Multiple sclerosis represents a chronic inflammatory and degenerative disease of the central nervous system that leads both to demyelination and axonal loss. It is characterized by axonal myelin sheath destruction, gliosis, different grades of axonal loss and progressive neurological dysfunction. Multiple sclerosis represents the most frequent cause of chronic neurological disability in the young adult.
Multiple Sclerosis Epidemiology :
The incidence and prevalence of multiple sclerosis is higher in North America, Northern Europe, South of Africa and Australia ( 100-150/ 100,000 inhabitants) and lower in ecuatorial regions, Central Africa, Asia and Southern Europe (20-50/ 100,000 inhabitants).
Onset age is between 23 to 29 years (16-60 years) as follows:
- between 20 to 40 years in 70% of cases;
- over 50 years in 10% of cases;
- under 10 years in 0.3% of cases.
The female/ male ratio is 1.8.
Multiple Sclerosis Etiology:
The exact cause of multiple sclerosis is unknown but is suspected the contribution of environmental, genetic and immunological factors.
- Environmental factors.The nature of environmental factors is not precisely known, but multiple sclerosis has a regional incidence which has to be taken into account.
- Genetic factors. There is a genetic susceptibility with a varying prevalence according to the ethnic group ( high in Northern European Caucasians and low in East Asians). There is an association between the high frequency of the disease and certain alleles within the MHC ( major histocompatibility complex) region of chromosome 6. For Northern Europeans there is an association of multiple sclerosis with HLA-DR2 antigen.
- Immunologic factors. Arguments that plead in favor of the autoimmune pathogenesis of multiple sclerosis are represented by the fact that demyelinisation is mediated by the peripheral activation of T cells and possibly by antibodies against different myelin antigens and central nervous system. In multiple sclerosis the blood brain barrier becomes permeable and allow the passage of the activated inflammatory cells (mainly lymphocytes) in the brain. This cells will initiate an inflammatory attack on myelin mostly through macrophages and microglia, influencing the nervous conduction and causing the loss of the myelin forming olygodendrocytes. Inflammatory episodes lead to progressive neuronal loss, astrocyte overgrowth and scar forming.
According to recent immunohystological investigations on biopsied or autopsied brain fragments from multiple sclerosis patients, four possible pathological subtypes of lesions have been identified according to the inflammatory degree, myelin destruction and olygodendrocytes preservation. In all situations macrophages are ten time greater than T cells, that themselves are ten time more numerous than B cells.
The following pathological subtypes are described:
- T cell and macrophage-mediate demyelination, in 18% of cases.
- T-cell and macrophage, plus antibody-induced or complement-mediated demyelination, in 56% of cases.
- Oligodendrocyte dystrophy and apoptosis with myelin deregulation, in 24% of cases.
- Primary oligodendrocyte degeneration with features similar to viral, ischemic or toxic oligodendrocyte damage, in 2% of cases.
Multiple Sclerosis Pathophysiology:
Demyelination causes a conduction block and accounts for acute deficits characteristic of the early years of the disease. Inflammation also contributes to acute conduction block, which is clinically manifested with neuronal function loss, leading to neuronal deficits. This pathophysiological mechanisms are characteristic for the initial phase of the disease. Inflammation is followed by a recovery phase, resolution of inflammatory edema, remyelination, conduction restoration in persistently deyelinated fibers by insertion of sodium channels into internodal membrane and cortical readaptation. Irreversible deficits may be due to failure of demyelinated fibers to restore nervous conduction or due to axonal loss.
Multiple Sclerosis Symptoms:
For 90% percent of patients, the disease will evolve with symptoms in a relapsing-remitting manner. The firs clinical attack consist in focal neurological signs (unique or multiple) that typically develop over a few days, persist for several weeks and resolve spontaneously over several weeks or months. The first clinical manifestation is called clinically isolated syndrome. The most common presenting symptoms relate to lesions in the spinal cord (in 50% of cases), optic nerve (in 25% of cases) or brainstem/cerebelum (in 20% of cases).
Spinal cord onset:
- sensory symptoms such as tingling, numbness, burning, tight bands, altered temperature sensation, Lhermitte’s symptom ( the sensation of electric discharge along the spine, at neck flexion);
- motor symptoms such as weakness, paraparesis, monoparesis, tetraparesis, clumsiness;
- sphincter incontinence, constipation, impotence.
Optic nerve onset is unilateral in 90% of cases and consists in blurred vision, visual loss, reduced color perception, pain on eye movement, phosphenes or optic atrophy.
Brainstem/Cerebelum onset with symptoms such as diplopia, dysarthria, vertigo, nystagmus, facial numbness or weakness, deafness and paroxymal symptoms such as trigeminal neuralgia and tonic spasm.
Other symptoms can be represented by hemiparesis, hemianopia, dysphasia, seizures or cognitive impairment.
Multiple Sclerosis Diagnosis:
Diagnosis of multiple sclerosis consists of the clinical evolution of the disease in separate attacks and of the paraclinical findings.
Paraclinical examinations are represented by:
- increased Ig G;
- MRI examination evidence demyelination lesions in the white periventricular matter, in pons, cerebellum and cervical spine ( this are the elective zones);
- visual, auditory and sensory examination can evidence the disease.
Diagnosis of multiple sclerosis can be:
- Certain - two attacks in different sites of central nervous system that last more than 24 hours and are separated by at least one month + paraclinical confirmation.
- Probable – two attacks and one clinical evident lesion or one attack and two clinical evident lesions, confirmed by MRI examination.
- Possible – one attack and one clinical lesion confirmed by MRI.