Neuro: 17.6: Demyelinating Disorders Flashcards
What causes central pontine myelinolysis?
- rapid IV correction of hyponatremia
- *** “From low to high, your pons will die”
Which cell does the myelination in the PNS?
Schwann cells
What causes bowel/bladder/sexual dysfunction in MS?
involvement of the autonomic nervous system (ANS)
What does “panencephalitis” mean?
- pan = entire brain (both gray and white matter)
- encephalitis = inflammation of the brain
What is the outcome of subacute sclerosing panencephalitis (SSPE)?
progressive debilitating encephalitis –> death
Name 2 tests to diagnose multiple sclerosis (MS).
- MRI
- LP
This is a pair of tracts that allows crosstalk btw CN3 and CN6 nuclei; it coordinates horizontal eye mvmts.
the medial longitudinal fasciculus (MLF)
What are the clinical features of multiple sclerosis?
- blurred/nystagmus/loss of vision in 1 eye
- vertigo
- scanning speech
- internuclear ophthalmoplegia (INO)
- hemiparesis or unilateral loss of sensation
- lower extremity loss of sensation or weakness
- bowel/bladder/sexual dysfunction
What is glatiramer?
a treatment for MS
What is the prognosis for adrenoleukodystrophy?
- leads to long-term coma/death
- adrenal gland crisis
What is leukodystrophy?
- inherited mutations in enzymes necessary for the production or maintenance of myelin
- white matter dysfunction w/I the brain
What happens in metachromatic leukodystrophy?
myelin cannot be degraded –> myelin and sulfatides accumulate in lysosomes
This drug is a glycoprotein normally expressed by virus-infected cells –> antiviral, antitumoral properties.
interferon-beta
What are the SEs of interferon-beta?
- flu-like symptoms
- depression
- neutropenia
- myopathy
What happens in Type I hypersensitivity reactions?
- free antigen cross-links IgE on presensitized mast cells and basophils –> vasoactive amine release to postcapillary venules
- anaphylactic and atopic
- usually an immediate reaction
- *** “First and Fast”
In adrenoleukodystrophy, fatty acids cannot be degraded. Where do they then accumulate?
- adrenal glands
- white matter
- testes
What causes multiple sclerosis?
autoimmune destruction of CNS myelin AND oligodendrocytes
How does central pontine myelinolysis present?
acute paralysis- “locked-in syndrome”
Dx?
- viral inclusions within both the neurons (gray matter) and oligodendrocytes (white matter)
subacute sclerosing panencephalitis (SSPE)
How does metachromatic leukodystrophy present?
- ataxia
- dementia
What is another name for “locked-in syndrome?”
Osmotic demyelination syndrome
The CN3 (oculomotor) nucleus of the right eye is connected to the ______ of the left eye.
CN6 (abducens) nucleus
What causes Krabbe disease?
a deficiency of galactocerebroside beta-galactosidase –> destruction of myelin sheath
Are axons myelinated in the CNS or PNS?
both
Name 3 diseases in which the oligodendrocytes are injured.
- MS
- progressive multifocal leukoencephalopathy (PML)
- leukodystrophies
What causes blurred vision in MS?
involvement of the optic nerve
What causes scanning speech in MS?
involvement of the brainstem
What kind of hypersensitivity reaction is MS?
type IV = delayed, T-cell-mediated
“Locked-in syndrome” can occur with ____ or ____.
- central pontine myelinolysis
- a basilar artery stroke
Which is the most common leukodystrophy?
metachromatic leukodystrophy
What causes lower extremity loss of sensation or weakness in MS?
involvement of the spinal cord
When does subacute sclerosing panencephalitis (SSPE) present?
years after a measles infection (which usu. occurs in infancy)
What is another name for Charcot-Marie-Tooth disease?
hereditary motor and sensory neuropathy (HMSN)
What is another name for Osmotic demyelination syndrome?
“locked-in syndrome”
What MRI findings are diagnostic of multiple sclerosis (MS)?
- multiple white matter lesions separated in space and time
- periventricular plaques
Which nerve innervates the lateral rectus muscle?
CN 6- abducens
How does Charcot-Marie-Tooth disease present?
- foot deformities (pes cavus)
- lower extremity weakness
- sensory deficits
How is adrenoleukodystrophy transmitted?
X-linked
Each Schwann cell can myelinate _____ axons.
1
What is the Charcot triad of MS?
- Scanning speech
- Intention tremor/Incontenence/Internuclear ophthalmoplegia (INO)
- Nystagmus
- *** “Triad is a SIN”
What causes myelination disorders?
destruction of the myelin or oligodendrocytes
What causes hemiparesis or unilateral loss of sensation in MS?
involvement of the cerebral white matter
What causes Marcus Gunn pupils?
optic nerve damage or severe retinal injury–> an afferent pupillary defect
How is metachromatic leukodystrophy transmitted?
it’s an auto-recessive lysosomal storage disease
What is the most common chronic CNS disease of young adults?
multiple sclerosis
Which nerve innervates the medial rectus muscle?
CN3 - oculomotor
This is decreased bilateral pupillary constriction when light is shone in the affected eye (relative to the unaffected eye).
Marcus Gunn pupils
How is Krabbe disease transmitted?
auto. recessive
HLA-DR2 is associated with which diseases?
- MS
- hay fever
- SLE
- Goodpasture
What gross findings can be seen on a brain specimen from an MS pt?
patches of gray within the white matter (areas of demyelination)
The CN3 (oculomotor) nucleus of the right eye is connected to the CN6 (abducens) nucleus of the left eye with the _____ in between.
medial longitudinal fasciculus (MLF)
What are Schwann cells derived from?
neural crest cells
Dx?
- a JC virus infection of oligodendrocytes that is reactivated due to immune suppression –> demyelination of the CNS
progressive multifocal leukoencephalopathy
What is the tx for MS, both acutely and long-term?
- acute = high-dose steroids
- long-term = interferon-beta, natalizumab, glatiramer
Dx?
- blurred/nystagmus/loss of vision in 1 eye
- vertigo
- scanning speech
- internuclear ophthalmoplegia (INO)
- hemiparesis or unilateral loss of sensation
- lower extremity loss of sensation or weakness
- bowel/bladder/sexual dysfunction
multiple sclerosis
Name the hypersensitivity reaction:
- cytotoxic/antibody mediated
- IgM, IgG bind to fixed antigen on cell –> destruction via MAC
Type II hypersensitivity reaction
Who typically gets adrenoleukodystrophy? Why?
- usually males
- it’s X-linked
What is Charcot-Marie-Tooth disease?
an auto dominant, progressive nerve disorder related to the defective production of proteins involved in the structure and function of peripheral nerves or the myelin sheath
How does progressive multifocal leukoencephalopathy present?
rapidly progressing neuro. signs –> death
What causes Charcot-Marie-Tooth disease?
- auto dominant inheritance
- defective production of proteins involved in the structure and function of peripheral nerves or the myelin sheath
What accumulates in adrenoleukodystrophy?
long-chain fatty acids
What causes progressive multifocal leukoencephalopathy?
a JC virus infection of oligodendrocytes that is reactivated due to immune suppression –> demyelination of the CNS
Marcus Gunn pupils are associated with _____.
MS
In myelination disorders, what damage occurs to the axon?
myelin is damaged but the axons themselves are preserved
What accumulates in Krabbe disease?
- galactocerebroside
- psychosine
What causes adrenoleukodystrophy?
impaired addition of coenzyme A to long-chain fatty acids
Each oligodendrocyte can myelinate _____ axons.
up to 30
What does CN3 (oculomotor) innervate?
the medial rectus muscle of the eye
What happens in Type IV hypersensitivity reactions?
- sensitized T cells encounter antigen –> release cytokines –> activate macs
- *** delayed reaction
In metachromatic leukodystrophy, myelin and sulfatides cannot be degraded. Where do they then accumulate?
in lysosomes
Dx?
- an auto dominant, progressive nerve disorder related to the defective production of proteins involved in the structure and function of peripheral nerves or the myelin sheath
Charcot-Marie-Tooth disease
Name 2 drugs that increase the risk of progressive multifocal leukoencephalopathy.
- natalizumab
- rituximab
What is natalizumab?
- a tx for MS and Crohns
- an antibody to alpha-4-integrin
What are Marcus Gunn pupils?
when there is decreased bilateral pupillary constriction when light is shone in the affected eye (relative to the unaffected eye)
Give an example of the findings in internuclear ophthalmoplegia (INO). What causes this?
- Ex: as the pt to look to the Left: left eye looks left right eye doesn’t move left
- cause: damage to the medial longitudinal fasciculus (MLF) connecting CN6 of L eye to CN3 of R eye
What will happen if the cerebral white matter is involved in an MS pt?
- hemiparesis
- unilateral loss of sensation
How does Krabbe disease present?
- peripheral neuropathy
- developmental delay
- optic atrophy
- globoid cells
What causes internuclear ophthalmoplegia (INO) in MS?
involvement of the medial longitudinal fasciculus (MLF)
What is another name for hereditary motor and sensory neuropathy (HMSN)?
Charcot-Marie-Tooth disease
How does interferon-beta work?
it is a glycoprotein normally expressed by virus-infected cells –> antiviral, antitumoral properties
Based on these LP findings, what is the diagnosis?
- increased lymphocytes
- increased Ig with oligoclonal IgG bands
- myelin basic protein
multiple sclerosis (MS)
What is the prognosis for progressive multifocal leukoencephalopathy?
death
What is the medial longitudinal fasciculus (MLF)?
- a pair of tracts that allows crosstalk btw CN3 and CN6 nuclei
- coordinates horizontal eye mvmts
What will happen if the medial longitudinal fasciculus (MLF) is involved in an MS pt?
internuclear ophthalmoplegia (INO)
How does natalizumab work?
it’s an antibody to alpha-4-integrin
This is a tx for MS and Crohns; an antibody to alpha-4-integrin.
natalizumab
What happens in Type III hypersensitivity reactions?
- immune-complex mediated
- antigen-antibody (IgG) complexes activate complement –> attracts neutrophils –> release lysosomal enzymes
- *** “Type 3 is 3 things stuck together: antigen-antibody-complement”
What causes metachromatic leukodystrophy?
it’s an auto recessive deficiency of arylsulfatase (this is a lysosomal storage disease)
What is an oligodendrocyte?
a cell in the CNS that does the myelination
What happens in Type II hypersensitivity reactions?
- cytotoxic/antibody mediated
- IgM, IgG bind to fixed antigen on cell –> destruction via MAC
- *** “Type 2 is cy-2-toxic”
What LP findings are diagnostic of multiple sclerosis (MS)?
- increased lymphocytes
- increased Ig with oligoclonal IgG bands
- myelin basic protein
What genetic marker is assoc. with multiple sclerosis?
HLA-DR2
What does a deficiency of arylsulfatase cause?
metachromatic leukodystrophy
An optic nerve damage or severe retinal injury–> an afferent pupillary defect called ______.
Marcus Gunn pupils
Dx?
- focal demyelination of the pons due to rapid IV correction of hyponatremia
central pontine myelinolysis
What does CN6 (abducens) innervate?
the lateral rectus muscle of the eye
What happens in Krabbe disease?
galactocerebroside cannot be degraded –> accumulates in macrophages
What happens when hypernatremia is corrected too quickly?
- cerebral edema/herniation
- *** “From high to low, your brain will blow”
In general, these are inherited mutations in enzymes necessary for the production or maintenance of myelin (white matter dysfunction w/I the brain).
leukodystrophies
What will happen if the autonomic nervous system (ANS) is involved in an MS pt?
bowel/bladder/sexual dysfunction
Dx?
- a deficiency of galactocerebroside-beta-galactosidase –> destruction of myelin sheath
Krabbe disease
Dx?
- paralysis of ALL voluntary movements EXCEPT for the eyes
“locked-in syndrome”
What causes vertigo in MS?
involvement of the brainstem
What will happen if the brainstem is involved in an MS pt?
- vertigo
- scanning speech
What will happen if the optic nerve is involved in an MS pt?
blurred/loss of vision in 1 eye
Dx?
- autoimmune destruction of CNS myelin and oligodendrocytes
multiple sclerosis
What accumulates in metachromatic leukodystrophy?
- myelin
- sulfatides
What destroys Schwann cells?
Guillan-Barre syndrome (campylobacter)
Dx?
- impaired addition of coenzyme A to long-chain fatty acids
adrenoleukodystrophy
Rapid IV correction of ______ can cause central pontine myelinolysis.
- hyponatremia
- *** “From low to high, your pons will die”
What is “locked-in syndrome?”
paralysis of ALL voluntary movements EXCEPT for the eyes
What is scanning speech similar to?
drunk speech
What will happen if the spinal cord is involved in an MS pt?
lower extremity loss of sensation or weakness
Who gets central pontine myelinolysis?
severely malnourished pts (alcoholics, liver disease, etc)
Name the hypersensitivity reaction:
- sensitized T cells encounter antigen –> release cytokines –> activate macs
- *** delayed reaction
Type IV hypersensitivity reaction
What color is the white matter within the brain? Why?
- white
- it’s heavily myelinated
What causes subacute sclerosing panencephalitis?
persistent brain infection by measles virus
Name the hypersensitivity reaction:
- free antigen cross-links IgE on presensitized mast cells and basophils –> vasoactive amine release to postcapillary venules
- anaphylactic and atopic
- usually an immediate reaction
Type I hypersensitivity reaction
What characterize subacute sclerosing panencephalitis (SSPE)?
viral inclusions within both the neurons (gray matter) and oligodendrocytes (white matter)
Where does multiple sclerosis most commonly occur in the world?
regions far from the equator
Name the hypersensitivity reaction:
- immune-complex mediated
- antigen-antibody (IgG) complexes activate complement –> attracts neutrophils –> release lysosomal enzymes
Type III hypersensitivity reaction
Which cell does the myelination in the CNS?
oligodendrocytes
What is central pontine myelinolysis?
focal demyelination of the pons
Why is myelin basic protein found in the CSF in MS?
bc myelin is being degraded
What color is the gray matter in the brain? Why? Where is it located?
- gray
- no myelin
- at the periphery
In Krabbe disease, galactocerebroside cannot be degraded. Where does it then accumulate?
in macrophages
What does a persistent brain infection by measles virus cause?
subacute sclerosing panencephalitis (SSPE)
