Multiple Sclerosis
Multiple sclerosis (MS) is the most frequent chronic neurodegenerative disease with inflammatory, dysimmune and demyelinating aspects appearing and progressing in the central nervous system of young patients.
MS shears the same paradigm than the inflammatory diseases of other organs appearing in subject with genetic susceptibility associated with environment factors such as deficit of vitamins D, tobacco consumption or the Hygiene hypothesis. MS is a cumulative disease for inflammatory lesions and associated neurodegeneration, induced or not. Inflammatory lesions are disseminated in space (brain, spinal cord, optical nerves) and time. Those lesions are associated with diffuse and progressive tissue damage (neurons, myelin, microglia), inducing neurodegeneration and residual disabilities.
Multiple Sclerosis is found in countries with high social economical level and shows an incidence gradient «South-North”. MS exhibits an adverse sex ratio for women and it onset is from 20 years to 40 years. A pediatric onset is however found in 5% of patient before the age of 18 years. Prevalence is variable: 40 to 90 patients for 100,000 habitants in Italy but more than 200 for 100,000 habitants in the Shetland Islands (UK). In France, over 100,000 patients are suffering from MS.
There are two clinical phenotypes of multiple sclerosis. In more than 80% of patients, MS is a disease progressing by spurs of neurologic deficiency symptoms which appear for some days or some weeks and spontaneously regress partially or completely.
Neurologic disorders can be visual deficiencies (uni or bilateral retrobulbar optic neuritis), gait and equilibrium disorders, bladder and sphincter disorders, sensorial disorders; all symptoms can be present together. This is the Relapsing-remitting form of MS (RRMS). The classic progression of MS show that half of RRMS patients evolve after 15 years into a secondary progressive form of MS with less spurs but with insidious worsening and accumulation of the physical and cognitive symptoms
If symptoms are sometime regressive at least at the start of the spurs, the lesions are cumulative and induce scar tissues and neuron losses, leading to cumulative physical and cognitive impairments.
In 20% of patients, the disease progress more insidiously leading usually to a delay of diagnosis as the gait, equilibrium and cognitive disorders are slowly progressive without spurs. This form is called primary progressive MS (PPMS) and appears later on during life with a sex ratio close to 1.
It is important to state that both RRMS and PPMS are not significantly different in their immunological and histopathological characteristics.
MRI imaging is nowadays at the basis of diagnosis and therapeutic strategies of MS. MRI is the tool pointing out the silent accumulation of MS lesions. In addition of assessment of MS spatial dissemination in the nervous system, MRI allows to predict the clinical progression and therefore the temporal dissemination of MS, even if the patient has only experimented only one MS spur.
MS can be defined as soon as the first spur. This early diagnosis allows an early treatment modifying the overall disease progression. Those treatments are able to control the inflammatory process (spur), to control the building-up of inflammatory lesions by MRI, to decrease the brain atrophy and to control the disabilities accumulation.
Therapeutic progresses have been major and dynamic since the 1990’s with today, a rich arsenal of immunoactive drugs aiming mainly the inflammatory process. Immunological mechanisms thoroughly investigated but not yet fully understood, have been the basis for new molecules mostly immunosuppressive. Suchimmunoactive therapies are limited by the strict monitoring of patients submitted to long term immunosuppression and therefore prone to dysimmune side-effects such as infections.
Even if they allow a better control of the MS pathology, those drugs are not curative. It would be interesting to understand why such immunoactive drugs have been mostly efficient in the relapsing-remitting form of MS. Recently however, a dual therapy targeting the type B lymphocytes, have been found to be effective in primary progressive MS allowing a limited but significant control over the disabilities’ accumulation. It is anyway the first treatment effective against this PPMS form strengthening the hypothesis of entanglement between the focalized and diffuse inflammatory processes and the neurodegeneration.
This chronic, progressive and neurologic pathology, starting in young subject, is the second cause of disabilities after road traffic traumatism in this category of patient. Disabilities can be physical, sensorial and cognitive interfering strongly on the patient social-economical, professional and familial life. A 7 years reduction of patient life expectancy is observed after 20 years of progression compared to the general population. The stake is to diagnose very early the disease and to propose quickly treatments allowing significant modifications of the disease progression. Treatments can be modified depending on the disease progression and aggressiveness.
