P- Neurodegenerative Disorders Flashcards
__________ is the most debilitating neurologic disease among young adults and is due to autoimmune mechanism.
____________ occur primarily in children and are the result of inborn errors of metabolism.
MS is the most debilitating neurologic disease in young people.
Leukodystrophies occur in children as the result of inborn errors of metabolism of enzymes affecting the production and maintenance of myelin
What is selective vulnerability?
What 3 things determine the CNS components involved?
The brain is the most inhomogenous organ in the body. Even if the whole CNS is exposed to an insult, only specific regions, groups of cells or cell components will be damaged.
- location in nervous system
- shared biochemical properties [same neurotransmitter]
- undetermined factors
What CNS components are at highest risk for brain contusions? What is the basis?
The orbital and temporal regions are at highest risk for contusion because of the irregularities in the inner skull surface at these locations
What CNS components are at highest risk for ischemia? What is the basis?
- CA1 of hippocampus
- Purkinje cells of cerebellum
Because they have the highest concentration in glutamate receptors which can lead to excitotoxicity and cell death
[ischemia= low flow= build up of glutamate = excitotoxicity = apoptosis of neurons]
What CNS components are at highest risk for CO intoxication? What is the basis?
- globus pallidus
- substantia nigra
highest concentration of iron-containing substances and thus highest affinity for CO
What CNS component is at highest risk for methanol intoxication? Basis?
Putamen- unknown reasons
What CNS component is at highest risk for damage by chronic ethanol use?
anterior cerebellar vermis- unknown reason
What CNS component is at highest risk for damage by neurodegenerative disorders?
- Transmitter specific groups of neurons
2. glia
What 2 disorders disrupt myelin?
What is the basis of each?
- MS - autoimmune attack on myelin-associated antigens
2. Leukodystophies- deficiency in enzyme that produces or maintains myelin [inborn error of metabolism]
What is the major risk factor for developing AD?
Advancing age
1% of 60 year olds to 50% of 80year olds
How does AD manifest clinically?
What area of the brain is the deterioration of the brain localized to?
How long is the course of the disease?
What causes death in most AD patients?
It manifests as dementia:
- amnesia and atleast one of the following:
- apraxia, aphasia, agnosia, decreased exec func
There is generalized, global deterioration of the cerebral cortex [outer gray, neuron rich matter]
Onset is insidious, and the course of the disease can be a decade or more.
Death is usually caused by secondary illness that complicates the debilitated state [pneumonia, UTI, sepsis, trauma]
What are the 2 ways atrophy of the brain can manifest in patients with Alzheimer’s?
- cerebral cortical atrophy [narrowed, gyri, wide sulci]
2. hydrocephalus ex vacuo [dilated ventricles due to loss of brain parenchyma]
What are the chief neuropathologic features of AD?
- neurofibrillary tangles - in cytoplasm of neuron
2. senile plaques - in dendrites/axons
What is the pathophysiology behind a neurofibrillary tangle in Alzheimer’s?
Tau becomes hyperphosphorylated which:
- interferes with tau’s ability to bind microtubules leading to disruption of the neuronal cytoskeleton
- self-aggregation of tau into filaments
What are the 2 major components of senile plaques?
- dystrophic processes of neurons in a tangled array [neurites], many of which have phospho-tau
- extracellular deposits of B-amyloid [AB42]
What leads to the abnormal accumulation of B-amyloid in brain parenchyma or cerebral blood vessels [amyloid angiopathy]?
APP [amyloid precursor protein] gene is mutated leading to:
- pathologic cleavage of AB
- decreased clearance of B-amyloid
- combination
What 2 stains can be used in cerebral cortical sections to demonstrate amyloid angiopathy?
- Thioflavin-S will show up neon yellow
2. AB-IHC = antibody to parenchymal and leptomeningial vessels
What feature of Alzheimer’s is the best correlate to cognitive impairment?
The loss of synapses NOT the loss of bulk neurons from the brain.
Where are the following neurons located?
- cholinergic
- SSTergic
- noradrenergic
- serotoninergic
- dopaminergic
- basal forebrain nuclei
- intrinsic cortical nuclei
- locus ceruleus
- raphe in midbrain/pons
- substantia nigra [pc]
In what lobes of the brain are neurofibrillary tangles and senile plaques most abundant?
- medial temporal lobe
- hippocampus - neocortex
[areas of memory and cognition]