BY: SAI MANOGNA (MSIWM014)
Multiple sclerosis (MS) is an inflammatory immune-mediated disorder that targets myelinated axons in the central nervous system, kills myelin and axon to various degrees and causes severe physical impairment in more than 30 % of patients within 20-25 years.
In most cases, with short-term episodes of neurological deficits that resolve entirely, the disorder follows a relapsing-remitting pattern. A minority of patients experiences the steadily progressive neurologic decline.
The cause of MS is unclear, but it is likely to include a combination of genetic susceptibility and a suspected nongenetic trigger (e.g., viral infection, low levels of vitamin D) leading to a self-sustaining autoimmune condition resulting in repeated CNS immune attacks. A common misconception is that any CNS demyelination attack indicates a diagnosis of acute MS. If a patient has a first demyelination attack, the doctor does not rush to diagnose MS, since a variety of other diseases are included in the differential diagnosis. For instance, MS should be differentiated from other neuroinflammatory disorders.
MS is divided into the following groups, primarily based on clinical criteria, including clinical recurrence frequency, disease progression period and MRI lesion development:
Relapsing-remitting MS (RRMS): About 85% of cases
Progressive MS Secondary (SPMS)
Progressive Primary MS (PPMS)
MS (PRMS) progressive-relapsing
RRMS also contains the following two subgroups:
Clinically isolated syndrome (CIS): A single episode of neurological symptoms.
Benign MS: MS with almost total recovery between relapses and no physical impairment accumulation over time.
An inflammatory, demyelinating condition of the CNS leads to multiple sclerosis. The demyelinating lesions of MS, called plaques, occur as indurated areas in pathologic specimens, hence the name sclerosis.
Examination of the spinal cord and demyelinating brain lesions in patients with MS indicates myelin degradation, oligodendrocyte destruction, and reactive astrogliosis, often with relative sparing of the axon cylinder. The axon is also actively destroyed in some MS patients, however.
1. The location of lesions in the CNS typically determines the resulting form of clinical deficiency.
2. Some remyelination occurs when neural inflammation resolves in MS, but some regeneration of function that takes place in a patient may be due to plasticity of the nervous system.
3. Perivenular infiltration of lymphocytes and macrophages is also characterised by MS. Inflammatory cell infiltration occurs in the hippocampus, brainstem, spinal cord, and optic nerves.
4. The breakdown of the blood-brain barrier is one of the first steps in the development of lesions.
5. The increased expression of adhesion molecules on the surface of lymphocytes and macrophages appears to underlie the capacity of these inflammatory cells to cross the blood-brain barrier.
6. The elevated level of immunoglobulin G ( IgG) in the cerebrospinal fluid, which can be demonstrated on electrophoresis by an oligoclonal band pattern, indicates a significant humoral component to MS (i.e. B-cell activation).
7. In fact, MS lesions have shown variable degrees of antibody-producing plasma cell infiltration. An outline of demyelination is given in the image below.
The cause of MS is unclear, but several factors are likely to work in concert to induce the disease or sustain it. It has been hypothesised that when an environmental agent or occurrence (e.g., viral or bacterial infection, chemical exposure, lack of exposure to the sun) operates in combination with a genetic predisposition to immune dysfunction, MS results.
Genetic and biochemical aspects
Among monozygotic twins, the concordance rate for MS is only 20-35%, indicating that genetic factors have only a modest effect. The involvement, along with environmental effects, of predisposing non-Mendelian factors (i.e., epigenetic alteration in 1 twin) plays an important role. The risk of developing the condition is seven times higher for first-degree family members (children or siblings) of people afflicted with MS than in the general population, but the risk of family lifetime excess is just 2.5 to 5 percent.
Different variants of genes usually found in the general population, commonly referred to as polymorphisms, can result in different cellular expression gradations of those genes and, thus, of the proteins they encode. With MS susceptibility, an exaggerated response (e.g. elevated expression of a pro-inflammatory gene) to a given antigen may be produced by a polymorphism within the promoter region of a gene involved in immune reactivity, leading to uncontrolled proliferation of immune cells and autoimmunity.
Environmental factors: In early childhood, any environmental factor must affect. If a person remains in a low incidence MS area until he or she is 15, he or she will be at low risk even if he or she is moved to a high incidence area afterwards. On the other hand, despite living in higher occurrence regions, some ethnic groups (e.g., Eskimos) have no high MS frequency. Therefore, the exact position of geography vs genetics is uncertain.
Levels of Vitamin D:
Low levels of Vit D have been identified as one environmental factor leading to the growth of MS. By decreasing the development of pro-inflammatory cytokines and increasing the production of anti-inflammatory cytokines, vitamin D plays a role in regulating immune response; high circulating vitamin D levels also appear to be associated with a reduced risk of MS.
Signs and Symptoms
Multiple sclerosis, with remissions and recurring exacerbations, is characterised by varying CNS deficits. Exacerbations average around 1 every 2 years, although they differ significantly in frequency.
Although MS can progress and regress unpredictably, on the basis of that there are typical progression patterns:
Relapsing-remitting pattern: Exacerbations, when partial or full recovery occurs, or symptoms are stable, then they are alternate with remissions. Remissions can be months or years in length. Exacerbations can occur spontaneously, or an infection such as influenza may cause them.
Primary progressive pattern: With no remissions, the disease progresses steadily, while temporary plateaus can occur during which the disease does not progress. There are no apparent exacerbations, unlike in the relapsing-remitting pattern.
Secondary progressive pattern: It starts with recurrences alternating with remissions, accompanied by incremental disease progression (relapsing-remitting pattern).
Progressive relapsing pattern: The condition develops steadily, but rapid, clear relapses disrupt development. This pattern is infrequent.
The following are the most common initial symptoms of multiple sclerosis:
In one or more extremities, in the trunk, or on one side of the face, paresthesia.
A leg or hand weakness or clumsiness
Slight stiffness or irregular weakness of the limb, slight gait disruptions, vertigo, and mild affective disruptions are other typical early symptoms of MS; all typically display scattered CNS involvement and may be subtle.
Most MS patients have trouble regulating the bladder (e.g. frequency, urgency, hesitancy, incontinence, retention). Tiredness is widespread. Excess heat can temporarily intensify symptoms and signs.
Mild cognitive symptoms may be apathy, impaired judgement, or inattention. Affective disorders include emotional lability, euphoria, or depression. Depression can be reactive or partially due to MS cerebral lesions. There are seizures in a few patients.
Based on clinical results and supporting data from ancillary studies, MS is diagnosed. The following checks include:
Magnetic resonance imaging: the imaging tool of choice to validate MS and track the progression of the disease in the CNS
Evoked potential: Used for subclinical lesions to be identified; findings are not unique to MS
Lumbar puncture: can be helpful if MRI is not available or MRI results are not diagnostic; oligoclonal bands and intrathecal immunoglobulin G (IgG) development are evaluated for CSF.
Multiple sclerosis (MS) treatment has two aspects: immunomodulatory therapy (IMT) for the underlying immune deficiency and symptom-relieving or modifying treatments. IMT seeks to reduce the incidence of relapses and to delay development. Many disease-modifying agents have currently been approved for use only in relapsing types of MS. Mitoxantrone is also approved for the treatment of progressive and progressive relapsing MS secondary (long-term).
While therapy with immunomodulatory medications for the clinically isolated syndrome (CIS) (a single episode of neurological symptoms) has not yet become standard practise worldwide, research such as the TOPIC trial indicates that early intervention may be acceptable.
Acute Relapses Treatment:
Methylprednisolone (Solu-Medrol) from an acute exacerbation of MS can accelerate recovery. There is no conclusive evidence that it affects the course of the overall disease.
If steroids are contraindicated or ineffective, plasma exchange (plasmapheresis) may be used in the short term of severe attacks. Plasmapheresis is classified as “possibly successful” as a second-line treatment for recurrent MS exacerbations that do not respond to steroids in neurological diseases.
Relapsing-remitting MS Immunomodulatory Therapy:
Disease-modifying therapies have shown beneficial outcomes in patients with relapsing MS, including a reduced incidence and severity of clinical attacks. The development of disability and accumulation of lesions within the brain and spinal cord appears to be delayed by these agents. The disease-modifying agents for MS (DMAMS) currently approved for use by the US Food and Drug Administration (FDA) include the following:
Interferons (eg, beta-1a IFN, beta-1b IFN, beta-1a peginterferon)
Receptor modulators for sphingosine 1-phosphate (S1P) (e.g., siponimod, fingolimod, ozanimod)
Monoclonal (e.g., natalizumab, ocrelizumab, alemtuzumab) antibodies
Miscellaneous immunomodulators (e.g. monomethyl fumarate, glatiramer, mitoxantrone, teriflunomide, cladribine, dimethyl fumarate).