Degenerative path

Question 1

What is a common theme of degenerative neuro disease?

Answer 1

protein aggregates that are resistant to degradation via the ubiquitin-proteasome system

histologically recognized as cellular inclusions

Question 2

What is the MC type of AD?

Answer 2

sporadic late onset type

Question 3

What are the three stages of AD?

Answer 3

• early - insidious impairment of higher intellectual fx, alterations in mood and behavior
• later - progressive disorientations, memory loss, loss of math skills and learned motor skills, aphasia
• final - develop profound disability, may become incontinent, mute and or unable to walk

Question 4

What are the two main processes of AD?

Answer 4

• extracellular deposition of amyloid Abeta
  
  • senile plaques
• intracellular accumulation of tau protein
  
  • neurofibrillary tangles

Question 5

this H&E stain shows…

Answer 5

senile plaques

Question 6

What are we looking at?

Answer 6

beta amyloid immunostain

Question 7

What are we looking at?

Answer 7

neurofibrilary tangles - flame shape or globose tangles

Question 8

What are we looking at?

Answer 8

NFT on Bielschowsky stain, commonly found in cortical and other neurons

Question 9

What is seen in about 90% of AD?

this increases the risk of infarcts and leukoencephalopathy

Answer 9

cerebral amyloid angiopathy

• deposition of Abeta amyloid in the walls of small vessels of the brain results in narrowing of the lumen and loss of smooth muscle

Question 10

What is this called? What disease is it seen in?

Answer 10

walnut brain

Pick Disease

Question 11

In AD, when there is compensatory ventricular enlargement after cortical atrophy, this is called…

Answer 11

hydrocephalus ex vacuo

Question 12

What is the prototypical frontotemporal lobar degenerative tauopathy?

What are associations with it?

Answer 12

Pick Disease

‘knife-blade’ atrophy of frontal and temporal lobes (walnut brain), which may be asymmetrical

Question 13

What do I see microscopically in Pick Disease?

Answer 13

• Pick cells (left) - ballooned neurons with dissolution of chromatin
• Pick bodies (right) - tau-positive spherical cytoplasmic inclusions in neuron cell bodies

Question 14

The pathogenesis of PD is…

Answer 14

accumulation and aggregation of alpha synuclein

Question 15

What is the diagnostic hallmark of PD?

What are they immunoreactive for?

Answer 15

Lewy bodies

ubiquitin and alpha-synuclein

Question 16

combo PD and dementia

fluctuating attention and cognition, hallucinations

depression, sleep disorder, and autonomic dysfunction

Answer 16

Diffuse Lewy Body Disease (DLBD)

Question 17

What are we looking at?

Answer 17

DLBD

• sporadic disorder
• brain atrophy, but not as severe as AD
• small inconspicuous Lewy bodies seen throughout the brain
• A large portion of DLBD pts also have AD pathology

Question 18

What genetics go along with huntington’s disease?

Answer 18

autosomal dominant - 100% penetrance

HD gene on 4p16.3 encodes huntington protein

CAG repeat on first exon

higher number of repeats a/w earlier age of development

Question 19

What do we see?

Answer 19

Left - gliosis of HD

right - normal brain

Question 20

On gross morphology of HD, what do we see?

Answer 20

striking atrophy of the caudate nucleus and less so the putamen

small brain, dilation of ventricles

Question 21

What is the MC form of inherited ataxia?

Answer 21

Friedreich Ataxia (FRDA)

Question 22

How does FRDA begin and what is usually the cause of death?

Answer 22

begins in first decade of life with gait ataxia, followed by hand clumsiness and dysarthria

most people die of cardiomyopathy

Question 23

beginning in early childhood and caused by neuronal degeneration, predominately in the cerebellum

a/w development of telangiectasias in the conjunctiva and skin, and immunodeficiency

Answer 23

Ataxia-telangiectasia

Question 24

What is a big clue to dx ALS?

Answer 24

both upper and lower motor neuron ssx

Question 25

What are early ssx of ALS?

Answer 25

asymmetric weakness of hands, manifested as dropping objects and difficulty performing fine motor tasks, cramping and spasticity of arms and legs

Question 26

How would you dx ALS?

Answer 26

clinical picture, electrodiagnostic findings, and muscle biopsy results