Pathology - Neurodegenerative Diseases and Demyelinating Diseases

Question 1

Which neurodegenerative disorder is caused by a virus in immunocompromised patients? Which virus is it? Which cell types in the CNS are destroyed?

Answer 1

Progressive multifocal leukoencephalopathy is caused by JC virus, a type of polyomavirus. Oligodendrocytes are killed.

Question 2

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?

Answer 2

Correcting hyponatremia too quickly can cause central pontine myelinolysis –> locked in syndrome.

See photo - note the lack of blue (myelin) in the pons.

Question 3

In what general geographic region is the prevalence of MS highest?

Answer 3

Northern latitudes

Question 4

At what age does MS most often present?

Answer 4

Between 20 and 30 years old

Question 5

What criteria is used to make the diagnosis of MS clinically?

Answer 5

Two lesions separated by time and space

Question 6

What CSF findings are indicative of a diagnosis of MS?

Answer 6

Oligoclonal bands (of IgG)

Question 7

Specifically where in the brain do MS lesions tend to occur? How can you tell the difference between new and old lesions?

Answer 7

The lesions occur in periventricular areas.

New ones will ring-enhance w/ gadolinium, while old ones appear as areas of demyelination.

Question 8

Identify the type of brain matter indicated by the arrows. What is your Dx based on this histo slide?

Answer 8

Bottom left is white matter, bottom right is gray matter. The big white patch is an area of demyelination from MS.

Question 9

What’s up wit it?

Answer 9

MS lesion

Question 10

What is tumefactive multiple sclerosis?

Answer 10

When someone has MS with a fucking huge lesion that has mass effect, edema, or ring enhancement.

Question 11

What is your differential diagnosis for this?

Answer 11

MS or progressive multifocal leukoencephalopathy (its PML but Rendi said you’ll never have to differentiate the two via histology)

Question 12

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?

Answer 12

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

Question 13

Which virus is thought to trigger the development of MS via molecular mimicry?

Answer 13

EBV

Question 14

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?

Answer 14

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

Question 15

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?

Answer 15

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

Question 16

What are the inheritable mutations that can cause early-onset Alzheimer’s?

What genes confer greater risk for developing sporadic Alzheimer’s?

Answer 16

Early onset: Presinilin 1 and 2 genes

Sporadic: e4 allele of apolipoprotein-E = greater risk (e2 is protective!)

Question 17

Why do people w/ Down syndrome have a greater risk for developing Alzheimer’s?

Answer 17

The gene for the APP protein is on chromosome 21

Question 18

What is the most noticeable gross pathologic finding of a brain from a patient with advanced Alzheimer’s?

Answer 18

Cortical atrophy, most extensively in the frontal, temporal, and parietal lobes

Question 19

WTF is this, what is it made out of, and what disease is it seen in?

Answer 19

Amyloid plaque, made ouf ot A-beta amyloid, seen in Alzheimer’s

Question 20

This is from a brain. What is your Dx? What sequelae are associated with this?

Answer 20

That is amyloid (apple-green birefringence under polarized light).

Amyloid deposition in vessels weakens them -> risk for cerebral hemorrhage

Question 21

Name three major histopathological features of Alzheimer’s disease and what each is made out of.

Answer 21

Amyloid plaques made from A-beta amyloid

Neurofibrillary Tangles made out of Tau protein

Neuronal loss

Question 22

This is from a brain. What it is? What is it made of?

Answer 22

Neurofibrillary tangle (tau protein)

Question 23

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?

Answer 23

Frontotemporal dementia (aka Pick’s disease)

Round aggregates of tau protein are seen in cortical neurons

Question 24

What is your Dx?

Answer 24

Frontotemporal dementia (Pick’s)

Question 25

How quickly do prion-mediated encephalopathies progress?

Answer 25

Really fucking quickly

Question 26

What histopathologic feature is found in Creutzfeldt-Jakob Disease (CJD)? What is the form of prion that is infectious?

Answer 26

Spongiform change in the cerebral cortex. PrP^sc form is the bad one

Question 27

What are the five major clincal features of Parkinson’s disease?

Answer 27

TRAPS:

Tremor (pill-rolling tremor at rest)

Rigidity (cogwheel)

Akinesia/bradykinesia

Postural instability

Shuffling gait

Question 28

What is the structural cause of Parkinson’s disease?

Answer 28

Loss of dopaminergic neurons in the substantia nigra.

Question 29

What is a histopathologic feature of Parkinson’s disease? What are these made out of?

Answer 29

Lewy bodies in the midbrain - made of alpha-synuclein

Question 30

What it is? What disease(s) is this seen in?

Answer 30

Lewy bodies seen in Parkinson’s or Lewy Body Dementia

Question 31

What differentiates Lewy Body Dementia from Parkinson’s both clinically and histopathologically?

Answer 31

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.

Question 32

Regarding Huntington’s disease…

Describe the inheritance pattern and important details regarding genetics (chromosome, nucleotides, paternal/maternal inheritance differences).

Describe the clinical features.

Answer 32

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

Question 33

What portions of the spinal cord are most often damaged in ALS? What enzymatic defect is associated with ALS?

Answer 33

Lateral corticospinal tract and anterior horn. Superoxide dismutase 1