6/18- Demyelinating Diseases (MS) Flashcards Preview

Term 5: Neuro > 6/18- Demyelinating Diseases (MS) > Flashcards

Flashcards in 6/18- Demyelinating Diseases (MS) Deck (42):

What cells make myelin in the central nervous system?



What cells make myelin in the peripheral nervous system?

Schwann cells


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

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


Classification of Myelin Disorders:

- Central

- Peripheral

- Both


- Multiple sclerosis

- Post infectious encephalomyelitis


- Guillain-Barre Syndrome

- Charcot-Marie-Tooth diseaes


- Leukodystrophies 


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

(Especially MS)

Diffusion Tensor Imaging (DTI)

- Revolutionizing our understanding of white matter tracts in health and disease 

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What may be seen in the gross neuropathology of MS?

- 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


Characteristics of lesions/plaques in MS (time)?

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

- Onset typically in young adult life


What is this?

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Periventricular demyelinating plaques in MS

Classic presentation of MS

- Normal white matter

- Grey area around ventricles (periventricular demyelinating plaques)


Stages of MS? Timeline?

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


What is this? 

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- 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


What is this?

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Demyelinating plaque in MS (dark spot in top right)


MRI is used for what in MS?

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

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


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


- 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


What is this showing?

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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


What is this?

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


What is this? 

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Optic chiasm in MS

- Demyelination in chiasm (-> bitemporal binocular heminopsia field defect)

- Demyelination of optic n. (-> vision loss in one eye; optic neuritis)


Epidemiology of MS?

- 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)


What is this? Symptoms? 

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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


What is Redlich-Obersteiner's zone?

Transition between CNS and PNS myelin


What is seen microscopically in MS?

- 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)


What do therapeutics target in MS?

Cellular immunity (tamp it down!)

- e.g. corticosteroids?


What is this?

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Perivascular lymphocytes in MS

- Lymphocytic infiltrate around BV


What is this?

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Spinal cord demyelination showing:

- Macrophages (cleaning up myelin debris or possibly stripping it off themselves)

- Denuded axons (axons relatively spared)


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



What is this? 

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Macrophages in demyelinating disease (MS)

- Cellular debris within


Therapeutics in MS?

- 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)


What are some diseases of post-infectious demyelination?

Are these central or peripheral diseases?

These are central diseases

- Acute disseminated encephalomyelitis (ADE) or (ADEM)

- Acute hemorrhagic leukoencephalopathy (If you survive the attack, you will probably be okay)


Neuropathological features of acute disseminated encephalomyelitis (ADE)?

- Monophasic T-cell mediated hypersensitivity

- Perivenular lymphocytes

- Marked swelling

- Scattered small foci or hemorrhage


Neuropathological features of acute hemorrhagic leukoencephalopathy?

- Hyperacute ADE

- Swelling with multiple hemorrhages

- Fibrinoid necrosis of vessels


What is this?

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Post-infectious leukoencephalopathy

- Can see various areas of demyelination scattered around

- Dissemination in space but not time (1 time event)


What is this?

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Post-infectious hemorrhagic leukoencephalopathy

- Monophasic immune attack of CNS white matter


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

Guillain-Barre Syndrome with inflammatory polyradiculoneuritis


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

- 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)


What are leukodystrophies?

Examples (3) with their deficiency and symptoms?

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

MLD- metachromatic leukodystrophy

- Arylsulfatase

- Metachromasia


- Galactoceramidase

- Globoid cells


- Transporter of Lignoceroyl-CoA ligase

- Inflammation, demyelination, hypadernalism


Characteristics of metachromatic leukodystrophy?

- AR/AD/sex-linked?

- Deficiency of what?

- Result of deficiency?

- Identified how?

- Affects what population

- Symptoms?

- Diagnosis?

- 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

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Characteristics of Krabbe's Leukodystrophy?

- AR/AD/sex-linked?

- Deficiency

- Result of deficiency

- Autosomal recessive

- Galactocerbroside- beta-galactosidase deficiency

- "Globoid cell" leukodystrophy due to accumulation of galactocerbroside in macrophages

- Demyelination with multinucleated globoid cells


What is this? 

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


Characteristics of Adrenoleukodystrophy?

- AR/AD/sex-linked?

- What regions affected?

- Mechanism

- Symptoms

- Treatment

- 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


What is this? 

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Parieto-occipital demyelination in adrenoleukodystrophy


What is this?

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- Posterior predominant


What is this? 

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