Neurodegenerative Diseases

Question 1

List possible causes of Parkinson’s

Answer 1

age, environment (exposure to manganese, iron, pesticides, well water, rural farming), trauma, emotional stress, repetitive head injury

Question 2

List the symptoms of Parkinson’s

Answer 2

tremor at rest, rigidity of limbs, akinesia, postural problems

Question 3

What is the most common form of Parkinson’s?

Answer 3

idiopathic paralysis agitans

Question 4

How long does it take for PD to progress to rigid akinetic state?

Answer 4

5-10 years

Question 5

Where does neurodegeneration occur in PD?

Answer 5

loss of pigmented dopaminergic neurons in substantia nigra

Question 6

What is drug therapy in PD aimed at correcting?

Answer 6

aimed at correcting imbalance between Ach and dopamine by either increasing supply of dopamine or blocking/lowering Ach levels

Question 7

Differentiate between normal communication between substantia nigra and corpus striatum compared to communication in PD

Answer 7

normally inhibitory DA neurons from substantia nigra act against excitatory Ach in corpus striatum so GABA stays neutral
in PD there is no inhibitory neurons to act against Ach excitation due to loss of DA neurons so GABA increases = muscle rigidity

Question 8

Describe the drugs that form dopamine

Answer 8

Levodopa is the precursor of dopamine and is the major initial drug used for treatment, can cross BBB unlike dopamine and is taken up by DA neurons -> dopamine, however levodopa is sometimes transformed into dopamine prior to crossing BBB reducing effect in brain, combination with carbidopa results in much better delivery across BBB as stops this happening

Question 9

Describe prognosis of PD

Answer 9

near-normal life expectancy, can contribute to other conditions that are sometimes fatal, no cure or way to slow down only management of symptoms, walking and movement can help

Question 10

Compare prevalence of PD to HD in Aus

Answer 10

PD: 250,000
HD: 2160

Question 11

What is the onset age of HD?

Answer 11

30-55y/o

Question 12

List the symptoms of HD

Answer 12

gradual uncontrolled writhing and twisting of muscles in face, trunk, and neck, stumbling, clumsiness, mood swings, personality changes, problems swallowing, speaking and breathing, progressive dementia

Question 13

How is the brain affected in HD

Answer 13

Death of GABAergic neurons, cell loss in basal ganglia, 75% reduction in activity of Glu acid decarboxylase which is responsible for synthesis of GABA, loss of inhibitory brake in DA circuits

Question 14

Differentiate between normal communication between substantia nigra and corpus striatum compared to communication in HD

Answer 14

Dopamine from substantia nigra reaches corpus striatum with Ach as per normal but due to 75% reduction in activity of neurons responsible for synthesis of GABA, it is not produced, since GABA is inhibitory this results in net excitation and uncontrolled motor activity

Question 15

What is the cause of HD

Answer 15

majority (2/3) autosomal dominant genetic mutation, if parent has gene 50% chance child will have HD

Question 16

Compare CAG DNA sequence repetition amount in normal people compared to HD

Answer 16

CAG sequence normally repeats 11-30x, in HD repeats 36-125x

Question 17

Describe drug treatment of HD

Answer 17

no cure, management of unwanted movement by reducing levels of dopamine in key movement circuit using tetrabenazine, haloperidol improves motor function and psychosis

Question 18

Describe prognosis of HD

Answer 18

15-20 years after developing symptoms, death usually from aspiration pneumonia, depression and suicide common

Question 19

Describe motor neuron disease (MND) and the symptoms

Answer 19

progressive, affects motor neurons, very rare, symptoms: muscle cramps, twitching, atrophy, weakness

Question 20

What % of motor neurons estimated to be lost in MND before symptoms become apparent?

Answer 20

> 50%

Question 21

What is the possible cause of MND?

Answer 21

defect in enzyme superoxide dismutase

Question 22

What is the main drug for MND and what does it do to help?

Answer 22

Riluzole may postpone tracheotomy for few months and delay neuronal death