Multiple Sclerosis

According to the Atlas of multiple sclerosis issued by multiple sclerosis international federation, where  124 countries around the world are included, the estimated number of people with multiple sclerosis in the world has increased to 2.3 million, with a prevalence that varies considerably, from high levels in North America and Europe to low rates in Eastern Asia and sub-Saharan Africa. Women are twice as likely to have the disease as men, although in some countries women are three times as likely to have multiple sclerosis. Most people are diagnosed between the ages of 25 and 35, although around three to five per cent of people with multiple sclerosis are diagnosed as children, and it can occur in much older adults.

Overview

Multiple sclerosis(MS) or demyelinating disease is a disorder of the central nervous system where the coating around nerve fibers called myelin is damaged. One theory explains  multiple sclerosis is due to the immune system, which mistakes myelin for a foreign body and attacks it.

The attacks cause an inflamed myelin sheath, which subsequently leads to the formation of small areas of damage or changes on the myelin sheath called lesions, and nerve fibers with a disrupted function.

These disrupted functions lead to interruption of the nerve impulses traveling to and from the brain and spinal cord, causing a wide variety of symptoms of MS.

 Each person with the condition is affected differently. Some people's symptoms develop and worsen steadily over time, while for others they come and go. Periods when symptoms get worse are known as relapses. Periods when symptoms improve or disappear are known as remissions. Multiple sclerosis tends to take one of three clinical courses or types each of which might be mild, moderate or severe.

 Relapsing-remitting is the most common form of multiple sclerosis characterized by partial or total recovery after relapses. Primary progressive is the course where symptoms generally do not remit, and is with gradual onset and steady progression. Secondary progressive is a relapsing-remitting course which later becomes steadily progressive.

Several factors could be causing MS, these include a combination of genetic, immunological and environmental factors. People between the ages of 15 and 60 are the most vulnerable category for MS,despite the fact that it could occur at any age. Race, climate, certain autoimmune diseases and smoking are some of the risk factors that are associated with more severe case of the disease and more rapid disease progression.

 

Multiple sclerosis can cause a wide range of symptoms and can affect any part of the body. Some of the most common symptoms include fatigue, vision problems, numbness and tingling, muscle spasms, stiffness and weakness, problems with thinking, learning and planning, depression and sexual problems. Most people with multiple sclerosis only have a few of these symptoms.

While no single test can diagnose multiple sclerosis, several tools are used to determine if a person has the condition, and to rule out other possible causes of whatever symptoms the person is experiencing. These include a thorough medical history, a

a complete neurological examination, which includes looking for abnormalities, changes or weakness in vision, eye movements

 and various tests including magnetic resonance imaging (MRI), evoked potential test and spinal fluid analysis.

Treatment of MS focuses on managing the symptoms rather than curing it, since there is no definite cure for MS. These work on reducing fatigue, treating relapses with steroid medication and treatment to reduce the number of relapses called disease-modifying therapies. Some people have such mild symptoms that they need no treatment.

Complications of multiple sclerosis are secondary symptoms that result from primary symptoms such as bladder dysfunction that could lead to repeated urinary tract infections.. Tertiary symptoms are complications with a higher influence on the individual’s life such as depression.

There is no known way to prevent the onset of multiple sclerosis. However, a recent review shows that increasing vitamin D levels and smoking avoidance have the potential to substantially reduce multiple sclerosis risk and influence disease progression.

The past 20 years have provided considerable improvement for  life quality of people with multiple sclerosis. Fatality is rare with MS, but death usually results from complications, such as breathing problems or renal infections.

The estimated number of people with multiple sclerosis in the world has increased to 2.3 million. Among countries, prevalence drastically varies, with high levels found in North America and Europe to low rates in Eastern Asia and sub-Saharan Africa, as published in the Atlas of multiple sclerosis, that is issued by multiple sclerosis international federation. Multiple sclerosis is two to three times more likely to occur in women than in men.

 


 





 

 

 

Definition

Multiple sclerosis is a lifelong condition that can cause serious disability to the central nervous system; the brain and the spinal cord. It is thought to be an autoimmune disease where the body's immune system destroys the coating around the nerve fibers called myelin. The damaged myelin forms scar tissue (sclerosis), which gives the disease its name. When any part of the myelin or nerve fiber is damaged or destroyed, nerve impulses traveling to and from the brain and spinal cord are distorted or interrupted, producing a wide range of symptoms.

Subtypes

Multiple sclerosis affects everyone differently; it may start with individual relapses; attacks of new or worsening symptoms 

or with gradual progression. It divides into three courses also called types, relapsing-remitting, primary progressive, and secondary progressive.6,5,25

Relapsing-remitting (RRMS)

Most people with multiple sclerosis have a relapsing-remitting disease course. A patient with relapsing remitting will have relapses, which develop over days or weeks or even months and are usually followed by partial or complete improvements called remission, within the same length of time as a relapse’s duration and sometimes up to years.

 

Secondary progressive(SPMS)

Secondary progressive is a continuous buildup of disability, independent of any relapses. The name is derived from an onset of progression towards more disability that begins second, after the relapsing remitting stage. 'Progressive' is the word used to describe the change towards more disability.  Rates of progression are vary drastically..

However, in rare cases, patients may be diagnosed with secondary progressive from the very beginning because they have experienced relapses in the past but these may have been mild or their significance was missed.

Primary progressive

This subtype is accompanied by  steady, gradual ,progressive symptoms from the very start, without any relapses. This type of Multiple sclerosisis usually diagnosed in older ages than the average age for relapsing remitting.

 

Clinically isolated syndrome is a term used refers to a first episode of inflammatory demyelination in the central nervous system that could become multiple sclerosis in the case of additional activity .

Causes

The exact cause of multiple sclerosis is still unknown. Scientists believe that the interaction of several different factors may be involved. These include a combination of genetic, immunological and environmental factors. Understanding what causes multiple sclerosis will speed the process of finding more effective ways to treat it or even prevent it from occurring in the first place.

Risk Factors
  1. Immunologic Factors

 

These attacks cause inflammation which leads to the formation of small areas of damage or changes on the myelin sheath called lesions. These lesions can disrupt the messages travelling along the nerves. More research is needed for additional explanation for the reason behind this condition. 

 

  1. Genes and family history

 

Although indirectly inherited, having a first-degree relative such as a parent or sibling with multiple sclerosis does significantly increase an individual's risk of developing the disease. There's no single gene that causes it, but some researchers have shown that presence of certain genes will increase the risk to develop the multiple sclerosis, especially when triggered by environmental factors.

 

 

  1. Environmental factors

 

  • Climate and vitamin D

Regardless of any ethnic backgrounds, the incidence of the disease is lower in the equatorial regions of the world than in the southernmost and northernmost regions. Countries where the disease is more common include Canada, the northern United States, New Zealand, southeastern Australia and Europe. These countries are far from the equator which means that they are less exposed to sunlight and vitamin D levels.

 

  • Infections

 More than a dozen viruses, bacteria and other microbes such as Epstein-Barr; the most common human virus that causes glandular fever and Chlamydia pneumonia;  causes mild pneumonia or bronchitis in adolescents and young adults, have been linked to multiple sclerosis, but none have been definitively proven responsible for triggering MS. Most people have been subjected to such infections at least once in their lives, and therefore they are not direct causes of MS.  

 

These factors may increase the risk of developing multiple sclerosis:

  • Age

 Although it can occur at any age, people with age ranges of 15 and 60 years are most commonly affected.

  • Sex

 Women are twice more likely to have the disease than men.

  • Race

 People of Asian, African or Native American descent have the lowest risk of developing multiple sclerosis. White people, particularly those of northern European descent have the highest risk.

  • Certain autoimmune diseases

 Having certain immune disease such as thyroid disease, type 1 diabetes or inflammatory bowel disease may slightly increase the risk of developing multiple sclerosis.

  • Smoking

 Studies have shown that smoking increases a person’s risk of developing multiple sclerosis about two folds, and smokers are commonly associated with more severe symptoms and more rapid disease progression, maybe due to the chemicals found in cigarettes. Furthermore, passive smokers; people breathing in other people's smoke, are at a higher risk of developing MS.

  • Obesity

 Studies show that very overweight or obese people are more related to multiple sclerosis. Possible reasons for this are that obese people often have low levels of vitamin D and are more linked to immune system disease. Other possible reasons could cause MS but not well understood yet.

Pathophysiology

Multiple sclerosis is an inflammatory, demyelinating; a loss of myelin with relative preservation of axons, disease of the central nervous system. Multiple sclerosis occurs when myelin sheaths that surround the nerve fibers, and are responsible for their protection, in addition to facilitating electrical signals to pass from the brain to the rest of the body, are attacked by the immune system. Some cases include the attack of axons as well. The location of lesions usually defines the type of clinical deficit that results.

The attacks lead to an inflamed myelin sheath, followed by small lesions formation, in addition to an interrupted function of the nerve fibers; this disruption leads to the symptoms and signs of multiple sclerosis.

Lesion formation begins with the breakdown of the blood-brain barrier; a group of cells forming the walls of brain capillaries that stop free diffusion of blood substances into the brain

. Inflammatory cells, mainly lymphocytes and macrophages, are thought to be able to penetrate the blood-brain barrier due to enhanced expression of adhesion molecules on the surface of these cells.

Plasma cells infiltrates that do produce antibodies in variable amounts have been linked to lesion formation in MS..

During remissions symptom’s recovery is mainly due to remyelination, while some function recovery could be due to nervous system plasticity;  the ability of the nervous system to rewire its connections..

 

Signs And Symptoms

 

The signs and symptoms of multiple sclerosis vary greatly from person to another, and each individual’s symptoms can change or fluctuate over time, depending on the location of the affected nerve fibers. No two patients with MS have identical symptoms since they are unpredictable and variable. Common symptoms  include:

 

  1. Vision problems

Blurred vision;  loss of sharpness of vision and the inability to see fine details.

, poor contrast, prolonged double vision; seeing two images of a single object, color vision deficiency,  partial or complete loss of vision are usually present in one eye at a time. They often involve eye pain during eye movement. These usually are the first symptoms of multiple sclerosis in many people.

 

  1. Sensory problems

The impairment of sensory perception includes the loss of feeling in limbs and other areas. The sensations can include tingling, crawling sensations over the skin, numbness or tightness, and sometimes pain. Another sensory symptom is feeling an ‘electrical rush’ radiating from the neck and down the spine, when the head is flexed towards the chest, which is known as Lhermitte’s Sign. Uhthoff's Sign includes visual disturbances mostly, in addition to motor or sensory symptoms.

 

  1. Pain

Pain syndromes are common in multiple sclerosis and are often described as stabbing, burning, tingling or pins and needles. Two main types of pain that can occur are neuropathic and musculoskeletal. The neuropathic type is caused by the disease itself due to damage to the nervous system where medication may be prescribed. Patients with the musculoskeletal type may be referred to a physiotherapist for their back, neck and joint pain that can be indirectly caused by multiple sclerosis, particularly for people who have movement problems overloading their lower back or hips and.

 

  1. Tremor

 

Tremor is an uncontrollable rhythmic, trembling or shaking movement, which occurs due to lesions in the cerebellum, the area of the brain responsible for balance and co-ordination of movement. Tremor can vary from very mild or hardly noticeable to completely debilitating. It can be classified into intention tremor that occurs during movement, postural tremor that occurs while holding a position like sitting, and resting tremor occurring at rest. The most frequent type linked multiple sclerosis is intention tremor that worsens as the individual reaches for an object.

 

 

  1. Walking (Gait) Difficulties

Related to several factors including weakness, spasticity; signals from the brain are interrupted keeping the muscle in its shortened, contracted state and is much more common in the legs. Furthermore, loss of balance and spasms are also possible factors, where the latter are similar to spasticity but contract and relax very suddenly. .

 

  1. Fatigue

Extreme tiredness and sense of exhaustion is one of the most common symptom of multiple sclerosis that occurs in most of patients with MS. It is with a high impact on an individual’s life, making it hard to perform the simplest activities in daily life..

 

  1. Dizziness and Vertigo

Dizziness, the most common symptom of MS, in multiple sclerosis cause people to feel off balance or lightheaded, or to a lesser extent vertigo; the sensation that they or their surroundings are spinning, . Balance problems could be short-term or  may last longer. Despite the fact that  no specific medications exist for balance, other conditions causing this problem should be ruled out, such as inner ear infection..

 

  1. Cognitive Changes

They refer to a range of high-level brain functions affected in almost half of people with multiple sclerosis, including problems with remembering and learning new things, information processing, problem solving, word-finding, and concentration. Not everyone with MS will develop cognitive problems, and these will range from mild to progressively worse during relapse.

  1. Bladder and bowel problems

Bladder dysfunction is one of the most common symptoms in multiple sclerosis, including urinating more frequently, frequent night urination, having a sudden, urgent need to urinate, which can lead to unintentionally passing urine difficulty in complete emptying of the bladder and recurrent urinary tract infections. Constipation is the most common bowel problems in multiple sclerosis, where stools are passing much less frequently than normal. The other bowel problem is incontinence; lack of control over the bowel opening. Both are linked but not necessarily do they lead to each other.

 

 

 

       10) Sexual Problems

Multiple sclerosis affects the practical and emotional aspects of sex, for both men and women. Sexual responses can be affected by damage in the central nervous system associated with the condition, as well by symptoms such as fatigue and spasticity.

 

  1. Depression

Clinical depression, the severest form of depression, is one of the most common symptoms of multiple sclerosis. It may be related directly to the disease itself or can be due to the stress of having to live with a chronic condition, or both.

 

  1. Speech and swallowing problems

Swallowing problems, also called dysphagia, cause difficulty chewing or choking when eating and drinking, and come as a result from nerves destruction for those controlling the many small muscles in the mouth and throat. Speech disorders can arise commonly later in the disease course and during periods of extreme fatigue. They include slurring of speech due to weakness or lack of coordination in the muscles used in speech called dysarthria. Speech difficulties could occur during any stage but are more frequent during late stages. Stuttering could also be one of the problems related to MS.

 

 

 

Diagnosis

Diagnosis of multiple sclerosis

 

Diagnosing multiple sclerosis is challenging, since there are no symptoms, physical findings or laboratory tests that can positively confirm multiple sclerosis. Instead, a diagnosis of multiple sclerosis often relies on excluding other conditions that have similar signs and symptoms, known as a differential diagnosis.

Only a neurologist, a specialist in conditions of the nervous system, is capable of making the diagnosis. This process is likely to start with a thorough medical history and a complete neurological examination, which includes looking for abnormalities, changes or weakness in vision, eye movements, hand or leg strength, balance and co-ordination, speech and reflexes. Once a neurologist strongly suspect multiple sclerosis, other tests are used to confirm the diagnosis of multiple sclerosis, including:

 

  • Blood tests

This helps in excluding other conditions that cause demyelination in the central nervous system with symptoms similar to multiple sclerosis such as viral infections, side effects from high exposure to certain toxic materials, severe vitamin B12 deficiency and a condition of autoimmune diseases known as collagen-vascular diseases.

  • Lumbar puncture

 Also called a spinal tap, describes a procedure that includes a sample of cerebrospinal fluid, which flows around the brain and spinal cord, to be tested for changes in the cerebrospinal fluid. These abnormalities can help diagnose multiple sclerosis or rule out other conditions with similar symptoms.

  • Magnetic Resonance Imaging (MRI)

 Represents the most sensitive and non-invasive way of imaging the brain and spinal cord. It reveals any lesions or scarring of the myelin sheath surrounding nerves in the brain and spinal cord. This provides diagnosis confirmation in most people with multiple sclerosis.

 

  • Evoked potential test

It is an electrical test that measures the time needed for stimuli response by the nervous system  via placing small electrodes on the head. The time it takes for messages to travel to and from the brain is recorded, which is slower with myelin damage. Visual stimuli are the most commonly used in the diagnostic process, which evaluate how well the eyes work.

 

People with relapsing-remitting type are usually diagnosed more easily based on a pattern of symptoms and also can be confirmed by other tests such as MRI. However, diagnoses can be more difficult and it might  take a few years in a person with unusual symptoms or progressive types, due to the slow worsening of the condition..

 

 

Treatment


At this time, there is no cure for multiple sclerosis. Treatments typically help manage symptoms, speed recovery from relapses, and decrease the number of relapses. Treatment usually depends on the type and severity of symptoms, in addition to difficulties the person has. They may include:

 

  • Managing relapses of multiple sclerosis

Attacks or relapses are controlled through the following:

  1. Corticosteroids

 They are anti-inflammatory drugs that work on reducing nerve inflammation. Severe cases usually involve either a three-to- five-day course of injections of steroid given in hospital such as methylprednisolone or a five-day course of oral steroid taken at home such as prednisone. Steroids are prescribed to speed up recovery from a relapse, but they cannot stop future relapses nor do they prevent MS progression.

  1. Plasma exchange

It is also called plasmapheresis, where the plasma, the liquid portion of blood, is filtrated from blood cells using  centrifugation that makes use  of different specific gravities of blood components, or semipermeable membranes that use variable particle sizes for filtration. Later on , the collected blood cells are mixed with a protein solution (albumin) and returned into the body. Plasma exchange may be used for new or severe symptoms, and to treat relapses that haven't responded to steroids.

 

 

  • Managing symptoms of multiple sclerosis

Some symptoms can be minimized or controlled in many ways as mentioned below:

  • Physical therapy

 Muscle spasms and spasticity, fatigue, weakness, balance problems, walking or mobility, and dizziness can be improved with physiotherapy, such as stretching and strengthening comprised exercises. Special exercises called vestibular rehabilitation can help with  balance problems . These are all done based on occupational therapists evaluation and recommendations.

 

-Muscle relaxants

 

 Medicine that help to relax any muscle spasms and stiffness, especially in the legs, may be prescribed, such as baclofen, gabapentin, tizanidine, or diazepam.

 

-Medications to reduce fatigue

 

  Since fatigue is a common symptom of multiple sclerosis, medications may be prescribed such as amantadine. These medications usually function along with other treatment measures including exercise, keeping healthy sleep patterns, and avoiding medications that can contribute to fatigue like painkillers.

 

-Other medications

 

 Hereunder are some medications used to help manage the common symptoms of multiple sclerosis:

  • Bladder Problems

-Desmopressin.

-Ciprofloxacin.

  • Bowel Dysfunction

-Magnesium hydroxide.

-Docusate.

  • Sexual problems

-Tadalafil.

-Vardenafil.

  • Walking (Gait) Difficulties

-Dalfampridine.

  • Visual problems:

-Gabapentin.

 

 

 

 

 

  • Disease-modifying therapies

These include medicines used to reduce the number and severity of relapses. Disease-modifying therapies are not suitable for everyone with multiple sclerosis since they are only prescribed to those with relapses including relapsing-remitting, as well as progressive forms of multiple sclerosis in those people who experience relapses:

  • For primary-progressive multiple sclerosis, disease-modifying therapies are not recommended. Some people, however, with progressive form who continue to have disabling relapses may benefit from taking ocrelizumab; the only FDA-approved disease-modifying therapy. It slows worsening of disability in people with this type of multiple sclerosis.

 

  • Several disease-modifying therapies are available for relapsing-remitting multiple sclerosis, treatment options include:

 

  1. Beta interferons

These medications are among the most commonly prescribed medications to treat multiple sclerosis. They are injected under the skin or into muscle in order to reduce the frequency and severity of relapses. Neutralizing antibodies formation is possible when taking such medication, that can reduce drug effectiveness.

  1. Glatiramer acetate

 This medication is injected underneath the skin to  cause  a possible block of the immune system attack on myelin.

  1. Teriflunomide

Teriflunomide is a tablet taken once a day and is used if a recent relapse is encountered, and/or MRI scans reveal an active MS. Teriflunomide can cause liver damage, hair loss and other side effects. It shouldn’t be used during pregnancy or when not using appropriate contraception by both partners.

  1. Natalizumab

Natalizumab is injected into a vein once every 28 days to stop potentially damaging immune cells moving from the bloodstream to the brain and spinal cord. This medication increases the risk of a viral infection of the brain called progressive multifocal leukoencephalopathy in some people. It is the first line treatment for people with severe MS or rapid deterioration of the case, and in the case of two or more severe relapses a year with MRI images to prove worsening of the case.

  1. Fingolimod

This once a day oral medication reduces relapse rate.  It is used when other medications are not effective in reducing the frequencies of relapses, and in some cases they are increased.

Heart rate monitoring  is needed for six hours after the first dose because the heartbeat may be slowed.

 

 

 

Complications

Complications are the secondary symptoms that result of primary symptoms. For example:

  • Repeated urinary tract infections happen as a result of bladder dysfunction .
  • Disuse weakness, loss of muscle tone poor trunk control, decreased bone density and shallow, inefficient breathing could all occur due to inactivity.
  • Pressure sores or bedsores could be the downsides of immobility.

Further progression of MS could lead to serious symptoms with a bigger impact, called tertiary symptoms that include:

  •  Social, vocational and psychological complications such as inability to walk or drive could make it hard to maintain a usual job, damaged relationships and isolation due to stressful aspects of MS.
  • Depression, very common in people with MS, may be either a symptom or complication as it can be caused by the disease process itself and/or triggered by the psychological complications.
Prevention

Although there is no known way to actually prevent the onset of multiple sclerosis, a review that was published in Nature Reviews Neurology, shows the associations between multiple sclerosis and environmental, lifestyle and dietary factors. Vitamin D nutrition and cigarette smoking are modifiable by which increasing vitamin D levels and avoiding smoking can substantially reduce MS risk and influence disease progression. A well established understanding of the environmental factors involved in multiple sclerosis will have an impact on finding new and more-effective approaches  for prevention.

Prognosis

The type, duration, severity and impact of symptoms are variable among individuals. In fact, it is very difficult to predict the course of multiple sclerosis. Some people will go for long periods with few or no symptoms whilst others will experience more frequent or persistent problems.

However, treatments over the past 20 years have considerably improved the quality of life of people with the condition.

Male patients with primary progressive MS have the worst prognosis since they respond less treatment and their disability progresses rapidly.

Fatality is rare in MS, but complications from severe cases usually lead to, such as breathing problems or renal infections.

According to the National Health Service(NHS), the average life expectancy for people with MS is lower by 5 to 10 years than average, which is decreasing with time.

Epidemiology

According to the Atlas of multiple sclerosis issued by multiple sclerosis international federation, where  124 countries around the world are included, the estimated number of people with multiple sclerosis in the world has increased to 2.3 million, with a prevalence that varies considerably, from high levels in North America and Europe to low rates in Eastern Asia and sub-Saharan Africa. Women are twice as likely to have the disease as men, although in some countries women are three times as likely to have multiple sclerosis. Most people are diagnosed between the ages of 25 and 35, although around three to five per cent of people with multiple sclerosis are diagnosed as children, and it can occur in much older adults.