Multiple Sclerosis: Pathogenesis and Mechanisms
24 Questions
1 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to Lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

In multiple sclerosis, what is the primary mechanism by which activated macrophages contribute to demyelination?

  • Promoting the differentiation of B cells into antibody-secreting plasma cells targeting myelin.
  • Inhibiting the migration of autoreactive T lymphocytes across the blood-brain barrier.
  • Releasing injurious products that damage the myelin sheath. (correct)
  • Directly stimulating oligodendrocytes to produce defective myelin.

How does the disruption of the axonal cytoskeleton contribute to the pathology of demyelinating diseases?

  • By increasing the speed of nerve impulse conduction.
  • By promoting the regeneration of oligodendrocytes.
  • By directly triggering the autoimmune response against myelin.
  • By destabilizing the axon, leading to progressive axonal loss. (correct)

What is the primary role of CD4 Th1 cells in the pathogenesis of multiple sclerosis?

  • Secreting cytokines that activate macrophages and enhance demyelination. (correct)
  • Suppressing the activity of autoreactive B cells.
  • Directly attacking and killing oligodendrocytes.
  • Promoting the repair of damaged myelin sheaths.

Why are demyelinating diseases also referred to as myelinoclastic diseases?

<p>Because they involve the destruction or loss of myelin. (A)</p> Signup and view all the answers

Which of the following best describes the pattern of inheritance for susceptibility to multiple sclerosis?

<p>A multifactorial pattern involving genetic and environmental factors. (D)</p> Signup and view all the answers

How does myelin contribute to the metabolic efficiency of neurons?

<p>By decreasing the energy expenditure needed for maintaining ion gradients during nerve impulse propagation. (C)</p> Signup and view all the answers

What is the clinical significance of the relapsing and remitting pattern observed in many cases of multiple sclerosis?

<p>It reflects alternating periods of inflammation and partial recovery of neurologic function. (D)</p> Signup and view all the answers

In the context of multiple sclerosis, what is the role of the blood-brain barrier (BBB) in disease pathogenesis?

<p>The BBB, when compromised, allows inappropriate migration of autoreactive T lymphocytes, initiating inflammation. (D)</p> Signup and view all the answers

In lesions characterized by thinner than normal myelin sheaths with lighter staining, what is the primary mechanism contributing to this change?

<p>Partial and incomplete myelin loss or remyelination by surviving oligodendrocytes. (D)</p> Signup and view all the answers

Neuromyelitis optica (Devic’s disease) is characterized by which key clinical features?

<p>Relatively acute, concurrent development of visual symptoms (blindness) and spinal cord symptoms (paraplegia). (D)</p> Signup and view all the answers

Which of the following best describes the clinical course and pathological features of acute multiple sclerosis (Marburg type)?

<p>A rapidly progressing disease marked by subacute neurologic deterioration, widespread demyelination, and large, numerous plaques. (C)</p> Signup and view all the answers

Why is the treatment for multiple sclerosis considered 'unsatisfactory'?

<p>Current treatments only address the symptoms and offer limited benefit, often involving immunosuppressive agents with potential side effects. (B)</p> Signup and view all the answers

What is the typical etiology and timeframe for the development of acute disseminated encephalomyelitis (ADEM)?

<p>A monophasic demyelinating disease that typically follows a viral infection or viral immunization, with symptoms developing 1-2 weeks after the infection. (A)</p> Signup and view all the answers

What combination of clinical findings is most indicative of acute disseminated encephalomyelitis (ADEM) at its onset?

<p>Abrupt onset of headache, fever, confusion, and stiff neck. (C)</p> Signup and view all the answers

What pathological feature is most characteristic of acute disseminated encephalomyelitis (ADEM) in the brain?

<p>Symmetric involvement of the neuraxis with intense perivenous inflammation, lipid-laden macrophages, lymphocytes and perivenous demyelination. (B)</p> Signup and view all the answers

In the context of demyelinating diseases, what distinguishes the pattern of demyelination in ADEM from that typically observed in multiple sclerosis?

<p>ADEM presents with symmetrical involvement of the entire neuraxis and perivenous inflammation, while MS typically shows multifocal lesions. (C)</p> Signup and view all the answers

Which characteristic distinguishes active MS plaques from inactive plaques?

<p>Abundant macrophages containing lipid-rich, PAS-positive debris. (A)</p> Signup and view all the answers

What microscopic feature is characteristic of both active and inactive MS plaques?

<p>Relative preservation of axons despite myelin loss. (A)</p> Signup and view all the answers

What best differentiates shadow plaques from active or inactive plaques in multiple sclerosis?

<p>Incomplete myelin loss or evidence of remyelination. (D)</p> Signup and view all the answers

What explains the pink-tan appearance of recent MS plaques upon gross examination?

<p>Influx of macrophages and myelin breakdown products. (C)</p> Signup and view all the answers

Which region of the central nervous system is LEAST likely to show prominent plaque formation in multiple sclerosis?

<p>Cortical gray matter (D)</p> Signup and view all the answers

What pathological process primarily accounts for the sharply defined borders observed at the microscopic level in MS lesions?

<p>Localized inflammatory and demyelinating activity. (D)</p> Signup and view all the answers

What is the diagnostic significance of perivenular extension observed on MR images of MS plaques?

<p>Reflects the inflammatory process spreading from the perivascular spaces. (B)</p> Signup and view all the answers

An older MS plaque that appears grossly hyaline gray and rubbery likely indicates what?

<p>Advanced stage with astrocytic proliferation and gliosis. (B)</p> Signup and view all the answers

Flashcards

Demyelination

The loss of the myelin sheath around nerves, leading to slower signal conduction.

Multiple Sclerosis

An autoimmune demyelinating disorder with episodes of neurologic deficits.

Pathogenesis of Multiple Sclerosis

Immune response targeting myelin, often initiated by autoreactive T lymphocytes.

Immune Trigger

Inappropriate activation of the immune system against the myelin sheath.

Signup and view all the flashcards

CD4+ Th1 Cells

T cells that react to self myelin antigens and secrete cytokines in MS.

Signup and view all the flashcards

Environmental Risk Factors

Factors that may increase the likelihood of developing MS, such as geography and infections.

Signup and view all the flashcards

Relapsing-Remitting Course

The characteristic pattern of Multiple Sclerosis where symptoms flare up and then partially recover.

Signup and view all the flashcards

Oligodendrocytes

Cells responsible for producing the myelin sheath in the central nervous system.

Signup and view all the flashcards

Partial Myelin Loss

Thinner myelin sheaths due to incomplete demyelination or remyelination.

Signup and view all the flashcards

Neuromyelitis Optica

A condition with simultaneous visual and spinal cord symptoms, resembling MS but more destructive.

Signup and view all the flashcards

Acute Multiple Sclerosis

A rare, aggressive form of MS in young people leading to rapid neurologic decline.

Signup and view all the flashcards

ADEM

A monophasic demyelinating disease often following viral infections with sudden symptoms.

Signup and view all the flashcards

ADEM Symptoms

Includes headache, fever, confusion, and can escalate to severe neurological impairments.

Signup and view all the flashcards

Pathological Features of ADEM

Characterized by symmetric neuraxis involvement and intense perivenous inflammation.

Signup and view all the flashcards

Outcome of ADEM

Can be fatal, but many recover completely after the acute phase.

Signup and view all the flashcards

Treatment Options for MS

Immunosuppressive agents, including corticosteroids, show limited benefits.

Signup and view all the flashcards

Multiple Sclerosis Plaques

Irregular white matter plaques found in the CNS, especially in white matter, optic nerves, and spinal cord.

Signup and view all the flashcards

Recent Plaques Appearance

Recent plaques are pink-tan and soft in texture, indicating new damage.

Signup and view all the flashcards

Older Plaques Characteristics

Older plaques appear gray and are rubbery or cystic, indicating chronic damage.

Signup and view all the flashcards

Active Plaque

Characterized by ongoing myelin breakdown and inflammation with macrophages and lymphocytes present.

Signup and view all the flashcards

Inactive Plaque

Older lesions with decreased inflammation and myelin loss, showing astrocytic proliferation.

Signup and view all the flashcards

Shadow Plaques

Lesions with incomplete myelin loss; borders between normal and affected white matter are not sharply defined.

Signup and view all the flashcards

Demyelination Process

Complete destruction of myelin with relative preservation of axons and accumulation of macrophages.

Signup and view all the flashcards

Reactive Astrocytes

Astrocytes proliferate in response to injury, particularly in inactive plaques, indicating gliosis.

Signup and view all the flashcards

Study Notes

Pathology of Demyelinating Diseases

  • Demyelination is the loss of myelin, the protective sheath around nerve fibers
  • Myelin is produced by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS)
  • Myelin increases the speed and efficiency of nerve conduction.
  • Loss of myelin leads to decreased conduction velocity, axon instability and eventually, axonal loss.
  • Demyelinating diseases involve the myelin sheath and can affect the entire nervous system.

Types of Demyelinating Diseases

  • Multiple sclerosis (MS): An autoimmune demyelinating disorder characterized by distinct episodes of neurologic deficits (relapsing remitting).
    • It is the most common demyelinating disorder.
    • Females are more commonly affected.
    • Age of onset is typically any age, rare in children and elderly.
    • Clinical course is characterized by relapsing and remitting episodes of neurologic deficits, lasting weeks to months to years, with periods of partial recovery.
  • Acute disseminated encephalomyelitis (ADEM): A monophasic demyelinating disease following a viral infection or immunization.
    • Symptoms develop 1-2 weeks after infection.
    • Clinical features include abrupt onset of headache, fever, confusion, stiff neck, progressing to severe cases with convulsions, cerebellar ataxia, cranial nerve palsies or coma.
    • A significant percentage experience a fatal outcome.
    • Complete recovery is possible.
  • Acute necrotizing hemorrhagic encephalomyelitis: A fulminant and diffuse central nervous system demyelinating disease.
    • It's a severe, hyperacute form of acute disseminated encephalomyelitis, primarily affecting young and children.
    • Characterized by a rapid progression to coma and death within several days, and following an episode of an upper respiratory infection.
    • Grossly, the brain demonstrates grayish discoloration.
    • Microcopically, there is diffuse cerebral edema with petechial hemorrhages and large confluent areas of hemorrhagic necrosis.
    • Fibrinoid necrosis of venules with perivascular edema, fibrin deposition and neutrophilic infiltrations, culminating in perivascular demyelination.

Morphology of Demyelinating Diseases

  • MS:
    • Plaques are typically irregular, sharply circumscribed areas of demyelination found primarily in periventricular white matter, optic nerves and tracts, brainstem and spinal cord.
    • Plaques can also extend into grey matter.
    • Recent plaques appear pink-tan and soft, while older plaques show hyaline gray appearance, being more rubbery or cystic.
    • Variations in plaque size exist, from small foci to large confluent plaques.
  • ADEM:
    • Characterized by symmetrical involvement of the entire neuraxis.
    • Intense perivenous inflammation (hallmark) consisting of lipid-laden macrophages and lymphocytes, surrounding areas of perivenous demyelination, and relatively sparing of axons.
  • ANHE:
    • Characterized by widespread destruction of myelin, presence of large confluent areas of hemorrhagic necrosis and diffuse cerebral edema with petechial hemorrhages.
    • Fibrinoid necrosis of venules is evident, along with perivascular edema, fibrin deposition, and neutrophils infiltration.

Treatment of Demyelinating Diseases

  • Treatment for demyelinating diseases, such as MS, are largely unsatisfactory.
  • Immunosuppressive agents, including corticosteroids, can provide some benefit but aren't curative.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Quiz Team

Related Documents

Pathology of Demyelinating Diseases PDF

Description

Explore the pathogenesis of multiple sclerosis, focusing on the roles of macrophages, axonal cytoskeleton disruption. The lecture questions cover the roles of CD4 Th1 cells, myelin's function, and the clinical significance of relapsing-remitting patterns. The impact of the blood-brain barrier on disease progression is also discussed.

More Like This

Use Quizgecko on...
Browser
Open
Browser
Browser