Neurodegenerative Diseases SDL

Question 1

What are the general features of neurodegenerative diseases?

Answer 1

• Gray matter diseases (neuron cell bodies)
• Usually an accumulation of protein due to problem with certain mechanism in cell
• Selective injury (clinical findings determined from involved area)
• Results in neuron loss and gliosis (scarring in response to injury)

Question 2

What is the most common cause of dementia?

Answer 2

Alzheimer’s Disease (AD)

Question 3

What is normally the cause of death from Alzheimer’s (AD)?

Answer 3

• Pneumonia (infections)
• Malnutrition

Question 4

Describe the course of Alzheimer’s Disease (AD).

Answer 4

1. Gradual impairment of cognitive function
2. Later disorientation and memory loss
3. Eventual immobilization and muteness

Question 5

What is the histological findings in Alzheimer’s?

Answer 5

• Neurofibrillary tangles and plaques (composed ot tau proteins)
• Result from a cleavage error in β-APP and results in an accumulation of the β-amyloid which forms the plaques/tangles

Question 6

What is another result of β-amyloid accumulation?

Answer 6

Cerebral Amyloid Angiopathy (CAA)

• β-amyloid also accumulates in blood vessel walls which weakens them

Question 7

What are some subsequent changes that occur in the neuron (both axon and body) as a result of Alzheimer’s?

Answer 7

• Formation of paired helical filaments
• Hyperphosphorylated tau
• MAP2 (microtubule associated protein) problems
• Ubiquination
• Neuropil threads

Question 8

What other disease shows neurofibrillary tangles?

Answer 8

Progressive Supranuclear Palsy (PSP) in the brainstem

Question 9

In Alzheimer’s, where in the brain do neurofibrillary tangles start to form?

Answer 9

• Start in hippocampus and spread along components of limbic system
• Eventually involve neocortex

Question 10

Which genes increase chances of developing familial or sporadic Alzheimer’s

Answer 10

• Familial
  
  • β-APP (21)
  • Presenilin-1 (14)
  • Presenilin-2 (1)
• Sporadic
  
  • ApoE4 (19)
  • IL-1A & B (2)

Question 11

(T/F): Essentially all patients with DLB (Dementia with Lewy Bodies) have Parkinson’s.

Answer 11

True. They will have both cortical and substania nigra lewy bodies.

• However, not all Parkinson’s patients have DLB (they might not have cortical LB)

Question 12

What are the characteristics of Progressive Supranuclear Palsy (PSP)?

Answer 12

• Symptoms:
  
  • Vertical gaze palsy
  • Truncal rigidity
• Histology:
  
  • No tau mutations
  • Globose neurofibrillary tangles in globus pallidus, substantia nigra, and dentate nucleus

Question 13

What are the characteristics of Corticobasal Degneration (CBD)?

Answer 13

• Symptoms:
  
  • Extrapyramidal rigidity
  • Alien hand
  • Sensory cortical dysfunction
  • Cognitive decline
• Histology:
  
  • Balooned neurons
  • Tau + astrocytes in motor and premotor cortex, basal ganglia, and substantia nigra

Question 14

What are the symptoms of Parkinsons?

Answer 14

• Tremor (at rest)
• Rigidity (cogwheel)
• Akinesia or bradykinesia (slow movements)
• Postural instability (late)
• Shuffling gate

Question 15

What are the pathological findings in Parkinsons?

Answer 15

• Loss of substantia nigra dopaminergic neurons
• Lewy bodies in substantia nigra (α-synuclein +)
• Loss of neuromelanin (pigment responsible for substania nigra color)
• Associated with other Lewy body disorders

Question 16

What are some other causes of Parkinsonism?

Answer 16

• Drugs (especially neuroleptics)
• Trauma (boxers)
• Other basal ganglia and brainstem diseases

Question 17

Why might neuromelanin be seen microscopically even if a patient has Parkinsons?

Answer 17

• Neuromelanin can remain for sometime in neuropil after neurons have degenerated
• Neuromelanin can still be in the macrophages that are clearing it out

Question 18

What is Multiple System Atrophy (MSA)?

Answer 18

• α-synuclein + neuronal inclusions
• Involvement of cerebellum, pons, medulla, substantia nigra and striatum
• Glial cytoplasmic inclusions, typically oligodendroglial

Question 19

What are the subtypes of Multiple System Atrophy (MSA)?

Answer 19

• MSA-P: Parkinsonism-dominant (striatonigral degeneration)
• MSA-C: Cerebellar dysfunction dominant (olivopontocerebellar atrophy)
• MSA-A: Autonomic dysfunction dominant (Shy-Drager syndrome)

Question 20

What are the characteristics of Huntington’s Disease?

Answer 20

• Large,involuntary movements (chorea)
• Cortical neuron loss and dementia (usually late)
• Trinucleotide repeats (CAG) in huntington gene (Chr 4)
• Atrophy of striate nuclei (cuadate, putamen) and globus pallidus

Question 21

What the characteristics and subtypes of Spinocereballar Degeneration?

Answer 21

• Involves degernation in the cerebellum, spinal cord, and peripheral nerves
• Results in:
  
  • Cereballar and sensory ataxia, spasticity, sensorimotor peripheral neuropathy
  • It is inherited
  • There is neuron loss and gliosis
• Subtypes: Spinocerebllar ataxias (SCA), Friedreich’s ataxia (FA), Ataxia telengiectasia (AT)

Question 22

(T/F): Motor Neuron Disease can involve upper motor neurons, spinal nerve lower motor neurons, or cranial nerve motor neurons.

Answer 22

True.

Question 23

What are the characteristics of ALS?

Answer 23

• Affects middle-aged adults
• Slowly progressive (approx 5 years)
• Loss of anterior horn motor neurons
• Degeneration of lateral corticospinal tracts
• Muscle atrophy/weakness
• Eventual respiratory muscle involvement and death

Question 24

What is Infantile Spinal Muscular Atrophy?

Answer 24

• AKA Werdnig-Hoffman Disease
• A degenerative motor neuron disease that affects spinal muscles in infants (more severe than chronic/adult form)
• Death within one year
• Loss of anterior horn motor neurons