Pathology - Neurodegenerative Diseases and Demyelinating Diseases Flashcards
Which neurodegenerative disorder is caused by a virus in immunocompromised patients? Which virus is it? Which cell types in the CNS are destroyed?
Progressive multifocal leukoencephalopathy is caused by JC virus, a type of polyomavirus. Oligodendrocytes are killed.
A patient who appears that they are likely homeless presents with decreased level of consciousness and a history of nausea and vomiting, and you find that their serum Na+ is 125mEq/L.
You give them hypertonic saline. Next time you check on the patient, they seem dead except for an intact pupillary light reflex and they can blink. WTF did u do wrong? What is the Dx?
Correcting hyponatremia too quickly can cause central pontine myelinolysis –> locked in syndrome.
See photo - note the lack of blue (myelin) in the pons.
In what general geographic region is the prevalence of MS highest?
Northern latitudes
At what age does MS most often present?
Between 20 and 30 years old
What criteria is used to make the diagnosis of MS clinically?
Two lesions separated by time and space
What CSF findings are indicative of a diagnosis of MS?
Oligoclonal bands (of IgG)
Specifically where in the brain do MS lesions tend to occur? How can you tell the difference between new and old lesions?
The lesions occur in periventricular areas.
New ones will ring-enhance w/ gadolinium, while old ones appear as areas of demyelination.
Identify the type of brain matter indicated by the arrows. What is your Dx based on this histo slide?
Bottom left is white matter, bottom right is gray matter. The big white patch is an area of demyelination from MS.
What’s up wit it?
MS lesion
What is tumefactive multiple sclerosis?
When someone has MS with a fucking huge lesion that has mass effect, edema, or ring enhancement.
What is your differential diagnosis for this?
MS or progressive multifocal leukoencephalopathy (its PML but Rendi said you’ll never have to differentiate the two via histology)
Regarding metachromatic leukodystrophy…
What is the inheritance pattern?
What is the specific enzymatic defect and product that gets built-up?
What is the over-arching effect that this has on the CNS?
What symptoms does it cause?
Autosomal recessive
Defective arylsulfatase A –> cerebroside sulfate build-up
Cerebroside build-up causes demyelination of neurons in the CNS
Presents as dementia, can progress to motor problems
Which virus is thought to trigger the development of MS via molecular mimicry?
EBV
Regarding Krabbe’s disease…
What is the inheritance pattern?
What is the specific enzymatic defect and product that gets built-up?
What is the over-arching effect that this has on the CNS?
What symptoms does it cause?
Autosomal recessive
Galactocerebroside beta mutation -> build up of glucocerebroside and psychosine -> demyelination of peripheral and CNS nerves
Symptoms: peripheral neuropathy, developmental delay, irritability and violent crying in infants, optic nerve atrophy
Regarding adrenoleukodystrophy…
What is the inheritance pattern?
What is the specific cellular defect and product that gets built-up?
What is the over-arching effect that this has on the CNS?
What symptoms does it cause?
X-linked recessive
Disrupted very long chain fatty acid metabolism -> build-up of VLFAs in CNS, testes, adrenal gland -> CNS atrophy and adrenal atrophy
Symptoms: behavior, visual, auditory deficits and adrenal insufficiency -> death
What are the inheritable mutations that can cause early-onset Alzheimer’s?
What genes confer greater risk for developing sporadic Alzheimer’s?
Early onset: Presinilin 1 and 2 genes
Sporadic: e4 allele of apolipoprotein-E = greater risk (e2 is protective!)
Why do people w/ Down syndrome have a greater risk for developing Alzheimer’s?
The gene for the APP protein is on chromosome 21
What is the most noticeable gross pathologic finding of a brain from a patient with advanced Alzheimer’s?
Cortical atrophy, most extensively in the frontal, temporal, and parietal lobes
WTF is this, what is it made out of, and what disease is it seen in?
Amyloid plaque, made ouf ot A-beta amyloid, seen in Alzheimer’s
This is from a brain. What is your Dx? What sequelae are associated with this?
That is amyloid (apple-green birefringence under polarized light).
Amyloid deposition in vessels weakens them -> risk for cerebral hemorrhage
Name three major histopathological features of Alzheimer’s disease and what each is made out of.
Amyloid plaques made from A-beta amyloid
Neurofibrillary Tangles made out of Tau protein
Neuronal loss
This is from a brain. What it is? What is it made of?
Neurofibrillary tangle (tau protein)
What type of dementia is characterized by severe atrophy of the frontal and temporal cortex leading to behavoiral and language problems, but sparing the memory? What is a histopathologic feature of this disease?
Frontotemporal dementia (aka Pick’s disease)
Round aggregates of tau protein are seen in cortical neurons
What is your Dx?
Frontotemporal dementia (Pick’s)
How quickly do prion-mediated encephalopathies progress?
Really fucking quickly
What histopathologic feature is found in Creutzfeldt-Jakob Disease (CJD)? What is the form of prion that is infectious?
Spongiform change in the cerebral cortex. PrPsc form is the bad one
What are the five major clincal features of Parkinson’s disease?
TRAPS:
Tremor (pill-rolling tremor at rest)
Rigidity (cogwheel)
Akinesia/bradykinesia
Postural instability
Shuffling gait
What is the structural cause of Parkinson’s disease?
Loss of dopaminergic neurons in the substantia nigra.
What is a histopathologic feature of Parkinson’s disease? What are these made out of?
Lewy bodies in the midbrain - made of alpha-synuclein
What it is? What disease(s) is this seen in?
Lewy bodies seen in Parkinson’s or Lewy Body Dementia
What differentiates Lewy Body Dementia from Parkinson’s both clinically and histopathologically?
Lewy body dementia manifests as dementia! With Parkinson’s, dementia is a vary late manifestation. This is because Lewy bodies in Lewy body dementia accumulate in the cortex.
Regarding Huntington’s disease…
Describe the inheritance pattern and important details regarding genetics (chromosome, nucleotides, paternal/maternal inheritance differences).
Describe the clinical features.
Autosomal dominant, CAG repeats on chromosome 4 (>40 repeats), with anticipation occurring if inherited from dad (expansion of the repeats occurs during spermatogenesis).
Clinical features: age of onset 30s-40s, chorea (writhing movements due to loss of GABA from the caudate nucelus), dementia, depression
What portions of the spinal cord are most often damaged in ALS? What enzymatic defect is associated with ALS?
Lateral corticospinal tract and anterior horn. Superoxide dismutase 1
