science

Pathology of multiple sclerosis

Pathology of multiple sclerosis is a science topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Pathology of multiple sclerosis rather than just read about it. In short: Multiple sclerosis (MS) can be pathologically defined as the presence of distributed glial scars (scleroses) in the central nervous system that must show dissemination in time (DIT) and in space (DIS) to be considered MS lesions. The scars that give the name to the condition are produced by the astrocyte cells attempting to heal old lesions.

Key takeaways

Pathology of multiple sclerosis belongs to science; place it in that map before memorising details.
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Connect Pathology of multiple sclerosis to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Pathology of multiple sclerosis from memory before moving on to harder problems.

Reference excerpt

Multiple sclerosis (MS) can be pathologically defined as the presence of distributed glial scars (scleroses) in the central nervous system that must show dissemination in time (DIT) and in space (DIS) to be considered MS lesions. The scars that give the name to the condition are produced by the astrocyte cells attempting to heal old lesions. These glial scars are the remnants of previous demyelinating inflammatory lesions (encephalomyelitis disseminata) which are produced by the one or more unknown underlying processes that are characteristic of MS. Apart from the disseminated lesions that define the condition, the CNS white matter normally shows other kinds of damage. At least five characteristics are present in CNS tissues of MS patients: Inflammation beyond classical white matter lesions (NAWM, normal-appearing white matter and NAGM, normal-appearing gray matter), intrathecal Ig production with oligoclonal bands, an environment fostering immune cell persistence, Follicle-like aggregates in the meninges (B-cells mostly infected with EBV) and a disruption of the blood–brain barrier even outside of active lesions. Confluent subpial cortical lesions are the most specific finding for MS, being exclusively present in MS patients. Though this feature can only be detected during an autopsy there are some subrogate markers under study Damage in MS consists also in areas with hidden damage (normal appearing white and gray matters) and two kinds of cortical lesions: Neuronal loss and cortical demyelinating lesions. The neural loss is the result of neural degeneration from lesions located in the white matter areas and the cortical demyelinating lesions are related to meningeal inflammation. The scars in the white matter are known to appear from confluence of smaller ones Currently the term "multiple sclerosis" is ambiguous and refers not only to the presence of the scars, but also to the unknown underlying condition that produces these scars. Besides clinical diagnosis uses also the term "multiple sclerosis" for speaking about the related clinical courses. Therefore, when referring to the presence of the scars is better to use the equivalent term astrocytic fibrillary gliosis.

Lesions consistent with MS

A combination of histologic and/or immunohistochemical stains can be used to visualize post-mortem MS characteristic lesions and to diagnose post-mortem "inflammatory demyelinating lesions consistent with MS":

hematoxylin and eosin stain (demonstrates tissue and cell morphology) myelin stains (Luxol fast blue/periodic acid-Schiff, Luxol fast blue/hematoxylin/eosin, or immunohistochemistry for myelin proteins) macrophage-specific markers (immunohistochemistry for KiM1P or CD68) stains for axons (Bielschowsky silver impregnation or immunohistochemistry for neurofilament protein) stains for astrocytes (hematoxylin and eosin or immunohistochemistry for glial fibrillary acidic protein) and stains for the different lymphocyte subtypes (immunohistochemistry for CD3, CD4, CD8, CD20, and/or CD138) These markers are specific for the different processes that drive the formation of plaques: inflammation, myelin breakdown, astrogliosis, oligodendrocyte injury, neurodegeneration, axonal loss and remyelination. MS lesions evolve differently during early versus chronic disease phases, and within each phase, different kind of activity appears. The classification system for the lesions was updated in 2017. This system classifies MS lesions as active, mixed active/inactive, or inactive lesions based on the presence and distribution of macrophages/microglia. They locate the slowly expanding lesions inside the mixed subtype and provide a description of the different lesion types and required staining techniques. To consider some lesions as a case of MS, even under autopsy, they must be disseminated in time and space. Dissemination in time can be shown by the stage of the lesion evolution. If only a lesion is present it could be a case of solitary sclerosis. MS is usually defined as the presence of disseminated lesions in space and time with no other explanation for them. Therefore, given the unspecificity of the lesions, several MS pathological underlying conditions have been found, which are now considered separate diseases. There are at least three kind of lesions that were historically considered inside the MS spectrum and now are considered as separate entities:

Anti-AQP4 disease Anti-MOG disease Anti-Neurofascin disease

Demyelination process

Lesions in MS are heterogeneous and there are four different patterns in which they start, probably due to different underlying pathogenesis. Nevertheless, it seems than the last stage of damage is similar for all of them. Traditionally it was thought that MS lesions were produced by CD4+ T-cells but after the discovery of anti-MOG and anti-NF demyelinating diseases, it has been noticed that most CD4+ cases are anti-MOG in reality, and now CD8+ cases are considered the real MS cases. In some cases (pattern II), a special subset of lymphocytes, called T helper cells or "CD4+ T-cells" play a key role in the development of the lesion in a way similar to the CD4+ attacks that appear in anti-MOG associated encephalomyelitis. In the standard cases, the trigger and the underlying condition of MS is a soluble factor produced by CD8+ T-cells (or maybe B-cells). Also B Cells have been implicated in the pathogenesis of MS, and some theoretical models link the presence of EBV-infected B-cells to the development of MS. The first stage of a MS lesion is thought to be the development of an area called "normal appearing white matter" (NAWM). In this area activated microglia appears, as shown by positron emission tomography. MS lesions appear in these areas as pre-active lesions without autoimmune infiltrates at this stage They show microglia activation and degeneration of the neuron axons without T-cell infiltration. Both problems appear together though it is not known which one is first. T-cells attack is followed by leaks in the blood–brain barrier where T-cells infiltrate causing the known demyelination.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Pathology of multiple sclerosis

Start with the simplest possible case. Write down what Pathology of multiple sclerosis claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In science, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Pathology of multiple sclerosis before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Pathology of multiple sclerosis ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Pathology of multiple sclerosis

In research: Pathology of multiple sclerosis appears in science research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Pathology of multiple sclerosis in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Pathology of multiple sclerosis is common in secondary-school and first-year university syllabi. It links to neighbouring topics Multiple sclerosis, Pathophysiology, so understanding it makes those chapters shorter.
In everyday life: Look for Pathology of multiple sclerosis outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Pathology of multiple sclerosis in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Pathology of multiple sclerosis means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Pathology of multiple sclerosis out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Pathology of multiple sclerosis in simple terms?

Why does Pathology of multiple sclerosis matter?

Because it connects several science ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Pathology of multiple sclerosis?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Pathology of multiple sclerosis.