DN2M » Multiple sclerosis

Multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) leading to demyelination and neurodegeneration. MS affects approximately 80,000 people in France, most of them being young adults with a sex ratio of female to male of 3:1. Approximately 85% of patients present with relapsing-remitting MS, characterized by acute attacks (relapses) followed by partial or full recovery (remission). Patients can manifest with a heterogeneous group of physical symptoms including changes in vision, weakness, dyscoordination, sensory loss or distortions, changes in bowel and bladder function and of non physical symptoms such as depression, fatigue and cognitive changes. The other 15% present a progressive course from the onset, with or without superimposed relapses. Progression of disease may eventually lead to severe physical and cognitive disabilities. The life expectency is decreased by approximately 10 years. Diagnosis is made according to the recent revised 2010 McDonald criteria, including clinical and paraclinical laboratory assessments emphasizing the need to demonstrate dissemination of lesions in space and time and to exclude alternative diagnoses. The criteria for diagnosing MS have been a moving target over the past few years, as more evidence accumulates about the benefits of early treatment. Paraclinical tests include mainly brain and spinal cord MRI and CSF analysis. MRI is highly sensitive to detect symptomatic and silent lesions (Figure). Studies have suggested that genetic and environmental factors, including vitamine D deficiency and smoking, may influence the development of MS. Many studies suggest also a viral etiology (such as EBV) with an infection occuring in children and adolescents. MS is a heterogeneous disease with a broad spectrum of interindividual differences in clinical presentation, location and frequency of lesions, serological abnormalities, and response to treatment. Despite some prognostic factors, decribed mainly from MRI data in large cohort, the course of the disease remains unpredictable.

Most experts agree to consider that inflammation into the CNS is the primary cause of damage. Both innate and adaptive immunities are involved. Activated T and B lymphocytes contribute and interact together at the different stages of the disease. Targets include myelin and axonal components. Other immune cells are involved, such as microglial and dendritic cells. In progressive forms, lymphoid follicles are present in subpial regions and meninges. The mechanisms leading to axonal loss are not fully understood. 

Many medications and other measures may be used to ameliorate MS symptoms. The availability of disease modifying therapies has revolutionized the care of patients with the relapsing forms of this disease. These medications help control the underlying disease process, probably by decreasing immune mediated inflammation. They do not cure the disease or reverse the damage that has occurred with prior events. In general the effects of these agents appear more potent when they are given to patients before more severe widespread damage and disability have occurred. Since the introduction of interferonβ and glatiramer acetate in the 1990s, MS has morphed from being a virtually untreatable disease to arguably the most dynamic area of new treatment methodologies and applied research in all of neurology. The second step has been made with natalizumab, a monoclonal antibody which dramatically decreases the entry of activated lymphocytes into the CNS. Recent advances include dalfampridine, improving walking capacities in some patients and fingolimod as the first oral drug for relapsing-remitting patients. In the near future, new orals and monoclonal antibodies will be probably approved for relapsing MS with specific targets such as CD52, CD25 or CD20. The therapeutic algoritm considers a difficult assessment of the benefit risk ratio. There are however many unmet needs mainly for the progressive forms.

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Figure : Typical hypersignals in the brain white matter suggestive of demyelinating lesions in a young MS female (left), one of the lesions has a gadolinium enhancement (right, red arrow)