When the body’s immune system starts attacking on protective coverings of nerve fibers, called Myelin sheath, causing damage, scarring, and inflammation in nerves, it is called Multiple Sclerosis. It is considered a chronic autoimmune disorder that directly affects the central nervous system i.e. brain and spinal cord. Disruption of myelin sheath causes damage to transmit electrical impulses between the spinal cord, brain, and the other body parts leading to various severe neural disorders such as cognitive impairment, tiredness, fatigue, numbness, and miscoordinations. It also affects your muscles causing difficulty in walking and speech. Medical researchers are working to find out the actual cause of the Multiple Sclerosis but till the time the exact cause of this nervous disorder is unknown. You may manage its severe symptoms with the help of some treatments, discussed in this article.
Introduction to Multiple Sclerosis (MS)
Multiple sclerosis is a severe condition of the disturbed nervous system because this disorder originates from the destruction of the myelin sheath, which is the outermost protective layer of nerve fibers. Damaging the myelin sheath opens up a wider way for inflammation and temporary lesions. It may scar your tissues if it persists for a long time and can make it difficult for your brain to coordinate your brain with the rest of the body. The cure for Multiple Sclerosis is still unknown but you can manage its slow progression by seeking medical help from your healthcare specialist.
Definition of MS
The disorder is marked with a decreased nerve function leading to inflammation initially and scarring of nerves eventually is known as Multiple Sclerosis. Multiple sclerosis shows severe symptoms that progress into episodes of crisis alternating with relative episodes due to the damage to the protective layer of nerve fibers.
An Autoimmune Disease
Multiple sclerosis is the malfunction of the immune system because the immune system attacks the body’s nervous system and destroys the outer covering (myelin sheath) of nerve fibers leading to difficulty in coordination between the brain and other body parts. If remains untreated for a long time, MS causes a permanent deterioration of nerve fibers, cousing nervous and communication issues.
Impact on the Nervous System
It impacts the health of muscles, eyes, and brain by damaging cognitive abilities, and vision and causing weakness of muscles. This disease progresses slowly and eventually deteriorates the whole CNS.
Types and Sub types of Multiple Sclerosis
MS is an unpredictable disease that affects the brain, spinal cord, and optic nerves. It comes in different forms including primary progressive MS, secondary progressive MS, clinically isolated MS, and relapsing-remitting MS. Prediction of multiple sclerosis is very difficult because it comes in several forms
Clinically Isolated Syndrome
CIS Clinically isolated syndrome is the initial phase of neurological issues faced by anyone, these symptoms last for a maximum of 24 hours or more and the victim feels only one symptom at a time in the majority of cases but in rare cases, more than one symptom also occurs. It is said that it is the start of MS because the early signs of CIS soon convert into severe symptoms of MS. It is the result of demyelination of the central nervous system. If the patient also has lesions along with CIS like in MS, then he is in a danger zone. Reasons for conversion of CIS into MS are still not discovered therefore it is suggested that early treatment of CIS may delay the conversion. Difficulty in walking, swallowing, and speaking along with poor vision and poor coordination are the major symptoms of CIS.
Relapsing-Remitting MS (RRMS)
RRMS( Relapsing-remitting, multiple sclerosis) is a neurological disorder that damages the new neurological functions. Therefore named as relapses or exacerbation. They occur repeatedly often after partial or complete recovery or remission. It is the most common type of MS and 80 percent of MS patients are diagnosed with RRMS. Its progressive form is categorized as secondary progressive MS.
Primary Progressive MS (PPMS)
PPMS is a condition in which neurological function is disrupted to a great extent even disability symptoms appear with the increasing worsening neurological function. Almost 10 to 15 percent of MS patients are diagnosed with PPMS. There are no early relapses therefore the symptoms of PPMS vary from person to person. Each person experiences unique symptoms. The disorder has a short stability period that may be along with or without relapses or remission. Periods of increasing disability also appeared with or without new lesions on an MRI.
Secondary Progressive MS (SPMS)
Some patients of RRMS go on to have secondary progressive multiple sclerosis courses. In this condition, neurological disability increases over time, and neurological function declines progressively. Each person experiences unique symptoms. In SPMS, patients have occasional relapses and discontinuous periods of stability as well.
Etiology and Risk Factors
MS is an inflammatory disorder that affects the central nervous system due to the interaction between genetic susceptibility and the environment. The possibility of developing MS is closely related to genetic, dietary, epidemiological, and environmental risk factors. These risk factors may include parasitic infection, gut microbiota, smoking, air pollution, migraine, age, sex, viral infection, diet obesity, or some autoimmune diseases.
Genetic Predisposition and Familial Clustering
People with a family history of MS are at higher risk of developing Multiple Sclerosis but it is a fact that it is not a genetic disease. So some genetic factors predispose people to develop MS. Recent research has revealed that the main susceptibility allele to MS is leukocyte antigen (HLA) and homozygous carriers of the said gene have a 6-fold increase in the risk of developing MS. According to studies there are more than 200 non-HLA single nucleotide polymorphisms present near genes that enhance the immunity to increase the risk of MS.
Autoimmune Hypothesis of MS Development
Rheumatoid arthritis, thyroid disease, vitamin B12 deficiency, anemia, diabetes, and inflammatory bowel disease are known as autoimmune diseases. These may occur with Multiple Sclerosis, particularly in women. These autoimmune diseases may occur with MS symptoms due to similarities in genetic pathways or environmental exposure.
Migraine: Developing MS is correlated with a positive history of migraine. It is suggested that migraine may be a risk factor for developing MS because the pathogenesis of this relationship is still under observation. But it is also a hypothesis that MS is the cause of Migraine headaches.
Parasites: Parasites are known as helminths and are considered the inhibitors for MS symptoms. They include a variety of worms that are responsible for dampening the immunological responses. So a statement was given about the fact that the incidence of MS has been increased in the countries where the living conditions are more hygienic and cleaner.
Environmental Triggers and Their Role in MS Pathogenesis
Smoking: Research shows that smoking has a major role in increasing the risk of MS. MS and smoking has a clear dose-response relationship and the symptoms of relapsing-remitting MS have a greater enhancement after getting clinically isolated syndrome. There is a great decline observed in MS after quitting smoking.
Air Pollution: Air pollution shows a strong association with MS. Although air pollution is not the major cause of MS but carbon monoxide, sulfur dioxide and lead exposure trigger the inflammatory responses in the lungs and as a result, the release of cytokines occurs that may cause the development of MS.
Diagnosis and Evaluation
By determining “lesions disseminated in space and time” you can diagnose MS. It means that diagnosis with clinical criteria will locate the plaques occurring in different parts of the central nervous system. This needs MRI and spinal fluid analysis. This is the most reliable way to diagnose MS with speedy treatment but the most important is to keep in mind that diagnosis of MS is a very complex task. So careful follow-up of the patient is necessary.
Diagnostic Criteria for MS
Diagnostic criteria for MS have been evolving since 1965 and it ended in 2001 when McDonald’s criteria came into being to describe the mechanism of diagnosis for MS. This idea has been revised in 2005, 2010, and 2017 with the association of National MS Society of America’s panel. These revisions make the diagnosis more rapid and make it possible to treat the MS at early stages.
Role of Clinical Presentation, Imaging, and Laboratory Tests
A neurologist never coincides with one specific physical finding, symptom, or laboratory test but he relies on the exclusion of other causes and symptoms that may otherwise suggest MS and are accompanied by red flags that point to an unifying diagnosis. The symptoms of MS appear and disappear, they vary from person to person. Therefore diagnosing MS is a time-tasking procedure. Ms is diagnosed by clinical diagnosis, hence laboratory testing and RI are not required but to give high sensitivity to MRI findings and response to therapy, it is universally conducted when needed.
Treatment Approaches and Management
Multiple sclerosis has two aspects of treatment. Immunomodulatory Therapy (IMT) is the treatment used to treat immune disorders. It tends to reduce the frequency of relapses by slowing down the progression. The second aspect is to relieve or modify the symptoms, and to cure them properly. To treat early-release MS one may get guidelines through McDonald’s criteria of diagnosis.
Disease-Modifying Therapies (DMTs)
Evidence has been provided that treatment of clinically CIS with drug teriflunomide delays conversion to MS. According to an experiment, onset of MS symptoms within ninety days of randomization showed two or more characteristics of MS. Patients receiving 7 mg of drug per day had 35 percent reduction in the risk of conversion of CIS into MS. So it may be correct to suggest that patients of MS are best served by a multidisciplinary approach and require consultation with specialists as well.
Results from the multi center trials provide evidence that treatment of clinical CIS has given the wide spectrum of clinical manifestations that MS can produce therefore patients may require consultations with a variety of specialists. Indeed, patients with MS are often best served by a multidisciplinary approach.
Research Advances and Future Directions
The landscape of multiple sclerosis is evolving rapidly. New in addition to expanding pipelines of agents with novel mechanisms provide more options for disease-modifying therapies with improved efficacy. Concerted efforts for drug discovery for progressive MS are underway. Researchers are continuing to develop agents for remyelination. Further working to guide DMT initiation and sequencing to determine the role of stem cell transplantation in relapsing is going on. Here you can get a review about these updates.
Emerging Therapies and Treatment Modalities
Disease-modifying therapies are formulated to lessen the risk of new MS plaques in CNS. They are also used to slow down the disability and brain volume mass. BT inhibitors strategy is the most emerging therapy to treat relapsing-remitting MS and it works by modulating B-cells that play the role of immune cells in the nervous system.
Stem cell transplantation is used to destroy the MS patient’s immune system and replace it with transplanted healthy cells. The research continues to find out the effectiveness of these therapies to reduce MS or to reset the immune system. This therapy has some side effects including fever and infection. Continued researches shows side effects, benefits, and safety from MS by using therapeutic drugs that can delay the disability caused by MS.
Stem Cell Therapy, Immunomodulatory Agents, and Neuroprotective Strategies
Stem cell therapy is the transplantation of stem cells collected from various tissues into patients for therapeutic effect. Multiple factors influence the choice of cell type such as appropriate mechanism of action and optimal outcomes.
Neuroprotection is the protection of nerve cells from inflammation during multiple sclerosis. It also causes demyelination and nerve damage. In MS, nerves of the brain and spinal cord are attacked and demyelinated. These nerves are exposed to inflammatory chemicals that cause nerve cell death
The disease-modifying drugs reduce inflammation resulting in demyelination in relapsing-remitting MS, but they are not useful to treat progressive forms of MS. Researchers are continuously striving to find out the way to stop nerve destruction and further related problems of MS.
