Multiple sclerosis
Multiple sclerosis is an autoimmune disease resulting in damage to myelin, which are the insulating covers of nerve cells in the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to transmit signals, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. Symptoms include double vision, vision loss, eye pain, muscle weakness, and loss of sensation or coordination.
MS takes several forms of presentation:
- New symptoms can occur as an isolated attack; where the patient experiences neurological symptoms suddenly and then gets better called relapsing-remitting MS which is seen in 85% of patients.
- In other patients symptoms can slowly get worse over time called primarily progressive MS seen in 15% of patients.
- The patients with relapsing- remitting MS can experience gradual worsening of their symptoms following the attacks, this subtype is called secondary progressive MS. In relapsing forms of MS, symptoms may disappear completely between attacks, although some permanent neurological problems often remain, especially as the disease advances. In progressive forms of MS, the body's function slowly deteriorates once symptoms manifest and will steadily worsen if left untreated.
- A patient might have a single attack and not meet the full criteria for being diagnosed with MS. This is called a clinically isolated syndrome.
There is no cure for MS. Current treatments aim to reduce inflammation and resulting symptoms from acute flares and prevent further attacks with disease-modifying medications, aiming at slowing disease progression and improving quality of life. Physical therapy and occupational therapy, along with patient-centered symptom management, can help with people's ability to function. The long-term outcome is difficult to predict; better outcomes are more often seen in women, those who develop the disease early in life, those with a relapsing course, and those who initially experienced few attacks.
New evidence suggests an important role of lifestyle factors in the prognosis of MS, where multiple lifestyle factors have been linked to affecting the expanded disability status scale score depending on patients' age, gender and disease duration.
MS is the most common immune-mediated disorder affecting the central nervous system. In 2020, about 2.8 million people were affected by MS globally, with rates varying widely in different regions and among different populations. The disease usually begins between the ages of 20 and 40 and is almost three times more common in females than in males.
MS was first described in 1868 by French neurologist Jean-Martin Charcot. The name "multiple sclerosis" is short for multiple cerebro-spinal sclerosis, which refers to the numerous glial scars that develop on the white matter of the brain and spinal cord.
Signs and symptoms
MS lesions can affect any part of the central nervous system so a person with MS can have almost any neurological signs or symptoms.Fatigue is one of the most common symptoms of MS. Roughly 65% of people with MS experience fatigue. Of these, some 15–40% report fatigue as their most disabling symptom.
Autonomic, visual, motor, and sensory problems are also among the most common symptoms.
The specific symptoms depend on the locations of the lesions within the nervous system and may include loss of sensitivity or changes in sensation in the limbs, such as tingling, "pins and needles," or numbness; limb motor weakness or pain, blurred vision, pronounced reflexes, muscle spasms, difficulty walking, or with coordination or balance ; problems with speech or swallowing, visual problems, fatigue, and bladder and bowel difficulties, among others. When MS is more advanced, walking difficulties lead to a higher risk of falling.
Difficulties in thinking and emotional problems such as depression or unstable mood are also common. The primary deficit in cognitive function that people with MS experience is slowed information-processing speed, with memory also commonly affected, and executive function less commonly. Intelligence, language, and semantic memory are usually preserved, and the level of cognitive impairment varies considerably between people with MS.
Uhthoff's phenomenon, a reversible exacerbation of patient symptoms following a rise in body temperature, and Lhermitte's sign, an electrical sensation that runs down the back when flexing the neck, are particularly characteristic of MS, although may not always be present. 60–80% of MS patients find that symptoms, such as fatigue, are affected by changes in body temperature. MS may also present with eye movement impairments such as internuclear ophthalmoplegia or sixth nerve palsy.
Measures of disability
The main measure of disability and severity is the expanded disability status scale, with other measures such as the multiple sclerosis functional composite being increasingly used in research. EDSS is also correlated with falls in people with MS. While it is a popular measure, EDSS has been criticized for some of its limitations, such as overreliance on walking.Disease course
Prodromal phase
MS may have a prodromal phase in the years leading up to its manifestation, characterized by psychiatric issues, cognitive impairment, and increased use of healthcare.Onset
85% of cases begin as a clinically isolated syndrome over a number of days with 45% having motor or sensory problems, 20% having optic neuritis, and 10% having symptoms related to brainstem dysfunction, while the remaining 25% have more than one of the aforementioned difficulties. With optic neuritis as the most common presenting symptom, people with MS notice sub-acute loss of vision, often associated with pain worsening on eye movement, and reduced color vision. Early diagnosis of MS-associated optic neuritis helps timely initiation of targeted treatments. However, it is crucial to adhere to established diagnostic criteria when treating optic neuritis due to the broad range of alternative causes, such as neuromyelitis optica spectrum disorder, and other autoimmune or infectious conditions. The course of symptoms occurs in two main patterns initially: either as episodes of sudden worsening that last a few days to months followed by improvement or as a gradual worsening over time without periods of recovery. A combination of these two patterns may also occur, or people may start in a relapsing and remitting course that then becomes progressive later on.Relapses
Relapses are usually unpredictable, occurring without warning. Exacerbations rarely occur more frequently than twice per year. Some relapses, however, are preceded by common triggers and they occur more frequently during spring and summer. Similarly, viral infections such as the common cold, influenza, or gastroenteritis increase their risk. Stress may also trigger an attack.Many events do not affect rates of relapse requiring hospitalization including vaccination, breast feeding, physical trauma, and Uhthoff's phenomenon.
Pregnancy
Many women with MS who become pregnant experience lower symptoms during pregnancy. During the first months after delivery, the risk increases. Overall, pregnancy does not seem to influence long-term disability.Causes
MS is an autoimmune disease with a combination of genetic and environmental causes underlying it. Both T-cells and B-cells are involved, although T-cells are often considered to be the driving force of the disease. The causes of the disease are not fully understood. The Epstein-Barr Virus has been shown to be directly present in the brain of most cases of MS and the virus is transcriptionally active in infected cells. EBV nuclear antigens are believed to be involved in the pathogenesis of multiple sclerosis, but not all people with MS have signs of EBV infection. Dozens of human peptides have been identified in different cases of the disease, and while some have plausible links to infectious organisms or known environmental factors, others do not.Immune dysregulation
MS usually begins when immune cells known as T cells and B cells erroneously attack the body's own nervous system, releasing signals causing inflammation in brain structures. In MS, B cells may be involved, revealed by the presence of certain antibodies commonly found in the spinal fluid of people with MS.Infectious agents
Early evidence suggested the association between several viruses with human demyelinating encephalomyelitis, and the occurrence of demyelination in animals caused by some viral infections. One such virus, Epstein-Barr virus, can cause infectious mononucleosis and infects about 95% of adults, though only a small proportion of those infected later develop MS. A study of more than 10 million US military members compared 801 people who developed MS to 1,566 matched controls who did not. The study found a 32-fold increased risk of MS development following EBV infection. It did not find an increased risk after infection with other viruses, including the similar cytomegalovirus. These findings strongly suggest that EBV plays a role in MS onset, although EBV alone may be insufficient to cause it.The nuclear antigen of EBV, which is the most consistent marker of EBV infection across all strains, has been identified as a direct source of autoreactivity in the human body. These antigens appear more likely to promote autoimmunity in vitamin D-deficient persons. The exact nature of this relationship is poorly understood.