6/18- Demyelinating Diseases (MS) Flashcards

1
Q

What cells make myelin in the central nervous system?

A

Oligodendroglia

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2
Q

What cells make myelin in the peripheral nervous system?

A

Schwann cells

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3
Q

___ cells may invest multiple axons, while ___ invest a single axon

A

Oligodendroglia cells may invest multiple axons, while Schwann cells invest a single axon

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4
Q

Classification of Myelin Disorders:

  • Central
  • Peripheral
  • Both
A

Central:

  • Multiple sclerosis
  • Post infectious encephalomyelitis

Peripheral:

  • Guillain-Barre Syndrome
  • Charcot-Marie-Tooth diseaes

Both:

  • Leukodystrophies
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5
Q

What clinical advancement has greatly helped in the diagnosis and understanding of demyelinating diseases?

A

(Especially MS)

Diffusion Tensor Imaging (DTI)

  • Revolutionizing our understanding of white matter tracts in health and disease
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6
Q

What may be seen in the gross neuropathology of MS?

A
  • Plaques may occur anywhere there is myelin (typically periventricular, subpial, junctional [white/grey])
  • Well-defined, clearly-demarcated gelatinous
  • Grey due to loss of lipid in myelin
  • May be symmetrical
  • Acute plaque may be pink
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7
Q

Characteristics of lesions/plaques in MS (time)?

A

Lesions are disseminated in space and time (multifocal); this is required for diagnosis

  • Onset typically in young adult life
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8
Q

What is this?

A

Periventricular demyelinating plaques in MS

Classic presentation of MS

  • Normal white matter
  • Grey area around ventricles (periventricular demyelinating plaques)
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9
Q

Stages of MS? Timeline?

A

Relapsing remitting phase

  • Attacks and recovery
  • All the drugs that treat MS work in this phase; this form can be favorably modified by immunomodulatory drugs

Secondary progressing phase

  • Relentless, steady decline in function
  • Typically occurs after a few years

Primary progressive MS

  • Relentlessly progressive from the onset
  • Not responsive to currently available immunomodulatory drugs
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10
Q

What is this?

A
  • White matter sunken and more white than normal
  • Large bilateral demyelinating plaques (MS)

If demyelination is occurring in frontal lobes, may get loss of executive function and other symptoms typically associated with dementia

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11
Q

What is this?

A

Demyelinating plaque in MS (dark spot in top right)

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12
Q

MRI is used for what in MS?

A
  • Detection of asymptomatic plaques
  • Aids in diagnosis
  • Disease activity can be followed throughout time
  • Aids in therapeutic trials and management
  • Can demonstrate dissemination in space and time
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13
Q

Describe the criteria (for MS) of dissemination in space? In time?

A

Dissemination in space (DIS)

  • Clinically asymptomatic lesions can be seen
  • Multiple widely distributed plaques can be identified

Dissemination in time (DIT)

  • Plaques show characteristics imaging feature depending on how old they are
  • Lesion of differing age indicate dissemination in time

McDonald Criteria codefies diagnosis using MRI

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14
Q

T/F: Plaques are present when the patient with MS is asymptomatic

A

True

  • Can have plaques that don’t result in many symptoms
  • Plaques can be used to assess relative activity, though, with fewer plaques being less active
  • … even at baseline, is active
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15
Q

What is this showing?

A

Left: Unstained pons

Right: Stained pons revealing MS

Normal myelin stains black or deep blue; plaques do not stain

  • Not knocking out a specific system
  • Not in a particular vascular territory
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16
Q

What is this?

A

Demyelination of the spinal cord: grey discoloration (right side) seen in MS

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17
Q

What is this?

A

Optic chiasm in MS

  • Demyelination in chiasm (-> bitemporal binocular heminopsia field defect)
  • Demyelination of optic n. (-> vision loss in one eye; optic neuritis)
18
Q

Epidemiology of MS?

A
  • Women > men
  • Onset typically in early adulthood
  • People who grew up far from the equator (e.g. Minneapolis native 3x greater risk than Houston)*

*Thought perhaps to be chronic VItamin D deficiency (role in bones, but also an immune regulator)

19
Q

What is this? Symptoms?

A

Demyelination in nerve root entry zone leading to paroxysmal symptoms (abnormal synthesis of signals)

  • Trigeminal neuralgia (severe episodic pain)
  • Hemifacial spasm
  • Radicular pain

For these symptoms in young, think MS; in mature, think vascular or mass

20
Q

What is Redlich-Obersteiner’s zone?

A

Transition between CNS and PNS myelin

21
Q

What is seen microscopically in MS?

A
  • Perivascular lymphocytic infiltrate
  • Loss of oligodendroglia
  • Myelin sheath stripping
  • Macrophage infiltration
  • Astrogliosis
  • Relative sparing of axons (especially in relapsing-remitting stage; immune system can shut down lymphocytes)
22
Q

What do therapeutics target in MS?

A

Cellular immunity (tamp it down!)

  • e.g. corticosteroids?
23
Q

What is this?

A

Perivascular lymphocytes in MS

  • Lymphocytic infiltrate around BV
24
Q

What is this?

A

Spinal cord demyelination showing:

  • Macrophages (cleaning up myelin debris or possibly stripping it off themselves)
  • Denuded axons (axons relatively spared)
25
Q

T/F: Oligodendroglia can divide to replace those lost in attacks of MS?

A

True

26
Q

What is this?

A

Macrophages in demyelinating disease (MS)

  • Cellular debris within
27
Q

Therapeutics in MS?

A
  • High dose corticosteroids for acute flares
  • Numerous immune system modulators (disease modulating therapy) are now available to slow or arrest progression

These include:

- Beta-interferon

- Copolymer I

(cost is a problem)

28
Q

What are some diseases of post-infectious demyelination?

Are these central or peripheral diseases?

A

These are central diseases

  • Acute disseminated encephalomyelitis (ADE) or (ADEM)
  • Acute hemorrhagic leukoencephalopathy (If you survive the attack, you will probably be okay)
29
Q

Neuropathological features of acute disseminated encephalomyelitis (ADE)?

A
  • Monophasic T-cell mediated hypersensitivity
  • Perivenular lymphocytes
  • Marked swelling
  • Scattered small foci or hemorrhage
30
Q

Neuropathological features of acute hemorrhagic leukoencephalopathy?

A
  • Hyperacute ADE
  • Swelling with multiple hemorrhages
  • Fibrinoid necrosis of vessels
31
Q

What is this?

A

Post-infectious leukoencephalopathy

  • Can see various areas of demyelination scattered around
  • Dissemination in space but not time (1 time event)
32
Q

What is this?

A

Post-infectious hemorrhagic leukoencephalopathy

  • Monophasic immune attack of CNS white matter
33
Q

What is a disease of post-infectious inflammatory peripheral demyelination?

A

Guillain-Barre Syndrome with inflammatory polyradiculoneuritis

34
Q

Characteristics (caused by, timeline, symptoms, treatment) of inflammatory polyradiculoneuritis in Guillain-Barre syndrome?

A
  • May follow infection or vaccination
  • Rapid progression
  • May lead to respiratory failure
  • Can be treated with plasma exchange (remove Abs from blood; immunosupressive)
  • Recovery typically takes weeks-months
  • Good outcome ultimately
  • Can relapse or become recurrent (rare)
35
Q

What are leukodystrophies?

Examples (3) with their deficiency and symptoms?

A

Genetic disorders of myelin (affect both central and peripheral myelin)

MLD- metachromatic leukodystrophy

  • Arylsulfatase
  • Metachromasia

Krabbe

  • Galactoceramidase
  • Globoid cells

ALD/AMLD

  • Transporter of Lignoceroyl-CoA ligase
  • Inflammation, demyelination, hypadernalism
36
Q

Characteristics of metachromatic leukodystrophy?

  • AR/AD/sex-linked?
  • Deficiency of what?
  • Result of deficiency?
  • Identified how?
  • Affects what population
  • Symptoms?
  • Diagnosis?
A

- Autosomal recessive

  • Peripheral and central nervous system involvement
  • Aryl sulfatase A deficiency (cerebroside sulfatase) with accumulation of galactosyl-3-sulfatide
  • Myelin destruction with sulfatide accumulation in ECM and in macrophages

- Identified by toluidine blue or acidified cresyl violet stain- product is brown [shift from cresyl violet staining normal myelin in orthochromatic fashion to cresyl violet staining myelin brown in a metachromatic fashion; color spectral shift]

  • Young children affected, also juvenile and adolescent forms
  • Intellectual disability, spasticity, blindness
  • Diagnosis: lack of aryl sulfatase A in urine or in culture fibroblasts
37
Q

Characteristics of Krabbe’s Leukodystrophy?

  • AR/AD/sex-linked?
  • Deficiency
  • Result of deficiency
A
  • Autosomal recessive
  • Galactocerbroside- beta-galactosidase deficiency
  • “Globoid cell” leukodystrophy due to accumulation of galactocerbroside in macrophages
  • Demyelination with multinucleated globoid cells
38
Q

What is this?

A

Multinuclear macrophage (globoid cell) seen in Krabbe’s disease

39
Q

Characteristics of Adrenoleukodystrophy?

  • AR/AD/sex-linked?
  • What regions affected?
  • Mechanism
  • Symptoms
  • Treatment
A
  • X-linked recessive inheritence
  • Parieto-occipital demyelination
  • Adult form involves spinal cord and peripheral nerves
  • Peroxisomal disorder: defect in peroxisomal membrane protein that imports acyl coenzyme A synthetase into peroxisome
  • Lorenzo’s oil- dietary supplement arrests progression
40
Q

What is this?

A

Parieto-occipital demyelination in adrenoleukodystrophy

41
Q

What is this?

A

Adrenoleukodystrophy

  • Posterior predominant
42
Q

What is this?

A

Frontal coronal section (left) and parietal coronal section (right) showing selective parieto-occipital demyelination in adrenoleukodystrophy