Multiple sclerosis: a distressing disorder
Multiple sclerosis (MS) is a chronic disease of the central nervous system. It is believed to be an autoimmune disease where the body destroys myelin, which surrounds the neurons. Its symptoms can range from vision problems, tingling in hands and feet, to impaired walking, numbness and other motoric deficits. The symptoms can remain dormant for years, and while it is typically diagnosed around the age of 20, it can lurk until the age of 50.
Myelin at risk
Although the exact triggers for the onset of this condition are still unknown, the mechanism of progression of the multiple sclerosis is determined by myelin deterioration, the protective fatty tissue that wraps around nerve fibers in sheaths, insulating them so they can conduct electric signals fast and without information loss. This is important because the brain orchestrates every movement of the body and responds to stimuli with great precision and speed. Neurons are the cables with which the information travels, and myelin is the insulating wrapper that enables long distance communication between the brain and the furthest reaches of the human body – fingers and toes.
The underlying mechanism of myelin degradation is thought to be either its destruction by the immune system, or the failure of myelin-producing cells called oligodendrocytes (For more about oligodendrocytes, read this article!).
Figure 1: Symptoms of MS. Picture by Mikael Häggström, used with permission.
Neurological symptoms in patients with multiple sclerosis (MS) can vary significantly, ranging from vision problems, tingling in the hands and feet, to difficulty walking, numbness, and other motor deficits. Specific symptoms are determined by the location in the central nervous system where the myelin has been lost and may include blurry vision, heightened reflexes, loss of sensitivity, changes in sensation, difficulties in movement, coordination and balance, speech problems, acute and chronic pain, and many more.
Difficulties thinking and depression or mood swings are also common. Patients can, especially in later stages of MS, experience memory loss, slowed information processing, and fatigue, but language, intelligence and general knowledge (semantic memory) stays unaffected.
The condition begins as a clinically isolated case of motor or sensory problems (45% of patients), visual impairments (20% of patients) or balance and coordination problems (10% of patients) which can last for up to a month, either as a progressively worsening phenomenon, or as relapses. A combination of the two can also occur.
Relapses are usually not predictable, but occur only up to twice a year, and are more frequent during hotter months. This is known as Uthoff's phenomenon. Other potential relapse triggers include viral infections and stress.
Prior to the onset of MS, patients may experience a phase of psychiatric issues, disorientation, and increased use of healthcare. This condition can last for several years prior to the first onset of MS symptoms.
Characteristics of MS
Multiple sclerosis is characterized by three distinct and interconnected features: formation of lesions in the central nervous system, inflammation and the destruction of myelin sheaths. The lesions are made by the repeated process of remyelination in the areas where myelin has been lost, which inevitably fails and leaves a scar-like plaque around the neurons' axon. These scars are the origin of MS symptoms, where the neurons aren't capable of sending coherent and timed signals to other parts of the human body. With the repeated destruction of myelin and their efforts to remyelinate, inflammation occurs. Additionally, astrocytes are drawn to this inflammated and scarred lesion, complicating further remyelination attempts.
Could it be a virus?
As with all complex conditions, both genetic and environmental factors play a role in MS. The myelin degradation is the final stage, but how and why it occurs is still unknown. Infection by a microorganism has been proposed as one of the causes, but only in people who weren't exposed to this microorganism (or have had low exposure to microorganisms in general) early in life. The so-called „Hygiene hypothesis“ proposes that exposure to microorganisms early in life is protective, and can better shield us after the initial contact, during our whole life. Evidence for a virus as a cause comes in the form of oligoclonal bands in the blood serum and cerebrospinal fluid of more than 95% people with MS, and are associated wit several viruses that are known causes of myelin destruction.
The most significant candidate is the Epstein-Barr virus (EBV), which also infects about 95% of adults. Together with other genetic and environmental factors, it provides a compelling argument for it being the trigger of MS, although this trigger only occurs in a small population of people infected by Epstein-Barr virus. A study on more than 10 million people accumulated between 1993 and 2013 found a 32-fold increased risk of developing MS after infection with EBV, but not other viruses, including the similarly transmitted cytomegalovirus. In short, exposure to EBV later in life, but not during childhood, greatly increases the risk of MS, but is not the only factor.
Clinical trials, cures and hope
A number of studies recently reevaluated has shown the importance of Epidermal Growth Factor (EGF) in the onset of MS. It has been shown that the MS patients have a decreased level of EGF, crucial for myelination and its maintenance. Other clinical trials have shown the importance of cellular coordination in production and maintenance of myelin, and astrocyte health is believed to be of importance to this system. L-glutamate supplementation for astrocytic co-stimulation has been shown to decrease MS symptoms and to prolong the lifespan of animal models.
Furthermore, EGF recruits new cell formation from the existing pool of progenitor cells, including oligodendrocytes, responsible for myelin production, and astrocytes, responsible for health of the central nervous system. Given that EGF is heavily recruited by testosterone, an effective exercise regimen is considered beneficial in MS patients.
Another study lists the benefits of dietary restrictions to mitigate increased oxidative stress, disturbances in energy metabolism and inflammation-like processes, in order to decrease brain aging and overall neurodegenerative disorder factors.
Oligodendrocytes produce myelin every time a person learns something new, be it a dance move, a new language, game or just by reading a book. Being mentally active and improving mental capacity can only benefit both the state of MS, but also the individual's wellbeing and satisfaction. While there are still no definite drugs to treat MS, a number of therapies aimed at lessening the symptoms and recovering lost functions exist. The future looks promising for patients with multiple sclerosis (MS), and with new techniques, the understanding of this extremely complex disease is on the horizon.
3. Bjornevik K, Cortese M, Healy BC, Kuhle J, Mina MJ, Leng Y, et al. (January 2022). "Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis". Science. 375 (6578): 296–301.
7. Prolla, T. A., & Mattson, M. P. (2001). Molecular mechanisms of brain aging and neurodegenerative disorders: lessons from dietary restriction. Trends in Neurosciences, 24(11), S21–S31. doi:10.1016/s0166-2236(00)01957-3
8. Scalabrino, G. Epidermal Growth Factor in the CNS: A Beguiling Journey from Integrated Cell Biology to Multiple Sclerosis. An Extensive Translational Overview. Cell Mol Neurobiol 42, 891–916 (2022). https://doi.org/10.1007/s10571-020-00989-x
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