Basal Ganglia Conditions

Question 1

What were the 4 basal ganglia conditions discussed in class?

Answer 1

1) parkinson’s disease
2) progressive supranuclear palsy
3) huntington’s disease
4) wilson’s disease

Question 2

Which part of the basal ganglia is affected in Parkinson’s disease?

Answer 2

substantia nigra

Question 3

Which part of the basal ganglia is affected in wilson’s disease?

Answer 3

putamen nucleus

Question 4

What is parkinson’s disease?

Answer 4

-gradual progressive neurodegenerative disease caused by loss of dopaminergic neurons from the substantia nigra
-more common in men

Question 5

What is the neuron damage progression of Parkinson’s?

Answer 5

-first begins in the lower brainstem and then works its way up (no signs or symptoms yet)
-midstage substantia nigra will result in movement disorders
-final stage reaches cerebral cortex and will result in depression, emotional changes, and dementia with lewy bodies

Question 6

What is the histological hallmark of Parkinson’s disease?

Answer 6

presence of alpha synuclein containing lewy bodies

(alpha synuclein is a protein that is normally used in vesicular transport so when there is an abnormality it will aggregate and cause inclusion bodies)

Question 7

Where are lewy bodies found in neurons in Parksinson’s disease?

Answer 7

-brain stem
-substantia nigra
-cerebral cortex

Question 8

Which disease will have a loss of dopaminergic neurons from the substantia nigra?

Answer 8

Parksinson’s disease

Question 9

What is the clinical triad of Parkinson’s disease?

Answer 9

1) tremor (usually resting tremor)
2) muscle rigidity
3) bradykinesia

***clinical diagnosis requires manifestation of at least 2 of the clinical triad

Question 10

Which disease responds well to L-dopa therapy (precursor for dopamine)?

Answer 10

Parkinson’s disease

note: this just slows the progression, it wont cure it

Question 11

Which tremor is EXCLUSIVE to parkinson’s disease?

Answer 11

pill rolling tremor

Question 12

What are the parkinson’s tremors?

Answer 12

1) resting tremor
-shaking, most noticeable in the hands but can affect arms and legs
-initially asymmetric but often progresses to the other side
-initial side of tremor onset will remain most apparent

2) pill rolling tremor
-type of resting tremor seen in fingers and thumb

Question 13

Parkinson’s muscular rigidity is responsible for….

Answer 13

-severe muscle stiffness (limit range of motion, can lead to dystonia)
-Parkinsonian gait
-stooped posture
-hypophonia (low voice)
-difficulty swallowing
-resistance to passive movement (cogwheel rigidity)

Question 14

Parkinson’s bradykinesia is responsible for…

Answer 14

-slowing of voluntary movement
-difficulty getting out of chair
-Parkinsonian gait
-micrographia (writing progressively gets smaller and smaller)

Question 15

Parkinson’s bradykinesia and muscle rigidity combined is responsible for….

Answer 15

-mask face (facial akinesia, wide eyed, reduced blinking, forced smile)
-parkinsonian gait, aka propulsive gait (forced flexed stooped posture, impaired balance, short shuffling steps, reduced arm swings)

Question 16

What is progressive supranuclear palsy?

Answer 16

-rare aggressive progressive neurodegenerative disease caused by damage to the basal nuclei, periaquaductal gray, cerebellum, and oculomotor nuclei
-males affected 2x more than females
-symptoms similar to parkinson’s but this is more aggressive
-cause is unknown, but it linked to single nucleotide polymorphisms near the tau gene locus (tauopathy)

Question 17

Which condition is this?
-accumulation of neurofibulary tangles in the brain and causes neuronal loss of globus pallidus, subthalamic nucleus, substantia nigra, colliculi, PAG, and dentate nucleus of the cerebellum, as well as the oculomotor nuclei

Answer 17

progressive supranuclear palsy

Question 18

What is the hallmark of progressive supranuclear palsy?

Answer 18

presence of tau containing inclusion bodies in neurons and glia cells

Question 19

What are the clinical features for progressive supranuclear palsy?

Answer 19

similar to parkinson’s:
-muscle rigidity
-bradykinesia
-loss of balance
-unsteady gait
-dementia
-dysphagia

different from parkinson’s:
-vision effected due to loss of vertical gaze bc of lesion on oculomotor nuclei
-neck extended due to nuchal dystonia
-NO TREMORS

Question 20

What is the most unique sign of progressive supranuclear palsy?

Answer 20

loss of vertical gaze due to lesion of the oculomotor nuclei

Question 21

What is huntington’s disease?

Answer 21

-autosomal dominant genetic disorder that codes abnormal synthesis of huntingtin proteins which leads to degeneration of striatal neurons
-its a polyglutamine trinucleotide repeat expansion disease
-during the synthesis of normal huntingtin protein there is a strech of CAG repeats that encodes a polyglutamine
-too many CAG repeats during synthesis of huntingtin protein = huntingtin’s disease (normal is 6-35 repeats, any more results in disease)
-the number of repeats determines the age of onset (more repeats= earlier onset)
-polyglutamine inclusion bodies inside neurons aggregate causing death of neurons
-neuron death found in the corpus striatum and cortical neurons
-will atrophy the caudate nucleus

Question 22

What are the clinical features of huntington’s disease?

Answer 22

chorea:
-damaged striatal neurons leads to dysregulation of the basal ganglia circuitry
-the brain can no longer dampen or modulate motor activity so the patient will have abnormal movement and gait
-often manifested as choreoathetosis (chorea + athetosis)

motor
-motor symptoms typically precede cognitive problems
-choreiform (involuntary jerky movements of all parts of the body and writhing movements of the extremities)

cognitive
-forgetfulness
-difficulty organizing, prioritizing, or focusing on tasks
-difficulty in learning new info
-later stages will have severe dementia

psychiatric:
-depression due to brain injury
-irritable
-social withdrawal

Question 23

What is wilson’s disease?

Answer 23

-an autosomal recessive disorder caused by mutation of a gene, resulting in the liver not being able to release copper into bile
-manifests very young
-mutation in the ATP7B gene impairs binding of copper into ceruloplasmin which is a liver protein that stores and transports copper around the body, so free unbound copper will enter bloodstream instead
-toxic levels of copper accumulate in the liver, eyes, and brain

Question 24

Where do toxic levels of copper accumulate in patients with wilson’s disease?

Answer 24

1st= liver

then the eyes and brain

Question 25

Which disease is this?
-cavitation of the putamen
-classic panda face seen on MRI

Answer 25

wilson’s disease

Question 26

What are the clinical features of wilson’s disease?

Answer 26

-wing beating tremor
-uncoordinated
-chorea or choreoathetosis
-dystonia
-mask like face
-dysphasia + dysarthria
-combo of spastic diplegic gait (scissor) and chorea
-kayser-fleischer rings around the iris