Sheet 6

Question 1

The basal ganglia (site 4) have several functions, such as:

Answer 1

Controlling and regulating

movement

Question 2

What is Parkinson’s disease (PD)?

Answer 2

A neurodegenerative disease marked by a hypokinetic movement disorder that is caused by loss of dopaminergic neurons from the substantia nigra

Question 3

All neurodegenerative diseases are characterized by:

Answer 3

Accumulation of proteins inside the CNS (but they differ in the type of protein and site of deposition) = becomes toxic to the neurons = their death.

Question 4

What is the most common neurodegenerative disease?

Answer 4

Alzheimer’s

Question 5

What is the second most common neurodegenerative disease?

Answer 5

Parkinson’s

Question 6

What is Parkinsonsim?

Answer 6

A clinical syndrome: tremor, rigidity, bradykinesia, and instability.

Question 7

What is the definition of Parkinsonism?

Answer 7

Any damage of dopaminergic neurons, which project from the substantia nigra to the striatum (control of motor activity).

Question 8

What happens to the substantia nigra in Parkinson’s in regards to pigmentation?

Answer 8

It’s original brown color loses its pigmentation

Question 9

Parkinsonism can be induced by:

Answer 9

Drugs such as dopamine antagonists or toxins that selectively injure dopaminergic neurons

Question 10

What is the pathogenesis of PD?

Answer 10

1) Protein accumulation and aggregation, mitochondrial abnormalities, and neuronal loss in the substantia nigra and elsewhere in the brain.
2) Abnormal protein and organelle clearance due to defects in autophagy and lysosomal degradation.

Question 11

What is the diagnostic feature of PD?

Answer 11

Lewy body

Question 12

What are Lewy bodies?

Answer 12

Neuronal inclusions inside the cytoplasm containing α-synuclein, a protein involved in synaptic transmission

Question 13

Most PD cases are __, but some are __.

Answer 13

Sporadic; autosomal dominant (mutation of α-synuclein gene)

Question 14

What color do Lewy bodies in a neuron from the substantia nigra stain?

Answer 14

Pink

Question 15

What do Lewy bodies look like histologically?

Answer 15

Amorphous homogeneous rounded to oval inclusions in the cytoplasm of neurons

Question 16

What is the morphology of PD?

Answer 16

1) Pallor of the substantia nigra and locus ceruleus. (due to loss of pigmentation)
2) Loss of the pigmented neurons in these regions.
3) Gliosis
4) Lewy bodies in neurons (single or multiple, cytoplasmic, eosinophilic, round to elongated
inclusions)
5) Lewy neurites
6) Immunohistochemical staining for α-synuclein (for subtle lewy bodies).
7) With progression changes can appear in: medulla, pons, amygdala, and the cerebral cortex (+Lewy body dementia LBD).
8) Lewy body dementia LBD

Question 17

What are Lewy neurites?

Answer 17

Dystrophic neurites that also contain aggregated α-synuclein

Question 18

What do α-synuclein look like under the microscope?

Answer 18

Appear brown in color

Question 19

What is Lewy body dementia LBD?

Answer 19

With involvement of the cerebral cortex, there is typically dementia (loss of cognitive features, memory disturbances, behavioral changes) in addition to the movement disorder.

Question 20

True or false:
Parkinson’s itself does not affect the cognitive features without progression to
the cerebral cortex.

Answer 20

True

Question 21

The progression of PD is:

Answer 21

1) Gradual (over 10 to 15 years (slow downhill))
2) Eventually produces severe motor slowing or near immobility
3) Death due to aspiration pneumonia or trauma from falls caused by postural instability (gait disorder).

Question 22

What is the treatment of PD?

Answer 22

1) Initially responds to L-DOPA, but this treatment does not slow disease progression or reverse morphologic findings.(doesn’t affect protein aggregation or neuron loss).
2) Deep brain stimulation

Question 23

Does L-DOPA help in the long-run?

Answer 23

No; over time, L-DOPA becomes less effective (causes dependence).

Question 24

What are the symptoms of PD?

Answer 24

1) Tremor
2) Slowed movement (bradykinesia)
3) Rigid muscles
4) Impaired posture and balance
5) Loss of automatic movements
6) Speech changes
7) Writing changes
8) Diminished facial expressions (Masked faces)
9) Stooped posture and balance problems
10) Slow voluntary movement
11) Festinating gait= progressively shortened accelerated steps.

Question 25

Describe the bradykinesia (slowed movement) of PD.

Answer 25

1) Steps may become shorter
2) Difficult to get out of a chair
3) Drag their feet as they try to walk (Shuffling, festinating gate)

Question 26

Describe the tremors of PD.

Answer 26

Involuntary shaking, usually at rest and disappears with movement. Begins in a limb, often in the hands or fingers. Patients might rub their thumb and forefinger back-and-forth ( pill-rolling tremor.)

Question 27

Describe the loss of automatic movements of PD.

Answer 27

Decreased ability to perform unconscious movements, including blinking, smiling (masked face), or swinging arms during walking

Question 28

Describe the speech changes of PD.

Answer 28

Patients might speak softly, quickly, slur, or hesitate before talking

Question 29

What is Huntington’s disease characterized by?

Answer 29

1) Hypermotility or mobility

2) Choreiform dancing movements of the whole body (from the head to the limbs and trunk) called chorea

Question 30

What is the cause of Huntington’s?

Answer 30

Degeneration of the striatum (caudate and putamen) as a result of
protein accumulation.

Question 31

Huntington’s mode of inheritance is:

Answer 31

Autosomal dominant (NOT sporadic)

Question 32

What is the progression of Huntington’s?

Answer 32

Gradual, death after an average of 15 years

Question 33

Do cognitive symptoms occur in Huntington’s?

Answer 33

Yes, early on (forgetfulness and thought and affective disorders, severe
dementia).

Question 34

What is the pathogenesis of Huntington’s?

Answer 34

CAG trinucleotides repeat expansions in huntingtin protein gene located on 4p16.3 (Polyglutamine) (hundreds of repeats)

Question 35

What do larger numbers of repeats result in?

Answer 35

Earlier-onset disease

Question 36

What happens genetically in Huntington’s?

Answer 36

Mutant protein is subject to proteolysis = fragments form large intranuclear aggregates (not in the cytoplasm) = toxic = loss of neurons

Question 37

What is the age of onset in Huntington’s and what does it depend on?

Answer 37

40-50 years; related to the length of CAG repeats (more repeats = earlier age of onset)

Question 38

What is the morphology of Huntington’s?

Answer 38

1) Atrophic brain
2) Striking atrophy of the caudate nucleus and the putamen
3) Atrophy of globus pallidus
4) Dilated lateral and third ventricles secondarily (like Alzheimer’s but at small age)
5) Severe loss of neurons from affected regions of the striatum + gliosis
6) Spiny neurons that release γ-aminobutyric acid (GABA), enkephalin, dynorphin, and substance P are especially sensitive, disappearing early.
7) Intranuclear inclusions (aggregates of ubiquitinated huntingtin protein)