The different forms of MS

These are people who develop a first inflammatory attack in the CNS with typical MS symptoms. However, there is no dissemination of lesions either in the cerebral space (only one lesion is detectable) or in time (there is no old inactive lesion and a new active lesion). In the absence of this dual spatial and temporal dissemination, the diagnosis of MS cannot be made, and we have to accept that the definitive diagnosis remains pending. This first isolated attack will be treated with cortisone derivatives if necessary, but regular checks will need to be carried out in the months that follow, in particular with brain imaging.

Some are people who have had a first and single attack of multiple sclerosis with MRI scans showing the presence of several lesions, some old, others recent and active (double spatial and temporal dissemination). Other patients may have had a single attack, but subsequent MRI scans have shown one or more new lesions without inducing new symptoms. Most patients have had at least two clinical attacks of the disease. This is the majority form of MS (55%), with attacks varying in frequency and intensity, either completely reversible or leaving persistent after-effects, but with no detectable worsening of symptoms between two attacks. MS attacks appear and set in within a few hours or days, but never suddenly. Symptoms must persist over 24 hours in the absence of fever. They must be accompanied by objective abnormalities on neurological examination. However, a relapse can be diagnosed retrospectively if the patient provides a reliable and typical description. This form of MS can be inactive, either spontaneously or thanks to immunomodulatory treatment ("NEDA" status, described in the chapter on "Immunomodulatory treatments"), or active, if clinical relapses occur and/or if MRI scans show new lesions compared with previous imaging. The frequency of relapses decreases spontaneously over the course of the disease (-17% per 5-year period), but with age, the symptoms they cause become less reversible.

This is a progressive disability due to neurological deficits over several months, either from the start of the disease in the absence of any initial relapse (primary progressive form, which accounts for 10 to 15% of MS cases), or after an initial phase of relapses and remissions (secondary progressive form). We do not yet have specific, precise criteria for determining the moment of transition from a form with relapses and remissions to a secondary progressive form. However, studies have shown that if the total number of lesions observed on MRI scans was high 5 years after the onset of the disease, the risk of developing into a secondary progressive form was very high. This progression must be assessed at least once a year on the basis of a disability scale from 0 to 10, called EDSS ("Expanded Disability Status Scale"). This scale is based on the neurological examination and the walking perimeter. It may be supplemented by a measurement of walking speed over 25 feet (7.6 metres), a manual dexterity test (Nine Hole Peg Test or NHPT) and cognitive tests (in particular the Symbol Digit Modalities Test or SDMT). Progression must be distinguished from the accumulation of deficits resulting from the after-effects of previous relapses. In these primary or secondary progressive forms, 4 subtypes can be distinguished: 1° Active forms with progression, 2° Active forms without progression, 3° Non-active forms with progression, and 4° Non-active forms without progression (in this case, the disease is stabilised "at a plateau" but could still progress later). The term "active" refers to the presence of relapses added to the progression and/or changes in MRI scans (new lesions or increase in volume of pre-existing lesions). The term "progression" refers to an increased disability measured by the EDSS and the additional tests described above.

It must be stressed that the severity and activity of the disease can change significantly but unpredictably throughout its course. The term "benign" MS is always a retrospective diagnosis, which can only be made after 20 or 30 years of evolution.

Finally, it should be noted that the distinction between "forms with relapses and remission or remittance" and "secondarily progressive forms" is open to question and has been challenged by detailed clinical studies, particularly of placebo groups in clinical trials. Progression independent of the occurrence of relapses designated by the acronym PIRA ("Progression Independent of Relapse Activity") may occur even in what are known as remittent forms. This is because axonal transections and degeneration during an acute attack appear much later than during the attack, and the progressive, centrifugal increase in active chronic lesions occurs quietly and insidiously.

Somewhat arbitrarily, late-onset forms of MS begin at the age of 50 or older, and juvenile forms begin before the age of 18. Overall, according to the Swedish national register, juvenile-onset forms account for 5% of all MS patients, adult-onset forms for 84% (with an average age of onset most often between 30 and 32 years), and late-onset forms starting after the age of 50 account for 11% of MS patients.

Late-onset forms are predominantly (75%) relapsing-remitting MS, but in 25% of cases they are primary progressive forms, whereas these are seen in only 4.5% of adult-onset forms. In these primary progressive forms, there is no female preponderance and men are affected as much as women by the disease. This will most often be lower limb involvement with progressive disturbance of walking and limitation of the walking perimeter. Although it starts later, this primary progressive form has a poorer overall prognosis, given the progressive loss of walking independence. It is due to the presence of plaques in the spinal cord causing focal or extensive atrophy. There are also progressive cerebellar forms which cause increasingly severe tremors and balance problems to the point where walking becomes impossible without loss of strength in the lower limbs. So instability is the dominant factor. There are also rarer progressive cognitive forms, in which intellectual problems progressively worsen while physical deficits are minimal or even absent.

Juvenile forms beginning before the age of 18 are almost always relapsing-remitting MS and therefore never primary progressive forms. They are characterised by a clear female predominance (75% of cases occur in women) and by relapses that are often more frequent than in adults. As these forms appear at an age when the brain is still maturing, there will be more rapid interference with intellectual capacities, learning mechanisms and memory, and school results may be affected. Juvenile forms do not develop more rapidly than adult forms, but as they begin earlier, significant disabilities can be observed around ten years earlier. There is currently a consensus that these juvenile forms should be treated early and vigorously, given their possible impact on brain maturation. These juvenile forms usually begin after puberty, between the ages of 14 and 18, but some can start as early as the age of 10.