Intro to Demyelinating Disorders Flashcards
What cells are shown below?
insert diagram
What are glial cells?
neural tissue cells that do not propagate an action potential but support and protect neurons
When does myelination begin?
- third trimester
- increases rapidly at birth
- continues throughout life
- oligodendrocyte = neuroepithelial
origin from neural tube - schwann cell = neural crest origin
Myelin is
a membranous cytoplasmic projection (lamellipodum) of an oligodendrocyte or a schwann cell that surrounds a neuronal axon forming the protective sheath
Schwann cell
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Myelination in the CNS vs PNS
- CNS: one oligodendrocyte can
myelinate up to 50 axons - PNS: one schwann cell myelinates one
axon - PNS: myelin sheaths are thicker in
diameter - CNS: axon >0.2 micrometers to be
myelinated - PNS: 1-2 micrometers to be myelinated
Oligodendrocyte and Schwann cell origin
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Which fibers are myelinated earlier in development? Sensory or Motor fibers?
Sensory fibers
Myelination in the CNS can be intrinsic or adaptive.
- intrinsic = early on during birth and
early childhood - adaptive = as neuronal network forms
- dwindles with age
What promotes the proliferation of oligodendrocytes?
Astrocytes
In the PNS how is myelination initiated?
proteins expressed on axon surface interact with glial cell receptors and promote the differentiation of progenitor cells to mature myelinating schwann cells
What is the main component of the myelin sheath?
primarily plasma membrane so
Lipid
like cholesterol
How is adaptive myelination initiated?
proteins expressed on axon surface interact with receptors on glial cells and promote the differentiation of progenitor cells to mature myelinating cells
Myelin Sheath
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The juxtaparanodal area of the axon is rich in
K+ voltage gated ion channels
What is the bare area of the axon called?
Node/nodal area
Schmidt-Lanterman incisures are found
between the internodal lamellae formed by schwann cells in the pns
Nodes of Ranvier:
- are
- contain
- gap between two adjacenet myelin
sheaths across an axon is called the
node of Ranvier - nodes of ranvier contain clusters of
voltage gated sodium channels - electrical current generated ollowing
depolarisation travels across the
insulated internode segment, with little
change to the next node causing
depolarisation
Label the diagram below
insert node of ranvier diagram
Saltatory Conduction:
- is
- advantages
- action potentials leap from node to node,
increasing conduction velocity - reduces loss of electrical current across axon
- unmyelinated = 0.5-2m/s, myelinated = 70-
100 m/s - increased efficiency of electrical
transmission as less ion channels are
needed (only ones at nodes) -> saves energy
for cell
Saltatory Conduction:
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Demyelinating Diseases:
damage to the myelin sheath
Dysmyelinating Disease:
abnormal formation of the myelin sheath
Demyelinating Diseases: Pathological Effects:
- reduced conduction velocity
- reduced distance in propagation of signal
across an axon - both efferent and afferent neurons can be
affected as well as higher functions, such as
cognition
Pathology of Demyelinating Diseases: Causes:
- brain injury or ischaemia
- toxins/chemicals
- metabolic
- neurodegenerative
- infection
- autoimmune effects (myelin sheath proteins
are antigenic)
Demyelinating Diseases: Symptoms:
- visual impairment
- cognitive changes
- speech impairment
- balance problems
- incoordination
- sensory loss
- weakness
- incontinence
- pain
- fatigue
Multiple Sclerosis:
- is
- incidence
- causes
- autoimmune demyelinating disease
- most common demyelinating disease with 1
in 1000 incidence - increased incidence in females
- genetic susceptibility and environmental
triggers
Multiple Sclerosis: Subtypes (3):
- relapsing-remitting = episodes of relapse
followed by remission, in the majority of
cases without complete repair - primary progressive = no periods of
improvement or relapse - secondary progressive = with relapse-
remission phase followed by progressive
disease years later with no remission phase
Multiple Sclerosis:
What leads to ongoing symptoms, accumulation of neurologic deficits and disability?
failure of remyelination
Multiple Sclerosis: Clinical Features:
- earliest presentation generally visual
impairment due to optic nerve affected - not all cases of optic neuritis develop MS
- ataxia
- nystagmus
- sensory and motor impairment of trunk and
limbs - loss of bladder control
Multiple Sclerosis: Treatment:
- steroids
- disease modifying treatments
- aim to control immune response to
decrease the rate and severity of replace
episodes - social prescribers
Multiple Sclerosis: Pathophysiology:
- T helper and B cells involved
- secrete cytokines that recruit macrophages
and other leucocytes that destroy myelin - leading to the formation of white matter
lesions called plaques - plaques can be active; containing
macrophages, broken down myelin and
lymphocytes - inactive plaques = resolved inflammation,
astrocyte proliferation and no myelin-gliosis
that can lead to the formation of a glial scar
Multiple Sclerosis:
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As age increases, remyelination is
less efficient
Autoimmune Demyelinating Diseases:
- demyelination due to immune function can
follow viral infections, even mild ones - caused by cross reactivity between myelin
proteins and immune cells/antibodies - the resulting diseases are acute and
monophasic
Acute Disseminated Encephalomyelitis (ADEM):
- autoimmune demyelinating disease
following viral infection - non-localised symptoms (headache,
lethargy, coma) - rapid progression with either complete
recovery or fatality in a minority of cases
Neuromyelitis optica:
optic nerve and spinal cord affected by autoimmune demyelination
Gullian-Barre Syndrome:
- autoimmune demyelinating disease of the
PNS
Guillain-Barre Syndrome: Presentation:
- often following infection like diarrhoeal
illness (campylobacter), upper respiratory
tract infection, COVID, hep E - progressive weakness over 2-4 weeks,
reaches nadir by 4-6 weeks - affects arms/legs/facial
muscles/speech/swallowing/breathing - may affect autonomic nervous system
- varying degrees of severity
- recovery thereafter (may not be complete)
Gullian-Barre Syndrome is a monophasic illness.
True or False?
True
Guillain-Barre Syndrome: Treatment:
- plasma exchange
- IV immunoglobulins
Guillain-Barre Syndrome: Subtypes:
- acute demyelinating polyradiculoneuropathy
(AIDP): europe, north ameria - acute motor axonal neuropathy (AMAN):
asia
Dysmyelinating Diseases: Leukodystrophies:
- are, cause, nature
- inherited diseases that emerge at a young
age and are progressive
Krabbe Disease:
- dysmyelinating leukodystrophy
- autosomal recessive
- causes by build up of cytotoxic metabolic
compound which inhibits myelin sheath
formation - appears between 3-6 months of age, survival
beyond 2 years is rare - loss of myelination in both CNS and PNS;
loss of oligodendrocytes
Metachromatic Leukodystrophy:
- dysmyelinating leukodystrophy
- autosomal recessive
- affects macrophages
Adrenoleukodystrophy:
- dysmyelinating leukodystrophy
- x linked recessive
- young males affects
- 10 years of life max
Charcot-Marie-Tooth Disease:
- hereditary heterogenous (dominant) disease
- dysmyelinating leukodystrophy in some
subtypes - mutations in different proteins linked
- progressive disease that usually presents
between 0-20 years of age - CMT1 are subtypes caused by demyelination
when the mutation is autosomal dominant - CMT4 when autosomal recessive which is the
most rare and severe - CMT2 subtypes affect neuronal axons
Remyelination: CNS:
- regenerative process
- axon regeneration is limited in CNS but
remyelination occurs - remyelination relies on oligodendrocytes
and the differentiation of oligodendrocyte
precursor cells (OPCs) - success of remyelination depends on the
location of a lesion, presence of OPCs,
degree of inflammation and the presence of
gliosis
Remyelination does occur in MS patients however is negatively affected by
disease progression
Remyelination: PNS:
- schwann cells can proliferate and
remyelinate axons - depends on the presence of progenitor cells
and successful differentiation - in comparison with CNS, schwann cells
create a positive growth environment that
promotes both axon growth and
remyelination in the event of injury
