Basal Ganglia Conditions Flashcards
What were the 4 basal ganglia conditions discussed in class?
1) parkinson’s disease
2) progressive supranuclear palsy
3) huntington’s disease
4) wilson’s disease
Which part of the basal ganglia is affected in Parkinson’s disease?
substantia nigra
Which part of the basal ganglia is affected in wilson’s disease?
putamen nucleus
What is parkinson’s disease?
-gradual progressive neurodegenerative disease caused by loss of dopaminergic neurons from the substantia nigra
-more common in men
What is the neuron damage progression of Parkinson’s?
-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
What is the histological hallmark of Parkinson’s disease?
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)
Where are lewy bodies found in neurons in Parksinson’s disease?
-brain stem
-substantia nigra
-cerebral cortex
Which disease will have a loss of dopaminergic neurons from the substantia nigra?
Parksinson’s disease
What is the clinical triad of Parkinson’s disease?
1) tremor (usually resting tremor)
2) muscle rigidity
3) bradykinesia
***clinical diagnosis requires manifestation of at least 2 of the clinical triad
Which disease responds well to L-dopa therapy (precursor for dopamine)?
Parkinson’s disease
note: this just slows the progression, it wont cure it
Which tremor is EXCLUSIVE to parkinson’s disease?
pill rolling tremor
What are the parkinson’s tremors?
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
Parkinson’s muscular rigidity is responsible for….
-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)
Parkinson’s bradykinesia is responsible for…
-slowing of voluntary movement
-difficulty getting out of chair
-Parkinsonian gait
-micrographia (writing progressively gets smaller and smaller)
Parkinson’s bradykinesia and muscle rigidity combined is responsible for….
-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)
What is progressive supranuclear palsy?
-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)
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
progressive supranuclear palsy
What is the hallmark of progressive supranuclear palsy?
presence of tau containing inclusion bodies in neurons and glia cells
What are the clinical features for progressive supranuclear palsy?
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
What is the most unique sign of progressive supranuclear palsy?
loss of vertical gaze due to lesion of the oculomotor nuclei
What is huntington’s disease?
-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
What are the clinical features of huntington’s disease?
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
What is wilson’s disease?
-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
Where do toxic levels of copper accumulate in patients with wilson’s disease?
1st= liver
then the eyes and brain
Which disease is this?
-cavitation of the putamen
-classic panda face seen on MRI
wilson’s disease
What are the clinical features of wilson’s disease?
-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
