From the first clinical signs to confirmatory MRIs, how is multiple sclerosis diagnosed? Dr David Laplaud, neurologist specializing in MS at Nantes University Hospital, answers us.
Why Doctor: Is the diagnosis of multiple sclerosis difficult to establish?
Dr David Laplaud: It was 30 years ago, but since magnetic resonance imaging (MRI), MS is not very difficult to diagnose. The question is rather: when should we think about looking for MS? Identifying the disease can be complicated for patients or general practitioners who are not specialized and who will not always take into account the patient’s signs and complaints, and therefore not prescribe the tests which will lead to the diagnosis. Hence the risk, sometimes, of a diagnostic delay. But when we do MRI exams to specifically look for MS, we find it.
Generally speaking, it is isolated sensory disorders that cause the most errors and delays in the diagnosis of MS.
What are the warning signs of MS?
The most common signs are sensory disturbances: tingling, pain, burning sensations or numbness, particularly in the legs. It occurs in relatively young people: cases begin at 13-14 years old, then they increase in frequency with a peak at the age of 30, before decreasing as they age. Certain circumstances seem to increase the frequency of signs, such as postpartum. Many patients I interviewed to make the diagnosis say that they had felt symptoms before, such as tingling, but that they eventually passed. However, with hindsight, we can assume that these symptoms were the first of MS… Generally speaking, it is isolated sensory disorders that cause the most errors and delays in diagnosis.
Next in order of frequency are visual disturbances, caused by retrobulbar optic neuritis, an inflammation of the optic nerve. This poses few diagnostic problems because, in principle, the ophthalmologist will think of MS and refer the patient to a neurologist. Just like other symptoms, such as balance or urinary disorders, which lead to explorations and therefore to diagnosis of the disease.
Criteria, examinations… How is MS currently diagnosed?
The first “modern” criteria, which date back to 1997, are essentially based on clinical signs and MRI examinations: in patients who have had an acute episode of damage to the central nervous system, imaging will highlight lesions cerebral. There are two types of criteria which will allow us to say whether these lesions are those of MS:
– The criteria for spatial dissemination: this inflammation of the central nervous system must reach different structures in the brain or in the spinal cord;
– The criteria for temporal dissemination: it must be a dynamic process over time, and not a single episode of neuroinflammation. We can detect if it is progressive by doing other MRIs at other times (to see if new lesions have appeared between exams) or by doing a lumbar puncture. When both dissemination criteria are met, the diagnosis of MS is made.
The latest criteria, which date from 2017, make it possible to diagnose with greater sensitivity and very early, from the first manifestation of the disease. Today we can even go further and predict the diagnosis in patients who do not yet have MS. For example, in a patient who complains of recurrent headaches, the MRI may show lesions typical of MS. We do not then speak of MS, because there is no clinical inflammatory attack (sensory, visual disturbance, etc.), but the simple fact of coming across these lesions indicates to us that the patient is very likely at risk of developing a MS in the coming years. This is crucial at the very beginning of the disease because, once we know that a person is at risk, we can quickly implement treatment.
If current treatments prove to be very effective for the relapsing form of MS, they are not at all, or very little, for progressive forms.
In what forms can MS develop?
There are three types of MS. The “relapsing-remitting” form, which begins between the ages of 20 and 40 and progresses in flare-ups, affects 90% of patients, including three women for every man. More serious, the “primarily progressive” form represents 10% of cases and affects older people, from the age of forty. Finally, MS can be relapsing initially and evolve, after 15-20 years, towards a “secondarily progressive” form: there are no more relapses but a disability appears, often motor. Obviously, the prognosis is not the same for the relapsing form as for the progressive forms: if current treatments prove very effective for the first, they are not at all, or very little, for the others. That said, if we prevent the relapsing form from evolving, we prevent the secondarily progressive form from occurring. Hence the interest in treating early.
The earlier the diagnosis is made, the more effective the treatments?
These are curative treatments, in the sense that they will prevent the occurrence of clinical events and the appearance of new lesions in the brain and spinal cord, and therefore prevent the central nervous system from becoming further damaged. Therefore, the earlier treatment is administered, the more likely it will be effective. However, we must remember that we are not currently capable of repairing the lesions: from the moment there are clinical signs present, it is not possible to go back. Everything that is lost is lost, hence the importance of not losing!
The patient’s prognosis, in terms of disability, also depends on each individual’s own ability to repair their brain damage, at least partially.
According to the Brain Institute, “the progression and time taken for the onset of irreversible disability also vary depending on the ability of each affected person to ‘repair’ their brain damage”. Can you explain ?
It is for this reason in particular that MS is considered to be a very heterogeneous disease. When we autopsy the brains of patients who have been affected, we observe that lesions have remyelinated in some, but not in others, or very little. The patient’s prognosis, in terms of disability, therefore also depends on each individual’s own abilities to repair their lesions, at least partially. I followed a patient whose MS began in the late 1980s and who ultimately lived a completely normal life for forty years without any treatment. It was only recently that he came back to see me, because the discomfort in his leg returned. Conversely, I am a woman, who has suffered from MS for around ten years, who was immediately treated but who today suffers from difficulties in walking, in working… Why are there such disparities between patients? Maybe there are different repair abilities, or maybe there are diseases with distinct inflammations or degrees of inflammation.
So are there as many MS as there are MS patients?
Many factors for poor or good prognoses still make it possible to stratify patients and to select this or that treatment according to their profiles. In some patients, it is possible to predict from the first clinical event that MS is likely to progress very quickly. We will therefore administer a very powerful treatment to control the disease. In other patients, who have few lesions and recover well, we will settle for a less powerful treatment.
Do we know why women are more affected than men?
Not really. There is the possibility of female hormones, which could play a role in the immune system, but this is a deduction made from work on animals. We don’t know how this works in practice, and why women are more at risk. That said, in most autoimmune diseases, the sex ratio is to their disadvantage… Some even affect women almost exclusively.
