EDSS 6.5) within 10 years is 95%.5
Professor George Ebers of the London Health Sciences Centre, Ontario, Canada, recently presented data on 1,099 MS patients, followed for 25 years, at the 1998 meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).4 Information was still available on almost 90 per cent of the study population. Over the years, 3 per cent of participants were found not to have MS and 10 per cent were lost to follow-up.
Of the remainder 286 (30.8%) had died with 179 of those deaths (62.8%) attributed to MS. Of the others, 10% died of cancer, 3% of respiratory disease and the rest of heart disease.
The number of relapses experienced by patients during the first year after diagnosis was measured against time to reach specific points on the Kurtzke expanded disability status scale (EDSS).
Time to reach an EDSS score of 3 (mild-to-moderate disability), was:
13.2 years for patients experiencing one attack in their first year;
9.9 years for those with two relapses;
7.65 years for those with three relapses;
2 years for five or more attacks over the first two years.
Time to reach EDSS 8 (bed bound for most of the day) was:
32.78 years for those with one attack in their first year;
35 years for those with two relapses in the first year;
24 years for those with three relapses in their first year;
15 years for those with five or more attacks in the first two years.
Median time to reaching the secondary progressive stage of the disease from onset for the whole study population was:
13.9 years for EDSS 6;
24 years for EDSS 8;
51 years to EDSS 10.0 (death).
Data on more than 2,500 MS patients has been collected since 1976 by Professor Christian Confavreux of Hopital de l'Antiquaille, Lyon, France, and was also presented at the 1998 ECTRIMS meeting.5 Across the board, this study shows the following:
Median time to reach EDSS 4 from onset is 8 years;
Median time to reach EDSS 6 from onset is 20 years;
Median time to reach EDSS 7 from onset is 30 years;
Median time to reach EDSS 10 (death) from onset is 40 years.
The pivotal studies of Betaferon in relapsing remitting and secondary progressive MS give an idea of how the natural history of MS may be altered with treatment.5, 6
A patient with RRMS who might normally experience three relapses in the first year could expect to suffer only two as a result of Betaferon treatment. According to the Canadian data this would mean a patient could anticipate three extra years before reaching an EDSS score of 3 (mild disability) and 11 extra years before reaching EDSS 8, the bed-bound stage.
The earlier a patient begins therapy with interferon beta-1b, the greater the chance of suppressing disease etkinligini and preserving the integrity of nerve axons and their myelin sheaths. By maintaining the structure of the nervous system as long as possible, impairment of neurological function should be minimised.