Neurodegenerative Diseases

Question 1

How are neurodegenerative diseases typically/traditionally classified?

Answer 1

• According to clinical presentation
• Alzheimers
○ Early memory and visuospatial problems
• Frontotemporal dementia
○ Early behavioral, executive and language problems
• Parkinsons
○ Tremor, rigidity, bradykinesia
• Lewy
○ Early parkinsonian features, psychosis, fluctuating consciousness
• Progressive supranuclear palsy
○ Bradykinesia, rigidity, falls, abnormal vertical eye movements
• Amyotrophic lateral sclerosis
○ Weakness and atrophy, fasciculations, and the combination of both upper and lower motor neuron signs
• Huntingtons
○ Dementia, depression, chorea
• Creutzfeldt-jakob
○ Rapidly progressive dementia with myoclunus

Question 2

What are the classic signs of CJD?

Answer 2

• Creutzfeldt-jakob

○ Rapidly progressive dementia with myoclunus

Question 3

What are the classic signs of huntington’s?

Answer 3

• Huntingtons

○ Dementia, depression, chorea

Question 4

What are the classic signs of ALS?

Answer 4

• Amyotrophic lateral sclerosis

○ Weakness and atrophy, fasciculations, and the combination of both upper and lower motor neuron signs

Question 5

what are the classic signs of progressive supranuclear palsy?

Answer 5

• Progressive supranuclear palsy

○ Bradykinesia, rigidity, falls, abnormal vertical eye movements

Question 6

what are the classic signs of lewy body disease?

Answer 6

• Lewy

○ Early parkinsonian features, psychosis, fluctuating consciousness

Question 7

what are the classic signs of parkinsons?

Answer 7

• Parkinsons

○ Tremor, rigidity, bradykinesia

Question 8

what are the classic signs of alzheimers?

Answer 8

• Alzheimers

○ Early memory and visuospatial problems

Question 9

what are the classic signs of frontotemporal dementia?

Answer 9

• Frontotemporal dementia

○ Early behavioral, executive and language problems

Question 10

Neurodegenerative diseases seem to be variations on a theme. What is the theme?

Answer 10

• Theme - spontaneous death of neuronal populations
  
  • The location of the neurons determine the clinical presentation
  • Remember that neuronal location is tied to neuronal function

Question 11

What protein is implicated in frontotemporal dementia and progressive supranuclear palsy?

Answer 11

• Abnormal tau metabolism

* Neurofibrillary tangles?

Question 12

Synuclein is a protein that when you see it you should think…?

Answer 12

• Parkinsons

* Lewy body diseases

Question 13

Ubiquitin in the context of neurodegenerative disease makes you think…?

Answer 13

• ALS

* Amyotrophic lateral sclerosis

Question 14

Disturbances in ach neuronal transmission makes you think:

Answer 14

• Alzheimers and lewy body

* Though there are other pathways disturbed in each of the neuorodegen diseases

Question 15

Serotonergic dysfucntion makes you think:

Answer 15

• Frontotemporal dementia

* Though there are other pathways disturbed in each of the neuorodegen diseases

Question 16

Disturbances in dopamine transmission makes you think:

Answer 16

• Parkinsons and lewy body

* Though there are other pathways disturbed in each of the neuorodegen diseases

Question 17

What are the neuropathology findings of: Alzheimers

Answer 17

• Amyloid plaques and neurofibrillary tangles
• Dx requires the presence of both of these changes on pathologic examination
• Location is cortexa nd hippocampus with sparing of deeper structures
Gross - diffuse atrophy

Question 18

What are the neuropathology findings of: FTD - frontotemporal dementia

Answer 18

• This is less of a single disease and more of a collection of pathology
  
  • Some have neurofibrillary tangles
  • Others have predominately ubiquitin inclusions
  • Some have tau reactive intra-neuronal inclusion
  • Some have CDP-43 deposition
  • Many have no findings at autopsy - “dementia lacking distinct histological features”

Question 19

What are the neuropathology findings of: Huntingtons

Answer 19

• Neurodegeneration has a predilection for the caudate nucleus
  
  • Produces a characteristic pattern of atrophy that can be seen with neural imaging by CT or MRI