Рассеянный склероз

Рассеянный склероз
Другие имена	Рассеянный церебральный склероз, рассеянный цереброспинальный склероз, рассеянный склероз, диссеминированный энцефаломиелит
CD68-stained tissue shows several macrophages in the area of a demyelinated lesion caused by MS.
Specialty	Neurology
Symptoms	Variable, including almost any neurological symptom or sign, with autonomic, visual, motor, and sensory problems being the most common.
Usual onset	Age 20–50
Duration	Long term
Causes	Unknown
Diagnostic method	Based on symptoms and medical tests
Treatment	Disease-modifying therapies Physiotherapy Occupational therapy
Frequency	0.032% (world)

Рассеянный склероз ( РС ) — аутоиммунное заболевание , при котором изолирующие оболочки нервных клеток головного и спинного мозга . повреждаются Это повреждение нарушает способность частей нервной системы передавать сигналы , что приводит к ряду признаков и симптомов , включая физические, психические , а иногда и психиатрические проблемы. Симптомы включают двоение в глазах , потерю зрения, боль в глазах, мышечную слабость и потерю чувствительности или координации. Рассеянный рассеянный склероз принимает несколько форм, при этом новые симптомы либо возникают в виде изолированных приступов (рецидивирующие формы), либо нарастают с течением времени (прогрессирующие формы). При рецидивирующих формах рассеянного склероза между приступами симптомы могут полностью исчезнуть, хотя некоторые постоянные неврологические проблемы часто сохраняются, особенно по мере прогрессирования заболевания. In progressive forms of MS, bodily function slowly deteriorates once symptoms manifest and will steadily worsen if left untreated.

While its cause is unclear, the underlying mechanism is thought to be either destruction by the immune system or failure of the myelin-producing cells. Proposed causes for this include immune dysregulation, genetics, and environmental factors, such as viral infections. MS is usually diagnosed based on the presenting signs and symptoms and the results of supporting medical tests.

No cure for multiple sclerosis is known. Current treatments are aimed at mitigating inflammation and resulting symptoms from acute flares and prevention of further attacks with disease-modifying medications. 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.

Multiple sclerosis is the most common immune-mediated disorder affecting the central nervous system. Nearly one million people in the United States had MS in 2022, and in 2020, about 2.8 million people were affected globally, with rates varying widely in different regions and among different populations. The disease usually begins between the ages of 20 and 50 and is twice as common in women as in men. 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 (or sclerae – essentially plaques or lesions) that develop on the white matter of the brain and spinal cord.

Signs and symptoms

Main article: Multiple sclerosis signs and symptoms

Main symptoms of multiple sclerosis

As multiple sclerosis (MS) lesions can affect any part of the central nervous system, a person with MS can have almost any neurological symptom or sign referable to the central nervous system.

Fatigue is one of the most common symptoms of MS. Some 65% of people with MS experience fatigue symptomatology, and of these, some 15–40% report fatigue as their most disabling MS symptom.

Autonomic, visual, motor, and sensory problems are also among the most common symptoms.

The specific symptoms are determined by the locations of the lesions within the nervous system, and may include focal loss of sensitivity or changes in sensation in the limbs, such as feeling tingling, pins and needles, or numbness; limb motor weakness/pain, blurred vision, pronounced reflexes, muscle spasms, difficulty with ambulation (walking), difficulties with coordination and balance (ataxia); problems with speech or swallowing, visual problems (optic neuritis manifesting as eye pain & vision loss, or nystagmus manifesting as double vision), fatigue, and bladder and bowel difficulties (such as urinary or fecal incontinence or retention), among others. When multiple sclerosis is more advanced, walking difficulties can occur and the risk of falling increases.

Difficulties 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 worsening of symptoms due to exposure to higher-than-usual temperatures, and Lhermitte's sign, an electrical sensation that runs down the back when bending the neck, are particularly characteristic of MS, although may not always be present. Another presenting manifestation that is rare but highly suggestive of a demyelinating process such as MS is bilateral internuclear ophthalmoplegia, where the patient experiences double vision when attempting to move their gaze to the right & left.

Some 60% or more of MS patients find their symptoms, particularly including fatigue, are affected by changes in body temperature.

Measures of disability

The main measure of disability and severity is the expanded disability status scale (EDSS), 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 relying too much 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

The condition begins in 85% of cases as a clinically isolated syndrome (CIS) 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 previous difficulties. Regarding 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 colour 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 (NMOSD), 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 (called relapses, exacerbations, bouts, attacks, or flare-ups) followed by improvement (85% of cases) or as a gradual worsening over time without periods of recovery (10–15% of cases). 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 have been found not to 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 and fewer relapses. During the first months after delivery, the risk increases. Overall, pregnancy does not seem to influence long-term disability.

Causes

Multiple sclerosis 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 (EBV) 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

Failure of both central and peripheral nervous system clearance of autoreactive immune cells is implicated in the development of MS. The thymus is responsible for the immune system's central tolerance, where autoreactive T-cells are killed without being released into circulation. Via a similar mechanism, autoreactive B-cells in the bone marrow are killed. Some autoreactive T-cells & B-cells may escape these defense mechanisms, which is where peripheral immune tolerance defenses take action by preventing them from causing disease. However, these additional lines of defense can still fail. Further detail on immune dysregulation's contribution to MS risk is provided in the pathophysiology section of this article as well as the standalone article on the pathophysiology of 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 (EBV), 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 develop MS. The study found a 32-fold increased risk of developing MS after infection with EBV. 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 to be more likely to promote autoimmune responses in a person who also has a vitamin D deficiency. The exact nature of this relationship is poorly understood.

Genetics

HLA region of chromosome 6: Changes in this area increase the probability of getting MS.

MS is not considered a hereditary disease, but several genetic variations have been shown to increase its risk. Some of these genes appear to have higher expression levels in microglial cells than expected by chance. The probability of developing MS is higher in relatives of an affected person, with a greater risk among those more closely related. An identical twin of an affected individual has a 30% chance of developing MS, 5% for a nonidentical twin, 2.5% for a sibling, and an even lower chance for a half sibling. If both parents are affected, the risk in their children is 10 times that of the general population. MS is also more common in some ethnic groups than others.

Specific genes that have been linked with MS include differences in the human leukocyte antigen (HLA) system—a group of genes on chromosome 6 that serves as the major histocompatibility complex (MHC). The contribution of HLA variants to MS susceptibility has been known since the 1980s, and this same region has also been implicated in the development of other autoimmune diseases, such as type 1 diabetes and systemic lupus erythematosus. The most consistent finding is the association between higher risk of developing multiple sclerosis and the MHC allele DR15, which is present in 30% of the U.S. and Northern European population. Other loci exhibit a protective effect, such as HLA-C554 and HLA-DRB1*11. HLA differences account for an estimated 20 to 60% of the genetic predisposition. Genome-wide association studies have revealed at least 200 variants outside the HLA locus that affect the risk of MS.

Geography

Geographic risk distribution of MS

The prevalence of MS from a geographic standpoint resembles a gradient, with MS being more common in people who live farther from the equator (e.g. those who live in northern regions of the world), although exceptions exist. The cause of this geographical pattern is not clear, although exposure to ultraviolet B (UVB) radiation and vitamin D levels have been proposed as potential explanations. As such, those who live in northern regions of the world are thought to have less exposure to UVB radiation and subsequently lower levels of vitamin D, which is a known risk factor for developing MS. Inversely, those who live in areas of relatively higher sun exposure and subsequently increased UVB radiation have a decreased risk of developing MS. While the north–south gradient of incidence is decreasing, as of 2010, it is still present.

MS is more common in regions with northern European populations, so the geographic variation may simply reflect the global distribution of these high-risk populations.

A relationship between season of birth and MS lends support to this idea, with fewer people born in the Northern Hemisphere in November compared to May being affected later in life.

Environmental factors may play a role during childhood, with several studies finding that people who move to a different region of the world before the age of 15 acquire the new region's risk of MS. If migration takes place after age 15, the persons retain the risk of their home country. Some evidence indicates that the effect of moving may still apply to people older than 15.

There are some exceptions to the above mentioned geographic pattern. These include ethnic groups that are at low risk and that live far from the equator such as the Sami, Amerindians, Canadian Hutterites, New Zealand Māori, and Canada's Inuit, as well as groups that have a relatively high risk and that live closer to the equator such as Sardinians, inland Sicilians, Palestinians, and Parsi.

Impact of temperature

MS symptoms may increase if body temperature is dysregulated. Fatigue is particularly effected.

Other

Smoking may be an independent risk factor for MS. Stress may also be a risk factor, although the evidence to support this is weak. Association with occupational exposures and toxins—mainly organic solvents—has been evaluated, but no clear conclusions have been reached. Vaccinations were studied as causal factors; most studies, though, show no association. Several other possible risk factors, such as diet and hormone intake, have been evaluated, but evidence on their relation with the disease is "sparse and unpersuasive". Gout occurs less than would be expected and lower levels of uric acid have been found in people with MS. This has led to the theory that uric acid is protective, although its exact importance remains unknown. Obesity during adolescence and young adulthood is a risk factor for MS.

Pathophysiology

Main article: Pathophysiology of multiple sclerosis

Multiple sclerosis

Multiple sclerosis is an autoimmune disease, primarily mediated by T-cells. The three main characteristics of MS are the formation of lesions in the central nervous system (also called plaques), inflammation, and the destruction of myelin sheaths of neurons. These features interact in a complex and not yet fully understood manner to produce the breakdown of nerve tissue, and in turn, the signs and symptoms of the disease. Damage is believed to be caused, at least in part, by attack on the nervous system by a person's own immune system.

Immune dysregulation

As briefly detailed in the causes section of this article, MS is currently thought to stem from a failure of the body's immune system to kill off autoreactive T-cells & B-cells. Currently, the T-cell subpopulations that are thought to drive the development of MS are autoreactive CD8+ T-cells, CD4+ helper T-cells, and T_H17 cells. These autoreactive T-cells produce substances called cytokines that induce an inflammatory immune response in the CNS, leading to the development of the disease. More recently, however, the role of autoreactive B-cells has been elucidated. Evidence of their contribution to the development of MS is implicated through the presence of oligoclonal IgG bands (antibodies produced by B-cells) in the CSF of patients with MS. The presence of these oligoclonal bands has been used as supportive evidence in clinching a diagnosis of MS. As similarly described before, B-cells can also produce cytokines that induce an inflammatory immune response via activation of autoreactive T-cells. As such, higher levels of these autoreactive B-cells is associated with increased number of lesions & neurodegeneration as well as worse disability.

Another cell population that is becoming increasingly implicated in MS are microglia. These cells are resident to & keep watch over the CNS, responding to pathogens by shifting between pro- & anti-inflammatory states. Microglia have been shown to be involved in the formation of MS lesions and have been shown to be involved in other diseases that primarily affect the CNS white matter. Although, because of their ability to switch between pro- & anti-inflammatory states, microglia have also been shown to be able to assist in remyelination & subsequent neuron repair. As such, microglia are thought to be participating in both acute & chronic MS lesions, with 40% of phagocytic cells in early active MS lesions being proinflammatory microglia.

Lesions

Demyelination in MS: On Klüver-Barrera myelin staining, decoloration in the area of the lesion can be appreciated.

The name multiple sclerosis refers to the scars (sclerae – better known as plaques or lesions) that form in the nervous system. These lesions most commonly affect the white matter in the optic nerve, brain stem, basal ganglia, and spinal cord, or white matter tracts close to the lateral ventricles. The function of white matter cells is to carry signals between grey matter areas, where the processing is done, and the rest of the body. The peripheral nervous system is rarely involved.

MRI machine used as a tool for MS diagnosis

To be specific, MS involves the loss of oligodendrocytes, the cells responsible for creating and maintaining a fatty layer—known as the myelin sheath—which helps the neurons carry electrical signals (action potentials). This results in a thinning or complete loss of myelin, and as the disease advances, the breakdown of the axons of neurons. When the myelin is lost, a neuron can no longer effectively conduct electrical signals. A repair process, called remyelination, takes place in early phases of the disease, but the oligodendrocytes are unable to completely rebuild the cell's myelin sheath. Repeated attacks lead to successively less effective remyelinations, until a scar-like plaque is built up around the damaged axons. These scars are the origin of the symptoms and during an attack magnetic resonance imaging (MRI) often shows more than 10 new plaques. This could indicate that some number of lesions exist, below which the brain is capable of repairing itself without producing noticeable consequences. Another process involved in the creation of lesions is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons. A number of lesion patterns have been described.

Inflammation

Apart from demyelination, the other sign of the disease is inflammation. Fitting with an immunological explanation, the inflammatory process is caused by T cells, a kind of lymphocytes that plays an important role in the body's defenses. T cells gain entry into the brain as a result of disruptions in the blood–brain barrier. The T cells recognize myelin as foreign and attack it, explaining why these cells are also called "autoreactive lymphocytes".

The attack on myelin starts inflammatory processes, which trigger other immune cells and the release of soluble factors like cytokines and antibodies. A further breakdown of the blood-brain barrier, in turn, causes a number of other damaging effects, such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins. Inflammation can potentially reduce transmission of information between neurons in at least three ways. The soluble factors released might stop neurotransmission by intact neurons. These factors could lead to or enhance the loss of myelin, or they may cause the axon to break down completely.

Blood–brain barrier

The blood–brain barrier (BBB) is a part of the capillary system that prevents the entry of T cells into the central nervous system. It may become permeable to these types of cells secondary to an infection by a virus or bacteria. After it repairs itself, typically once the infection has cleared, T cells may remain trapped inside the brain. Gadolinium cannot cross a normal BBB, so gadolinium-enhanced MRI is used to show BBB breakdowns.

MS fatigue

The pathophysiology and mechanisms causing MS fatigue are not well understood. MS fatigue can be affected by body heat, and this may differentiate MS fatigue from other primary fatigue. Fatigability (loss of strength) may increase perception of fatigue, but the two measures warrant independent assessment in clinical studies.

Diagnosis

Main article: Multiple sclerosis diagnosis

Animation showing dissemination of brain lesions in time and space as demonstrated by monthly MRI studies along a year

Multiple sclerosis as seen on MRI

Multiple sclerosis is typically diagnosed based on the presenting signs and symptoms, in combination with supporting medical imaging and laboratory testing. It can be difficult to confirm, especially early on, since the signs and symptoms may be similar to those of other medical problems.

McDonald criteria

The McDonald criteria, which focus on clinical, laboratory, and radiologic evidence of lesions at different times and in different areas, is the most commonly used method of diagnosis with the Schumacher and Poser criteria being of mostly historical significance. The McDonald criteria states that patients with multiple sclerosis should have lesions which are disseminated in time (DIT) and disseminated in space (DIS), i.e. lesions which have appeared in different areas in the brain and at different times. Below is an abbreviated outline of the 2017 McDonald Criteria for diagnosis of MS.

• At least 2 clinical attacks with MRI showing 2 or more lesions characteristic of MS.
• At least 2 clinical attacks with MRI showing 1 lesion characteristic of MS with clear historical evidence of a previous attack involving a lesion at a distinct location in the CNS.
• At least 2 clinical attacks with MRI showing 1 lesion characteristic of MS, with DIT established by an additional clinical attack at a distinct CNS site or by MRI showing an old MS lesion.
• 1 clinical attack with MRI showing at least 2 lesions characteristic of MS, with DIT established by an additional attack, by MRI showing old MS lesion(s), or presence of oligoclonal bands in CSF.
• 1 clinical attack with MRI showing 1 lesion characteristic of MS, with DIS established by an additional attack at a different CNS site or by MRI showing old MS lesion(s), and DIT established by an additional attack, by MRI showing old MS lesion(s), or presence of oligoclonal bands in CSF.

As of 2017, no single test (including biopsy) can provide a definitive diagnosis.

MRI

Magnetic resonance imaging (MRI) of the brain and spine may show areas of demyelination (lesions or plaques). Gadolinium can be administered intravenously as a contrast agent to highlight active plaques, and by elimination, demonstrate the existence of historical lesions not associated with symptoms at the moment of the evaluation.

Central vein signs (CVSs) have been proposed as a good indicator of MS in comparison with other conditions causing white lesions. One small study found fewer CVSs in older and hypertensive people. Further research on CVS as a biomarker for MS is ongoing.

Cerebrospinal fluid (lumbar puncture)

Testing of cerebrospinal fluid obtained from a lumbar puncture can provide evidence of chronic inflammation in the central nervous system. The cerebrospinal fluid is tested for oligoclonal bands of IgG on electrophoresis, which are inflammation markers found in 75–85% of people with MS.

Differential diagnosis

Several diseases present similarly to MS. Medical professionals use a patient's specific presentation, history, and exam findings to make an individualized differential. Red flags are findings that suggest an alternate diagnosis, although they do not rule out MS. Red flags include a patient younger than 15 or older than 60, less than 24 hours of symptoms, involvement of multiple cranial nerves, involvement of organs outside of the nervous system, and atypical lab and exam findings.

In an emergency setting, it is important to rule out a stroke or bleeding in the brain. Intractable vomiting, severe optic neuritis, or bilateral optic neuritis raises suspicion for neuromyelitis optica spectrum disorder (NMOSD). Infectious diseases that may look similar to multiple sclerosis include HIV, Lyme disease, and syphilis. Autoimmune diseases include neurosarcoidosis, lupus, Guillain-Barré syndrome, acute disseminated encephalomyelitis, and Behçet's disease. Psychiatric conditions such as anxiety or conversion disorder may also present in a similar way. Other rare diseases on the differential include CNS lymphoma, congenital leukodystrophies, and anti-MOG-associated myelitis.

Types and variants

MS progression types. From bottom to top: RRMS, PPMS, SPMS.

Several phenotypes (commonly termed "types"), or patterns of progression, have been described. Phenotypes use the past course of the disease in an attempt to predict the future course. They are important not only for prognosis, but also for treatment decisions.

The International Advisory Committee on Clinical Trials of MS describes four types of MS (revised in 2013) in what is known as the Lublin classification:

1. Clinically isolated syndrome (CIS)
2. Relapsing-remitting MS (RRMS)
3. Primary progressive MS (PPMS)
4. Secondary progressive MS (SPMS)

CIS can be characterised as a single lesion seen on MRI which is associated with signs or symptoms found in MS. Due to the McDonald criteria, it does not completely fit the criteria to be diagnosed as MS, hence being named "clinically isolated syndrome". CIS can be seen as the first episode of demyelination in the central nervous system. To be classified as CIS, the attack must last at least 24 hours and be caused by inflammation or demyelination of the central nervous system. Patients who suffer from CIS may or may not go on to develop MS, but 30 to 70% of persons who experience CIS will later develop MS.

RRMS is characterized by unpredictable relapses followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. Deficits that occur during attacks may either resolve or leave problems, the latter in about 40% of attacks and being more common the longer a person has had the disease. This describes the initial course of 80% of individuals with MS.

PPMS occurs in roughly 10–20% of individuals with the disease, with no remission after the initial symptoms. It is characterized by progression of disability from onset, with no, or only occasional and minor, remissions and improvements. The usual age of onset for the primary progressive subtype is later than of the relapsing-remitting subtype. It is similar to the age that secondary progressive usually begins in RRMS, around 40 years of age.

SPMS occurs in around 65% of those with initial RRMS, who eventually have progressive neurologic decline between acute attacks without any definite periods of remission. Occasional relapses and minor remissions may appear. The most common length of time between disease onset and conversion from RRMS to SPMS is 19 years.

Special courses

Independently of the types published by the MS associations, regulatory agencies such as the FDA often consider special courses, trying to reflect some clinical trials results on their approval documents. Some examples could be "highly active MS" (HAMS), "active secondary MS" (similar to the old progressive-relapsing) and "rapidly progressing PPMS".

Also, deficits always resolving between attacks is sometimes referred to as "benign" MS, although people still build up some degree of disability in the long term. On the other hand, the term malignant multiple sclerosis is used to describe people with MS having reached significant level of disability in a short period.

An international panel has published a standardized definition for the course HAMS.

Variants

Atypical variants of MS have been described; these include tumefactive multiple sclerosis, Balo concentric sclerosis, Schilder's diffuse sclerosis, and Marburg multiple sclerosis. Debate remains on whether they are MS variants or different diseases. Some diseases previously considered MS variants, such as Devic's disease, are now considered outside the MS spectrum.

Management

Main article: Management of multiple sclerosis

Although no cure for multiple sclerosis has been found, several therapies have proven helpful. Several effective treatments can decrease the number of attacks and the rate of progression. The primary aims of therapy are returning function after an attack, preventing new attacks, and preventing disability. Starting medications is generally recommended in people after the first attack when more than two lesions are seen on MRI.

The first approved medications used to treat MS were modestly effective, though were poorly tolerated and had many adverse effects. Several treatment options with better safety and tolerability profiles have been introduced, improving the prognosis of MS.

As with any medical treatment, medications used in the management of MS have several adverse effects. Alternative treatments are pursued by some people, despite the shortage of supporting evidence of efficacy.

Initial management of acute flare

During symptomatic attacks, administration of high doses of intravenous corticosteroids, such as methylprednisolone, is the usual therapy, with oral corticosteroids seeming to have a similar efficacy and safety profile. Although effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery. The long-term benefit is unclear in optic neuritis as of 2020. The consequences of severe attacks that do not respond to corticosteroids might be treatable by plasmapheresis.

Chronic management

Relapsing remitting multiple sclerosis

Multiple disease-modifying medications were approved by regulatory agencies for RRMS; they are modestly effective at decreasing the number of attacks. Interferons and glatiramer acetate are first-line treatments and are roughly equivalent, reducing relapses by approximately 30%. Early-initiated long-term therapy is safe and improves outcomes.

Treatment of CIS with interferons decreases the chance of progressing to clinical MS. Efficacy of interferons and glatiramer acetate in children has been estimated to be roughly equivalent to that of adults. The role of some newer agents such as fingolimod, teriflunomide, and dimethyl fumarate, is not yet entirely clear. Making firm conclusions about the best treatment is difficult, especially regarding the long‐term benefit and safety of early treatment, given the lack of studies directly comparing disease-modifying therapies or long-term monitoring of patient outcomes.

The relative effectiveness of different treatments is unclear, as most have only been compared to placebo or a small number of other therapies. Direct comparisons of interferons and glatiramer acetate indicate similar effects or only small differences in effects on relapse rate, disease progression, and MRI measures. There is high confidence that natalizumab, cladribine, or alemtuzumab are decreasing relapses over a period of two years for people with RRMS. Natalizumab and interferon beta-1a (Rebif) may reduce relapses compared to both placebo and interferon beta-1a (Avonex) while Interferon beta-1b (Betaseron), glatiramer acetate, and mitoxantrone may also prevent relapses. Evidence on relative effectiveness in reducing disability progression is unclear. There is moderate confidence that a two-year treatment with natalizumab slows disability progression for people with RRMS. All medications are associated with adverse effects that may influence their risk to benefit profiles.

Ublituximab was approved for medical use in the United States in December 2022.

Medications

Overview of medications available for MS.

Medication	Compound	Producer	Use	Efficacy (annualized relapse reduction rate)	Annualized relapse rate (ARR)
Avonex	Interferon beta-1a	Biogen	Intramuscular	30%	0.25
Rebif	Interferon beta-1a	Merck Serono	Subcutaneous	30%	0.256
Extavia	Interferon beta-1b	Bayer Schering	Subcutaneous	30%	0.256
Copaxone	Glatiramer acetate	Teva Pharmaceuticals	Subcutaneous	30%	0.3
Aubagio	Teriflunomide	Genzyme	Oral	30%	0.35
Plegridy	Interferon beta-1a	Biogen	Subcutaneous	30%	0.12
Tecfidera	Dimethyl fumarate	Biogen	Oral	50%	0.15
Vumerity	Diroximel fumarate	Biogen	Oral	50%	0.11-0.15
Gilenya	Fingolimod		Oral	50%	0.22-0.25
Zeposia	Ozanimod		Oral		0.18-0.24
Kesimpta	Ofatumumab		Subcutaneous	70%	0.09-0.14
Mavenclad	Cladribine		Oral	70%	0.1-0.14
Lemtrada	Alemtuzumab		Intravenous	70%	0.08
Ocrevus	Ocrelizumab		Intravenous	70%	0.09

Progressive multiple sclerosis

In 2011, mitoxantrone was the first medication approved for secondary progressive MS. In this population, tentative evidence supports mitoxantrone moderately slowing the progression of the disease and decreasing rates of relapses over two years.

New approved medications continue to emerge in modern medicine. In March 2017, the FDA approved ocrelizumab as a treatment for primary progressive MS in adults, the first drug to gain that approval, with requirements for several Phase IV clinical trials. It is also used for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults. According to a 2021 Cochrane review, ocrelizumab may reduce worsening of symptoms for primary progressive MS and probably increases unwanted effects but makes little or no difference to the number of serious unwanted effects.

In 2019, siponimod and cladribine were approved in the United States for the treatment of secondary progressive multiple sclerosis (SPMS). Subsequently, ozanimod was approved in 2020, and ponesimod was approved in 2021, which were both approved for management of CIS, relapsing MS, and SPMS in the U.S., and RRMS in Europe.

Adverse effects

Irritation zone after injection of glatiramer acetate

The disease-modifying treatments have several adverse effects. One of the most common is irritation at the injection site for glatiramer acetate and the interferons (up to 90% with subcutaneous injections and 33% with intramuscular injections). Over time, a visible dent at the injection site, due to the local destruction of fat tissue, known as lipoatrophy, may develop. Interferons may produce flu-like symptoms; some people taking glatiramer experience a post-injection reaction with flushing, chest tightness, heart palpitations, and anxiety, which usually lasts less than thirty minutes. More dangerous but much less common are liver damage from interferons, systolic dysfunction (12%), infertility, and acute myeloid leukemia (0.8%) from mitoxantrone, and progressive multifocal leukoencephalopathy occurring with natalizumab (occurring in 1 in 600 people treated).

Fingolimod may give rise to hypertension and slowed heart rate, macular edema, elevated liver enzymes, or a reduction in lymphocyte levels. Tentative evidence supports the short-term safety of teriflunomide, with common side effects including: headaches, fatigue, nausea, hair loss, and limb pain. There have also been reports of liver failure and PML with its use and it is dangerous for fetal development. Most common side effects of dimethyl fumarate are flushing and gastrointestinal problems. While dimethyl fumarate may lead to a reduction in the white blood cell count there were no reported cases of opportunistic infections during trials.

Associated symptoms

Both medications and neurorehabilitation have been shown to improve some symptoms, though neither changes the course of the disease. Some symptoms have a good response to medication, such as bladder spasticity, while others are little changed. Equipment such as catheters for neurogenic bladder dysfunction or mobility aids can be helpful in improving functional status.

A multidisciplinary approach is important for improving quality of life; however, it is difficult to specify a 'core team' as many health services may be needed at different points in time. Multidisciplinary rehabilitation programs increase activity and participation of people with MS but do not influence impairment level. Studies investigating information provision in support of patient understanding and participation suggest that while interventions (written information, decision aids, coaching, educational programmes) may increase knowledge, the evidence of an effect on decision making and quality of life is mixed and low certainty. There is limited evidence for the overall efficacy of individual therapeutic disciplines, though there is good evidence that specific approaches, such as exercise, and psychological therapies are effective. Cognitive training, alone or combined with other neuropsychological interventions, may show positive effects for memory and attention though firm conclusions are not possible given small sample numbers, variable methodology, interventions and outcome measures. The effectiveness of palliative approaches in addition to standard care is uncertain, due to lack of evidence. The effectiveness of interventions, including exercise, specifically for the prevention of falls in people with MS is uncertain, while there is some evidence of an effect on balance function and mobility. Cognitive behavioral therapy has shown to be moderately effective for reducing MS fatigue. The evidence for the effectiveness of non-pharmacological interventions for chronic pain is insufficient to recommend such interventions alone, however their use in combination with medications may be reasonable.

Non-pharmaceutical

There is some evidence that aquatic therapy is a beneficial intervention.

The spasticity associated with MS can be difficult to manage because of the progressive and fluctuating course of the disease. Although there is no firm conclusion on the efficacy in reducing spasticity, PT interventions can be a safe and beneficial option for patients with multiple sclerosis. Physical therapy including vibration interventions, electrical stimulation, exercise therapy, standing therapy, and radial shock wave therapy (RSWT), were beneficial for limiting spasticity, helping limit excitability, or increasing range of motion.

Alternative treatments

Over 50% of people with MS may use complementary and alternative medicine, although percentages vary depending on how alternative medicine is defined. Regarding the characteristics of users, they are more frequently women, have had MS for a longer time, tend to be more disabled and have lower levels of satisfaction with conventional healthcare. The evidence for the effectiveness for such treatments in most cases is weak or absent. Treatments of unproven benefit used by people with MS include dietary supplementation and regimens, vitamin D, relaxation techniques such as yoga, herbal medicine (including medical cannabis), hyperbaric oxygen therapy, self-infection with hookworms, reflexology, acupuncture, and mindfulness. Evidence suggests vitamin D supplementation, irrespective of the form and dose, provides no benefit for people with MS; this includes for measures such as relapse recurrence, disability, and MRI lesions while effects on health‐related quality of life and fatigue are unclear. There is insufficient evidence supporting high-dose biotin and some evidence for increased disease activity and higher risk of relapse with its use. A recent review of the effectiveness of Cannabis and Cannabinoids (2022) found that compared with placebo nabiximols probably reduce the severity of spasticity in the short term.

Prognosis

The availability of treatments that modify the course of multiple sclerosis beginning in the 1990s, known as disease-modifying therapies (DMTs), has improved prognosis. These treatments can reduce relapses and slow progression, but there is no cure.

The prognosis of MS depends on the subtype of the disease, and there is considerable individual variation in the progression of the disease. In relapsing MS, the most common subtype, a 2016 cohort study found that after a median of 16.8 years from onset, one in ten needed a walking aid, and almost two in ten transitioned to secondary progressive MS, a form characterized by more progressive decline. With treatments available in the 2020s, relapses can be eliminated or substantially reduced. However, "silent progression" of the disease still occurs.

In addition to secondary progressive MS (SPMS), a small proportion of people with MS (10–15%) experience progressive decline from the onset, known as primary progressive MS (PPMS). Most treatments have been approved for use in relapsing MS; there are fewer treatments with lower efficacy for progressive forms of MS. The prognosis for progressive MS is worse, with faster accumulation of disability, though with considerable individual variation. In untreated PPMS, the median time from onset to requiring a walking aid is estimated as seven years. In SPMS, a 2014 cohort study reported that people required a walking aid after an average of five years from onset of SPMS, and were chair or bed-bound after an average of fifteen years.

After diagnosis of MS, characteristics that predict a worse course are male sex, older age, and greater disability at the time of diagnosis; female sex is associated with a higher relapse rate. Currently, no biomarker can accurately predict disease progression in every patient. Spinal cord lesions, abnormalities on MRI, and more brain atrophy are predictive of a worse course, though brain atrophy as a predictor of disease course is experimental and not used in clinical practice. Early treatment leads to a better prognosis, but a higher relapse frequency when treated with DMTs is associated with a poorer prognosis. A 60-year longitudinal population study conducted in Norway found that those with MS had a life expectancy seven years shorter than the general population. Median life expectancy for RRMS patients was 77.8 years and 71.4 years for PPMS, compared to 81.8 years for the general population. Life expectancy for men was five years shorter than for women.

Эпидемиология

Смертность от рассеянного склероза на миллион человек в 2012 г.

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Рассеянный склероз является наиболее распространенным аутоиммунным заболеванием центральной нервной системы. По последним оценкам, общее число людей с рассеянным склерозом во всем мире составило 2,8 миллиона, а распространенность — 36 на 100 000 человек. Более того, распространенность широко варьируется в разных регионах мира. В Африке у пяти человек на 100 000 диагностирован рассеянный склероз, по сравнению с Юго-Восточной Азией, где распространенность составляет девять на 100 000, 112 на 100 000 в Америке и 133 на 100 000 в Европе.

Рост заболеваемости рассеянным склерозом можно объяснить просто улучшением диагностики. Исследования популяционных и географических особенностей были обычным явлением. и привели к появлению ряда теорий о причине.

РС обычно появляется у взрослых в возрасте от двадцати до тридцати лет, но редко может начаться в детстве и после 50 лет. Первичный прогрессирующий подтип чаще встречается у людей старше пятидесяти лет. Подобно многим аутоиммунным заболеваниям, это заболевание чаще встречается у женщин, и эта тенденция может усиливаться. По состоянию на 2020 год во всем мире это заболевание встречается примерно в два раза чаще у женщин, чем у мужчин, а соотношение женщин и мужчин с РС в некоторых странах достигает 4:1. У детей заболевание встречается даже чаще у женщин, чем у мужчин. в то время как у людей старше пятидесяти лет оно поражает почти одинаково мужчин и женщин.

История

Медицинское открытие

Фрагмент рисунка Карсвелла поражений рассеянного склероза в стволе головного мозга и спинном мозге (1838 г.)

Роберт Карсуэлл (1793–1857), британский профессор патологии , и Жан Крювейье (1791–1873), французский профессор патологической анатомии, описали и проиллюстрировали многие клинические детали заболевания, но не выделили его как отдельное заболевание. В частности, Карсвелл описал обнаруженные им травмы как «заметное поражение спинного мозга, сопровождающееся атрофией». Под микроскопом швейцарский патолог Георг Эдуард Риндфляйш (1836–1908) заметил в 1863 году, что связанные с воспалением поражения распределяются вокруг кровеносных сосудов.

Французский невролог Жан-Мартен Шарко (1825–1893) был первым человеком, который в 1868 году признал рассеянный склероз отдельным заболеванием. Обобщая предыдущие сообщения и добавляя собственные клинические и патологические наблюдения, Шарко назвал болезнь склерозом и бляшками .

История диагноза

Первая попытка установить набор диагностических критериев была также сделана Шарко в 1868 году. Он опубликовал то, что сейчас известно как « Триада Шарко », состоящая из нистагма, интенционного тремора и телеграфной речи (сканирующей речи). Шарко также наблюдал изменения в познании, описывая своих пациентов как имеющих «выраженное ослабление памяти» и «концепции, которые формируются медленно».

Диагностика основывалась на триаде Шарко и клинических наблюдениях до тех пор, пока Шумахер не предпринял первую попытку стандартизировать критерии в 1965 году, введя некоторые фундаментальные требования: распространение поражений во времени (DIT) и пространстве (DIS), а также то, что «признаки и симптомы не могут быть объяснены». лучше от другого болезненного процесса». Требование DIT и DIS позже было унаследовано критериями Позера и Макдональда, редакция которых используется в 2017 году.

В течение 20-го века были разработаны теории о причине и патогенезе, а в 1990-х годах начали появляться эффективные методы лечения. С начала XXI века произошли уточнения концепций. Пересмотр критериев Макдональда в 2010 году позволил диагностировать рассеянный склероз только с одним доказанным поражением (CIS).

В 1996 году Национальное общество рассеянного склероза США (NMSS) (Консультативный комитет по клиническим испытаниям) определило первую используемую версию клинических фенотипов. В этой первой версии они предоставили стандартизированные определения для четырех клинических курсов рассеянного склероза: рецидивно-ремиттирующего (РР), вторично-прогрессирующего (СП), первично-прогрессирующего (ПП) и прогрессивно-рецидивирующего (ПР). В 2010 году PR был упразднен и в него была включена компания CIS. Три года спустя пересмотр «Фенотипов течения заболевания» 2013 г. был вынужден рассматривать CIS как один из фенотипов рассеянного склероза, сделав устаревшими некоторые выражения, такие как «конверсия из CIS в MS». Другие организации позже предложили новые клинические фенотипы, такие как HAMS (высоко активный РС).

Исторические случаи

Фотографическое исследование передвижения женщины с рассеянным склерозом и трудностями при ходьбе, созданное в 1887 году Мейбриджем .

Существует несколько исторических свидетельств о людях, которые, вероятно, болели рассеянным склерозом и жили до или вскоре после того, как болезнь была описана Шарко.

Молодая женщина по имени Халлдора, жившая в Исландии около 1200 года, внезапно потеряла зрение и подвижность, но через семь дней восстановила их. Святая Лидвина Схидамская . (1380–1433), голландская монахиня , может быть одной из первых четко идентифицируемых людей с рассеянным склерозом С 16 лет и до своей смерти в 53 года у нее были периодические боли, слабость ног и потеря зрения: симптомы, типичные для рассеянного склероза. Оба случая привели к выдвижению гипотезы о «гене викингов» для распространения заболевания.

Август Фредерик д'Эсте (1794–1848), сын принца Августа Фредерика, герцога Сассекского и леди Августы Мюррей и внук Георга III Соединенного Королевства , почти наверняка страдал рассеянным склерозом. Д'Эсте оставил подробный дневник, в котором описал свои 22 года жизни с этой болезнью. Его дневник начался в 1822 году и закончился в 1846 году, хотя он оставался неизвестным до 1948 года. Его симптомы начались в 28 лет с внезапной временной потери зрения ( amaurosis fugax ) после похорон друга. Во время болезни у него появилась слабость ног, неуклюжесть рук, онемение, головокружение, нарушение мочеиспускания и эректильная дисфункция . В 1844 году он начал пользоваться инвалидной коляской. Несмотря на болезнь, он сохранял оптимистический взгляд на жизнь. Еще один ранний отчет о рассеянном склерозе вёл британский дневник WNP Барбеллион , псевдоним Брюса Фредерика Каммингса (1889–1919), который вел подробный журнал своего диагноза и борьбы. Его дневник был опубликован в 1919 году под названием «Журнал разочарованного человека» . Чарльз Диккенс , проницательный наблюдатель, описал возможный двусторонний неврит зрительного нерва со сниженным контрастным зрением и феномен Утхоффа у главной женской героини «Холодного дома» (1852–1853), Эстер Саммервилл.

Исследовать

Основная статья: Исследования рассеянного склероза

Вирус Эпштейна-Барра

патогенез рассеянного склероза, связанный с вирусом Эпштейна-Барр (ВЭБ) По состоянию на 2022 год активно исследуется , а также методы лечения, модифицирующие заболевание; Требуется понимание того, как факторы риска сочетаются с ВЭБ, вызывая РС. Будет ли ВЭБ единственной причиной рассеянного склероза, можно будет лучше понять, если будет разработана вакцина против ВЭБ и показано, что она также предотвращает рассеянный склероз.

Несмотря на то, что различные исследования показали связь между инфекцией EBV и последующим развитием рассеянного склероза, механизмы этой корреляции не совсем ясны, и было предложено несколько теорий, объясняющих взаимосвязь между двумя заболеваниями. Считается, что вовлечение EBV-инфицированных B-клеток (B-лимфоцитов) а участие антител против EBNA , которых, по-видимому, значительно больше у пациентов с рассеянным склерозом, играет решающую роль в развитии заболевания. Это подтверждается тем фактом, что лечение против В-клеток, например, окрелизумаб , уменьшает симптомы рассеянного склероза: ежегодные рецидивы возникают реже и прогрессирование инвалидности происходит медленнее. 2022 года Исследование Стэнфордского университета показало, что во время инфекции ВЭБ может возникнуть молекулярная мимикрия, при которой иммунная система будет вырабатывать антитела против белка EBNA 1, который в то же время способен связываться с GlialCAM в миелине. Кроме того, они наблюдали явление, которое редко встречается у здоровых людей, но часто обнаруживается у пациентов с рассеянным склерозом: B-клетки перемещаются в головной и спинной мозг, где они производят полосы олигоклональных антител. Большинство этих олигоклональных полос действительно имеют сродство к вирусному белку EBNA1, который перекрестно реагирует с GlialCAM. Эти антитела присутствуют в большом количестве примерно у 20–25% пациентов с рассеянным склерозом и ухудшают аутоиммунную демиелинизацию, что, как следствие, приводит к патофизиологическому обострению заболевания. Более того, интратекальная олигоклональная экспансия с постоянной соматической гипермутацией уникальна при рассеянном склерозе по сравнению с другими нейровоспалительными заболеваниями. В ходе исследования также было измерено количество антител с генами IGHV 3–7, что, по-видимому, связано с прогрессированием заболевания. Антитела на основе IGHV3–7 связываются с высоким сродством к EBNA1 и GlialCAM. В этом процессе активно процветает демиелинизация. Вполне вероятно, что B-клетки, экспрессирующие гены IGHV 3–7, проникли в спинномозговую жидкость и подверглись созреванию аффинности после контакта с GlialCAM, что, как следствие, привело к выработке высокоаффинных антител против GlialCAM. Это было дополнительно показано на мышиной модели EAE, где иммунизация EBNA1 приводила к сильному ответу B-клеток против GlialCAM, что ухудшало EAE.

Эндогенные ретровирусы человека

Два члена семейства эндогенных ретровирусов-W человека ( HERV -W), а именно ERVWE1 и ретровирус, ассоциированный с рассеянным склерозом (MSRV), могут быть кофакторами иммунопатогенеза рассеянного склероза. HERV составляют до 8% генома человека; большинство из них эпигенетически молчат, но могут быть реактивированы экзогенными вирусами, провоспалительными состояниями или окислительным стрессом.

Лекарства

Лекарства, влияющие на потенциалзависимые натриевые ионные каналы, исследуются в качестве потенциальной нейропротекторной стратегии из-за предполагаемой роли натрия в патологическом процессе, приводящем к повреждению аксонов и накапливающейся инвалидности. Недостаточно доказательств эффективности блокаторов натриевых каналов у людей с рассеянным склерозом.

Патогенез

Рассеянный склероз представляет собой клинически определяемое заболевание с несколькими атипичными проявлениями. Некоторые аутоантитела были обнаружены в атипичных случаях рассеянного склероза, что привело к появлению отдельных семейств заболеваний и ограничило ранее более широкую концепцию рассеянного склероза.

Аутоантитела к AQP4 были обнаружены при оптикомиелите (НМО), который ранее считался вариантом рассеянного склероза. Был принят спектр заболеваний, названных NMOSD (болезни спектра NMO) или заболевания анти-AQP4. В некоторых случаях рассеянного склероза наблюдались аутоантитела против MOG , в основном перекрывающиеся с вариантом Марбурга. Было обнаружено, что аутоантитела против MOG также присутствуют при ADEM, и рассматривается второй спектр отдельных заболеваний. Этот спектр у разных авторов назван по-разному, но обычно он чем-то похож на демиелинизирующие заболевания, вызванные анти-MOG .

Принимается третий вид аутоантител. Это несколько аутоантител к нейрофасцину , которые повреждают узлы Ранвье нейронов. Эти антитела больше связаны с демиелинизацией периферической нервной системы, но они также были обнаружены при хроническом прогрессирующем ППРС и комбинированной центральной и периферической демиелинизации (CCPD, который считается еще одним атипичным проявлением рассеянного склероза).

В дополнение к значимости аутоантител при рассеянном склерозе сообщалось о четырех различных моделях демиелинизации, что открывает возможность рассматривать рассеянный склероз как гетерогенное заболевание .

Биомаркеры

Основная статья: Биомаркеры рассеянного склероза

МРТ- сканирование головного мозга, выполненное с использованием фазовой последовательности градиентного эха, показывающее отложения железа в очаге поражения белого вещества (внутри зеленого прямоугольника в середине изображения; увеличено и отмечено красной стрелкой в ​​верхнем левом углу)

Поскольку прогрессирование заболевания является результатом дегенерации нейронов, роль белков, вызывающих потерю нервной ткани, таких как нейрофиламенты , тау и N-ацетиласпартат, находится в стадии изучения.

Совершенствование методов нейровизуализации, таких как позитронно-эмиссионная томография (ПЭТ) или МРТ, обещает улучшить диагностику и прогнозирование прогноза. Что касается МРТ, то существует несколько методов, которые уже показали некоторую полезность в исследовательских целях и могут быть внедрены в клиническую практику, такие как последовательности восстановления двойной инверсии, перенос намагниченности , тензор диффузии и функциональная магнитно-резонансная томография . Эти методы более специфичны для заболевания, чем существующие, но им все еще не хватает некоторой стандартизации протоколов сбора данных и создания нормативных значений. Это особенно справедливо для протонной магнитно-резонансной спектроскопии , для которой ряд методологических различий, наблюдаемых в литературе, может лежать в основе продолжающихся несоответствий в метаболических нарушениях центральной нервной системы, особенно в отношении N-ацетиласпартата , миоинозитола , холина , глутамата , ГАМК и GSH. , наблюдаемый при рассеянном склерозе и его подтипах. В стадии разработки находятся и другие методы, включающие контрастные вещества, способные измерять уровни периферических макрофагов , воспаления или дисфункции нейронов. и методы измерения отложения железа, которые могут помочь определить роль этого признака при рассеянном склерозе или перфузии головного мозга.

COVID-19

Было обнаружено, что уровень госпитализации выше среди лиц с рассеянным склерозом и инфекцией COVID-19 - 10%, тогда как общий уровень инфицирования оценивается в 4%. Общая распространенность смертности среди госпитализированных лиц с рассеянным склерозом оценивается в 4%.

Метформин

Исследование 2019 года на крысах и исследование 2024 года на мышах показали, что препарат первой линии для лечения диабета 2 типа , метформин , может способствовать ремиелинизации . Многообещающий препарат в настоящее время исследуется на людях в рамках многоэтапных испытаний Octopus, направленных на тестирование существующих лекарств для лечения других заболеваний у пациентов с рассеянным склерозом. продолжаются клинические испытания на людях В настоящее время в Бельгии для пациентов с неактивным прогрессирующим рассеянным склерозом. в Великобритании в сочетании с клемастином для лечения рецидивирующего ремиттирующего рассеянного склероза, и Канада — для пациентов с рассеянным склерозом до 25 лет.

Другие новые теории

Одна из новых гипотез, называемая гигиенической гипотезой, предполагает, что воздействие инфекционных агентов в раннем возрасте помогает развивать иммунную систему и снижает восприимчивость к аллергиям и аутоиммунным расстройствам. Гигиеническая гипотеза связана с гипотезами рассеянного склероза и микробиома .

Также было высказано предположение, что некоторые бактерии, обнаруженные в кишечнике, используют молекулярную мимикрию для проникновения в мозг через ось кишечник-мозг , инициируя воспалительную реакцию и увеличивая проницаемость гематоэнцефалического барьера. Уровни витамина D также коррелируют с рассеянным склерозом; более низкие уровни витамина D соответствуют повышенному риску рассеянного склероза, что позволяет предположить меньшую распространенность в тропиках – регионах с более богатым витамином D солнечным светом – что усиливает влияние географического положения на развитие рассеянного склероза. Механизмы рассеянного склероза начинаются, когда периферические аутореактивные эффекторные CD4+ Т-клетки активируются и перемещаются в ЦНС. Антигенпрезентирующие клетки локализуют реактивацию аутореактивных эффекторных CD4-Т-клеток после их проникновения в ЦНС, привлекая больше Т-клеток и макрофагов для формирования воспалительного поражения. У пациентов с рассеянным склерозом макрофаги и микроглия собираются в местах, где активно происходят демиелинизация и нейродегенерация, а активация микроглии более очевидна в нормально выглядящем белом веществе пациентов с рассеянным склерозом. Астроциты производят нейротоксичные химические вещества, такие как оксид азота и TNFα , привлекают нейротоксичные воспалительные моноциты в ЦНС и ответственны за астроглиоз — рубцевание, которое предотвращает распространение нейровоспаления и убивает нейроны внутри рубцовой области.

В 2024 году учёные поделились исследованиями своих выводов о древней миграции в Северную Европу из Ямного ареала культуры , отслеживание вариантов генов риска рассеянного склероза, датируемых примерно 5000 лет назад. Варианты гена риска рассеянного склероза защищали древних скотоводов от болезней животных, но современный образ жизни, диеты и лучшая гигиена позволили этому гену развиваться, что сегодня приводит к более высокому риску развития рассеянного склероза.

См. также

• Список организаций, занимающихся рассеянным склерозом
• Список людей с рассеянным склерозом

Внешние ссылки

• Рассеянный склероз в Керли