neurology: demyelinating illnesses in CNS Flashcards
what do demyelination diseases look like in the CNS?
damage to oligodendrocytes or their processes that myelinate axons –> usually autoimmune
what do demyelination diseases look like in the PNS?
damage to schwann cells from genetic deficits that impair the ability of schwann cells to produce myelin sheaths or autoimmune mechanisms
what is multiple sclerosis?
immune-mediated diseases directed against the CNS –> loss of myelin and eventual loss of axons
what are common findings of MS?
- chronic inflammatory findings
- white matter lesions throughout the brain and spinal cord
- pathological specimens are firm and indurated in areas of white matter loss
what is the most common demyelinating illness?
MS –> 3X more common in women, begins during adulthood
what is the etiology of MS?
- polygenetic etiology: involved genes are HLA2, IL2, IL7, IL17
- link to viral infections such as EBV (because of B-lymphocytes going into CNS due to virus)
- sun exposure and low levels of vitamin D
- other autoimmune diseases
what is the pathogenesis of MS?
2 phases:
1) active plaques: presence of typical leukocytes found in chronic inflammation (CD4, Th1, Th17, B-cells, macrophages and cytotoxic T-cells) –> destroys myelin and oligodendrocytes but more can still be produced
2) inactive plaques: loss of axons and eventually neurons with limited to no leukocytic infiltration and prominent gliosis
what are the characteristics of MS plaques?
Multiple well-circumscribed, irregularly shaped plaques that are firmer than the surrounding tissues
Commonly occur adjacent to the lateral ventricles, optic tracts, brainstem, cerebellum,
spinal cord
More prominent in areas rich in white matter
Over time, a degree of cerebral atrophy may be
noted
what are the active plaques in MS pathogenesis?
- leukocytes cross the BBB to the CNS
- helper T-cells initiate immune response against myelin
- helper T cells recruit other leukocytes (cytotoxic T-cells, macrophages) into white matter and activate them
- cytotoxic T-cells attack oligodendrocytes
- myelin basic protein specific B-lymphocytes are recruited into CNS to produce anti-MBP antibodies that destroy myelin sheath
what stains are used in MS?
Hematoxylin and eosin (H&E) stain shows perivascular infiltration of inflammatory cells
These infiltrates are composed of activated T
cells, B cells and macrophages
what is an MS flare?
flare= period of worsened neurological symptoms
what happens during an MS flare up?
build-up of helper T-cells and cytotoxic T-cells in the CNS that attack white matter components and B-cells that produce myelin-specific antibodies
In between flares, fewer chronic inflammatory cells detected
what are lymphocytic follicles?
areas where lymphocytes reside permanently –> prominent around the meninges and blood vessels
what is the pathogenesis of inactive plaques?
inactive plaques= plaques without prominent inflammation
axons degrade without myelin and oligodendrocytes –> destabilization of AP –> neural cell death
after demyelination, more sodium channels are redistributed along the axon, allowing AP conduction –> continuous conduction of AP requires more ATP –> neural metabolism consequences
what are common initial symptoms of MS?
Paresthesias in one or more extremities, the trunk, or one side of the face
Weakness or clumsiness of a leg or hand
Visual disturbances:
▪ Partial loss of vision and pain due to optic neuritis
▪ Diplopia
▪ Scotomas
▪ Nystagmus and dizziness
what are cognitive impairments of MS?
fatigue, depression, impaired cognition
what are sensory symptoms of MS?
paresthesia and loss of sensation, L’hermitte’s phenomenon (electrical shock sensation), pain
what are motor symptoms of MS?
bilateral, spastic weakness mostly in lower limbs, increased DTR, charcot triad (dysarthria, nystagmus, tremor), slurred speech
what are brainstem and spinal cord findings related to MS?
dizziness, bladder dysfunction, constipation, erectile dysfunction/genital anesthesia, urinary and fecal incontinence in advanced cases