Multiple sclerosisTHE DISEASEMultiple sclerosis (MS) is a chronic, inflammatory, neurodegenerative, autoimmune disorder of the central nervous system, in which multifocal lymphocytic infiltration causes demyelination and axonal damage.1 (MS) aects €ј2.5 million people worldwide. 2MS affect mainly young people with onset usually at the age of 20-50 and a mean age of onset of 30 year, although the disease may develop also in childhood and after the age of 60, and is 3 times more common in females than in males.3 the causes of MS thought to be due to genetics with trigger by environmental factors.
Potential environmental factors include viral infections (e.g., EBV, CMV, and herpes simplex 6), vitamin D deciency, smoking, and circadian rhythm disruption.3 Life expectancy in MS has improved over time, currently standing at almost 50 years after clinical onset for women and 40 years for men, although it is still 6 years below normal life expectancy.3 Myelin is a protective sheath of the neuronal axons produced by oligodendrocytes making the transmission of the action potentials faster along the neurons .
In MS the immune system attack and destroy this sheath resulting in a combination of heterogeneous symptoms including movements, sensations, emotions, cognition and vision as a result of the destruction to different types of neurons.THE TYPES OF MSMS can be classified into two main types : relapsing remitting MS (RRMS) and Primary progressive MS (PPMS). RRMS is clearly defined attacks of new or recurrent neurologic symptoms and signs with full or partial recovery and lack of disease progression between disease relapses. This type accounts for approximately 80-85% of initial diagnosis of MS.4 when this type become more advance it may continue with steady progression with lack of relapses and then it is called Secondary Progressive MS (SPMS). PPMS: the disease progression from onset with occasional plateaus and temporary minor improvements allowed. Approximately 10-15% of MS patients have PPMS.4 when the progression is followed by sudden attacks then continues then it is called Progressive Relapsing MS (PRMS). THE SIGN AND SYMPTOMS.The sign and symptom depend on the location of the lesion of demyelination (plaque). Plaques in the brainstem may cause dysarthria, problems with eating and swallowing . Plaque in the optic nerve may cause blurred vision or in advanced state blindness, while plaques in the nerves that control the eyes movements may cause Nystagmus (rapid, involuntary eye movement), Diplopia (double of vision) or even painful eyes movements. Damage of the motor pathway may cause Ataxia, tremor, muscles spasm or weakness. While damage of the sensory pathway may lead to paresthesias or Numbness. Moreover, plaques in the autonomic nervous system may cause bowel and bladder problems and sexual dysfunction. Symptoms may also include emotional changes like depression and anxiety and sometimes problem with cognition. Rather than Uhthoff’s phenomenon (transient ‚uctuation or worsening of MS symptoms with a rise in body temperature) and Lhermitte’s phenomenon (an abnormal electric-shock like sensation down the spine or limbs on neck ‚exion).5THE PATHOGENESIS.MS start in the periphery by the activation of CD+4 AUTOREACTIVE T HELPER CELL 1 which can recognize the CNS antigens. These cells secrete pro-inflammatory chemokines, cytokines and matrix metalloproteinases which produce several changes in the endothelial cell of the blood brain barrier making the movement of Th1 into the CNS easier. When T-cells reach the CNS they become reactivated by recognizing the antigens of the antigen presenting cells (APC), once it is reactivated it start to secrete specific cytokines that induces the migration of B-cells natural killer cells and others. When they reach the CNS the antigen antibody reaction occur and the demyelination and the injury begin . THE DIAGNOSISThe diagnosis of MS is by excluding the other neurological diseases that are similar to it, also by the sign and symptoms and their relation to the lesions in the CNS. Cerebrospinal fluid analysis is also used in the diagnosis, elevation in the number of immunoglobulin may be an indication. Magnetic Resonance Imaging (MRI) of the CNS can locate the plaque and could be used to follow the progression of the disease. To differentiate between MS and the other neurological diseases there are several approaches. The McDonald criteria, which combine these paraclinical assessments with clinical examination, are the most commonly used diagnostic approach.6 THE TREATMENTSYMPTOMATIC TREATMENTSMany types of drugs are used to treat the symptoms of MS such as : pain, muscles spasm, ataxia, fatigue, constipation, sexual dysfunction and others.This table summarize some of these symptoms and the drugs used to treat them: Disease-modifying treatmentsThese drugs are used to decrease the number of attacks or prevent the buildup of the disability. They are not a treatment for the disease but they decrease the immune response of the body by inhibiting the immune cells .The following figure show Proposed treatment algorithm after determining disease severity by magnetic resonance imaging (MRI) and clinical measures:There are currently 13 DMs that have been approved for the treatment of MS and about half of them have only become available in the past 5years.8The following table show the injectable DMTS that have been approved by the FDA: This table show the oral DMTs that have been approved by the FDA :This taple show the intravenous DMTs that have been approved by the FDA :1 -Systematic literature review and network meta-analysis of cladribine tablets versus alternative disease-modifying treatments for relapsing”remitting multiple sclerosis.- Multiple sclerosis, a treatable disease 2-file:///C:/Users/user/Desktop/MS/milo2014.pdf3 – Ocrelizumab: A New Therapeutic Paradigm for Multiple Sclerosis3 Multiple Sclerosis over the last 25 years: an introduction3 -file:///C:/Users/user/Desktop/MS/milo2014.pdf 4 – Multiple sclerosis, a treatable disease6 – file:///C:/Users/user/Desktop/MS/etm-13-06-3163.pdf7 – file:///C:/Users/user/Desktop/cross2014.pdf