MS affects women twice more than men and arises most commonly between the ages of 20 to 40. Caucasians are most susceptible to develop MS than other ethnicities.

The cause and the mechanism of MS are not well-understood. It is known to be a multifactorial disorder that occurs due to a combination of genetic predisposition, environmental exposures, and immune-mediated abnormal processes.

The symptoms of MS are present due to damage to the brain and the spinal cord. The blood-brain barrier is a protective layer that separates the spine and the brain from the circulating blood. At the early stages of MS, the blood-brain barrier is disrupted which allows immune cells to enter the brain. In MS, the body’s natural defense becomes abnormally primed to attack the brain and the spine and causes local inflammation. Inflammation is the primary cause of damage in MS. The trigger to this inflammation is not known. However, evidence suggests that it might be initiated by a combination of genetic predisposition and environmental exposures.

The brain and the spine are primarily made of nerve cells or neurons. Neurons have a specialized structure that enables them to conduct nerve impulses in the form of electrical signals. A neuron is made up of different components. An axon is the part of a neuron that conducts the electrical message to another neuron. Axons are covered by a fatty-protein coat called the myelin sheath. Oligodendrocytes are cells that produce myelin in the brain and the spinal cord.

Inflammation leads to the release of toxic substances that destruct the myelin sheath in a process called demyelination which is the major hallmark of MS. As MS progresses, inflammation damages the underlying axons. As a result of demyelination and axonal damage, nerve impulses cannot be properly conducted, leading to neurological deficits.

MS is believed to be associated with genetic factors because family members of individuals affected by MS have a higher risk of developing MS. Human leukocyte antigen DR beta 1 (HLA-DRB1) is a gene that encodes an important protein in the immune system and is most strongly associated with MS. Other identified genes include the interleukin-2 receptor alpha gene (IL2RA) and interleukin-7 receptor alpha gene (IL74). Both of these genes encode proteins that are involved in the activity of the immune system.

Environmental factors include exposure to certain viruses such as the Epstein Barr virus, the cause of an infectious disease called mononucleosis. Furthermore, smoking, vitamin D deficiency, and exposure to UV radiation are also associated with the onset of MS.

Since MS can damage any part of the brain or the spine, the symptoms vary between individuals. The most common symptoms are weakness, numbness, or pins and needles in one or more limbs, inflammation of the optic nerve (optic neuritis) and complete or partial loss of vision in one eye, presence of tremor or unsteady, staggering movement (ataxic gait), double vision, difficulty producing speech, dizziness, and fatigue.

Approximately, one-third of affected individuals experience continuous contraction (spasticity) in some of their muscles, mostly in legs. A common presentation is numbness in one leg that spreads to the other leg and eventually to the pelvis, abdomen, and chest. Most individuals affected by MS experience bladder dysfunction which may lead to incontinence in some.

Different MS subtypes may have different manifestations as well.

Relapsing-remitting MS is associated with visual impairment, numbness or tingling, fatigue, spasticity, and learning and memory impairment. These symptoms are experienced during relapses which develop over hours to days. Relapse episodes often reach a plateau for several weeks and then begin to improve. During the early stages of MS, symptoms recover completely during remission. However, as the disease progresses, some abnormalities from relapses continue to persist during remission.

Typically, relapsing-remitting MS develops into secondary progressive MS. There is no clear transition from one subtype to another. The flare-ups in relapsing-remitting MS gradually begin less suddenly and persist more chronically. As remissions become less complete, the flare-ups become less dominant and well-defined and the progressive form of MS dominates. Affected individuals may also experience psychological impairment and increased weakness.

Primary progressive MS occurs when the affected individual develops a progressive disease from the beginning without experiencing any relapses or remissions. This subtype of MS affects the spinal cord more than the brain. The most common symptoms are the progressive weakness and stiffness of the legs (progressive spastic paraparesis).

Progressive relapsing MS is the least common type and symptoms include double vision and pain in the eyes, sexual and urinary dysfunction, dizziness, and depression.

MS is diagnosed based on medical history, neurological examination, symptoms, and imaging techniques and laboratory tests. The most commonly used diagnostic criteria requires the presence of damage to the brain and spinal cord over time and space. This means that scars or lesions in the brain or spine must be detected at multiple locations and must have occurred during multiple episodes. These lesions must be located at the white matter of the brain and the spinal cord which is the region made of myelin-covered axons that have a white appearance. In addition, the brain or the spinal cord must also show signs of inflammation. The clinical diagnosis of MS can be supported using imaging techniques such as magnetic resonance imaging (MRI).

Although the diagnosis of MS is mainly clinical, laboratory tests can confirm the diagnosis. The most sensitive imaging test for MS is an MRI which can show the scarring of the white matter. Evoked potential tests are another group of tests that facilitate the diagnosis of MS. These tests evaluate how long the brain takes to respond to sensory stimuli. During an evoked potential test, electrodes are placed on the scalp and detect the electrical signals sent to the brain following auditory, visual, or sensory stimulation. If it takes too long for the brain to respond to the stimuli, it might suggest the presence of inflammation and demyelination. Another useful test is the cerebrospinal fluid (CSF) analysis. CSF is a fluid around the brain and the spinal cord that provides protection for these vital organs. The blood-brain barrier separates the blood and the CSF tightly regulates the content of the CSF. In MS, certain immune proteins can pass through the impaired blood-brain barrier and enter the CSF. A CSF analysis can provide information about the presence of immune cells and proteins in the CFS and support the diagnosis.

The treatment of MS relies on disease-modifying treatments which are specific to MS and symptomatic treatments which are not specific and treat the symptoms. Disease-modifying treatments act on the abnormal mechanism of the disease and reduce the number and severity of relapses. Immunomodulating medications alter the activity of the immune system and anti-inflammatory drugs reduce the inflammation in the brain and spinal cord. These drugs slow the progression of MS but do not stop it.

Acute relapses of MS are commonly treated by corticosteroids. These drugs reduce inflammation and inhibit the proliferation of the immune cells. A group of drugs called beta interferons can also be used to reduce inflammation in relapsing MS. Beta interferons are substances that are naturally produced by the body to reduce inflammation. Other drugs share structural similarities with myelin and alter the immune response to myelin.

A more novel treatment involved monoclonal antibodies. Antibodies are proteins made by immune cells that can recognize and neutralize foreign particles and molecules in the body. Monoclonal antibodies are antibodies produced by identical cells that can identify the desired cell type and destroy it. The exact mechanism of action of monoclonal antibodies in MS is not known. However, they likely inhibit the immune cells from attacking the myelin sheath and have shown to be effective in relapses.

Progressive forms of MS are more difficult to treat and fewer drugs have been found. A cancer chemotherapeutic drug which alters the activity of the immune system appears to be effective in reducing the progression of progressive MS subtypes.

While disease-modifying drugs change the activity of the immune system, symptomatic treatments target the symptoms that occur as a result of damage to the brain and the spinal cord.

Multiple sclerosis is often not fatal and life expectancy is shortened by only a few months. However, quality of life might be affected as a result of neurological deficits. About one-third of all patients with MS go through life without any persistent disability and suffer only intermittent, transient episodes of symptoms.

Goldenberg MM. Multiple sclerosis review. P T. 2012;37(3):175–184. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351877/

Loma I, Heyman R. Multiple sclerosis: pathogenesis and treatment. Current Neuropharmacology. 2011;9(3):409–416. doi:10.2174/157015911796557911

Huang WJ, Chen WW, Zhang X. Multiple sclerosis: Pathology, diagnosis and treatments. Experimental and Therapeutic Medicine. 2017;13(6):3163–3166. doi:10.3892/etm.2017.4410

Dobson R, Giovannonib G. Multiple sclerosis – a review. European Journal of Neurology. 2019;26:27–40. doi:10.1111/ene.13819

Baecher-Allan C, Kaskow B, Weiner H. Multiple Sclerosis: Mechanisms and Immunotherapy. Neuron. 2018; 97: 742-768. https://doi.org/10.1016/j.neuron.2018.01.021

Lemus H, Warrington A, Rodriquez M. Multiple Sclerosis Mechanisms of Disease and Strategies for Myelin and Axonal Repair.Neurologic Clinics. 2018; 36(1):1-11. https://doi.org/10.1016/j.ncl.2017.08.002

Rolak LA. Multiple sclerosis: it's not the disease you thought it was. Clinical Medical Research. 2003;1(1):57–60.DOI https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1069023/

Ghasemi N, Razavi S, Nikzad E. Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy. Cell J. 2016;19(1):1–10. doi:10.22074/cellj.2016.4867