Demyelinating CNS Diseases and Degenerative CNS Diseases

Question 1

What is the incidence of Multiple Sclerosis?

Answer 1

• 20-30 years
• More common in Women

Question 2

What are the favored sites for demyelination in MS?

Answer 2

• Optic Nerve
• Brain Stem
• Periventricular Areas

Question 3

What are the early findings that manifest in MS? (5)

Answer 3

• Weakness of the lower extremities
• Visual disturbances
• Retrobulbar pain
• Sensory disturbances
• Possible loss of bladder control

Question 4

What is the Charcot Triad, that MS may manifest as?

Answer 4

• Nystagmus (involuntary eye movement)
• Intention Tremor
• Dysarthria (“scanning speech”)

Question 5

What are the Oral Manifestations of MS, reported to occur in 2-3% of thoose affected, and may serve as the first presenting symptoms of MS?

Answer 5

• Pts face may develop paresthesia
• Weakness of muscles of facial expression (periorbatal) can undulate in a wave-like manner - myokymia (bag of worms)
• Trigeminal neuralgia is 400x more likely among individuals with MS than the general population

Question 6

What is the cause of Guillain-Barre Sx (acute inflammatory demyelinating polyradiculopathy)?

Answer 6

• Most common form of acute neuropathy
• Autoimmune-mediated demyelination of peripheral nerves
• Occurs 2-4 weeks after a viral infection, immunization, or allergic rxn

Question 7

Who has the highest incidence of Guillain-Barre Sx?

Answer 7

young adults

Question 8

How does Guillain-Barre Sx manifest clinically?

Answer 8

• Motor neuropathy
• Ascending muscle weakness and paralysis
  
  • Beginning in the lower part of the lower extremities and ascending upward
• Respiratory failure and death may occur, but most pts recover completely - remyelination in 3-4 months

Question 9

What is the fundamental abnormality in Alzheimer’s Disease?

Answer 9

• Deposition of beta amyloid peptides
• Which are dervided through the processing of amyloid precursor protein (APP)
  
  • APP - results in the generation of AB and the formation of amyloid fibrils

Question 10

What is seen in the hippocampus, amygdala, and neocortex of pts with AD, that contains a beta amyloid peptide core?

Answer 10

Neuritic (senile) plaques

Question 11

In the Etiology of AD, what promotes AB generation and deposition?

Answer 11

ApoE

Question 12

What encodes an ApoE isoform and has a strong influence on the risk of developing AD?

Answer 12

A genetic locus on chromosome 19

Question 13

The dosage of what, increases the risk of AD and lowers the age of onset of the disease?

Answer 13

E4 allele

Question 14

What happens when beta amyloid peptides aggregate?

Answer 14

• Directly neurotoxic
• Synaptic dysfunction - blocking of long-term potentiation
• Elicit an inflammatory response from microglia and astrocytes
  
  • Assist in clearance (good)
  • Stimulate the secretion of mediators that cause damage to neurons (bad)

Question 15

What are neurofibrillary tangles (NFTs)?

Answer 15

Abnormal tangles of insoluble cytoskeletal-like hyperphosphorylated tau filaments (paired helical) that form within the cytoplasm of neurons in the brain

• Mutations in the tau gene (encodes for tau) can be found in pts with AD

Question 16

What is a clinical finding in AD?

Answer 16

• Choline acetyltransferase Deficiency
  
  • the brain content of the enzyme and its product, acetylcholine is decreased
    
    • Ach plays a role in learning
  • Especially in: Cerebral cortex and Hippocampus

Question 17

What are the Gross Pathologic Findings seen in AD?

Answer 17

• Cortical atrophy - widening of the cerebral sulci
• Hydrocephalus ex vacuo
  
  • compensatory ventricular enlargement 2^o to loss of parenchyma and reduced brain volume

Question 18

What AD finding correlates best with the degree of dementia?

Answer 18

of NFTs

Question 19

What are the biochemical markers seen in AD that have been correlated with the degree of dementia?

Answer 19

• Loss of choline acetyltransferase
• Amyloid burden

Question 20

Parkinson’s Disease is a slowly progressive debilitating, degenerative disorder of what?

Answer 20

Basal Ganglia

Question 21

What are the Etiologies of secondary (aquired) PD (25%)?

Answer 21

• Familial inhereted
• Repeated Trauma (pugilistic PD)
• Dopamine antagonists - MPTP
• Shy-Drager Syndrome: autonomic degeneration and orthostatic hypotension with parkinsonism

Question 22

What is the Pathogenesis of PD?

Answer 22

• Degeneration of pigmented dopaminergic neurons of the substantia nigra
• Reducing the amount of dopamine in the corpus striatum
  
  • Loss of at least 60% before clinical symptoms occur
• Lewy Bodies - surviving cells in the substantia nigra contain eosinophilic spherical inclusions, which contain cytoskeletal filaments

Question 23

PD with dementia (PDD) would be the diagnosis when?

Answer 23

dementia onset is > 1 yr after the onset of PD

Question 24

DLB would be the diagnosis when?

Answer 24

Cognitive/dementia symptoms begin at the same time or within 1 yr of PD symptoms

Question 25

What is Huntington’s Disease characterized by?

Answer 25

• Delay of clinical abnormalities until age 30-40
• Increased #s of CAG trinucleotide repeats within the HD gene on the short arm of chromosome 4

Question 26

ALS is a progressive neurodegenerative ds of unknown etiology characterized by loss of motor neurons which is most striking in the …

Answer 26

• Anterior horn cells of spinal cord but may involve cranial motor nuclei
• Loss of anterior horn cells leads to muscle atrophy

Question 27

What is the cause of familial (5%) cases of ALS?

Answer 27

Mutation of SOD1 gene