Lecture 5: Basal Ganglia Disorders Flashcards
Basal ganglia disorder
Movement disorders in basal ganglia dysfunction range from hypokinetic to hyperkinetic
Differences in abnormal movements are due to dysfunction in specific parts of basal ganglia, pedunculopontine tegmental nucleus (PPN), and midbrain locomotor region
Inhibit motor thalamus, PPN, and MLR; excessive inhibition results in hypokinetic disorders, and inadequate inhibition results in hyperkinetic disorder
What is the most common hypokinetic disorder?
* what causes hypokinetic disorders?
Parkinsons disease
Caused by excessive inhibiion in the basal ganglia
What are our 4 hyperkinetic disorders?
* What are hypoerkinetic disorders due to?
disorders:
* Huntingtons disease
* Dystonia
* Tourette’s disorder
* Some times of cerebral palsy
Due to inadequate inhibiton in the basal ganglia
To produce voluntary movement, the sequence of pathway activation in the cortico-basal ganglia-thalamic circuit is as follows
- The stop (hyperdirect) pathway suppresses ongoing movement
- The Go (direct) pathway facilitates specific mvoement while simultaneously the No-Go (indirect) pathway supresses competing movements
The stop, go and no-go pathways all converage on the output nucleus (globus pallidus internus- GPi) –> GPi inhibits the motor thalamus –> motor thalamus then excites the motor areas of the cerebral cortex –> cerebral cortex excites motor neurons in brainstem and spinal cord
* In hypo/hyper kinetic disorders the pathways are abnormal
Which pathway supresses ongoing movements
The Top (hyperdirect) pathway
Which pathway facilitates specific movements?
The Go (direct)
Which pathway works simulatneously with the go pathways to supress competing mvoements?
No-Go
Does the basal ganglia have a direct impact on lower motor neurons?
No, think about where it is, its not connected to any spinal nerves
Functionally, the motor loop regulates 3 activities through 3 pathways. What are the 3 pathways
1) Voluntary muscle actviity
2) Postural and girdle muscle activity
3) Walking (stepping pattern generators)
Knowledge check: which basal ganglia pathway supresses ongoing movement?
Stop
Progressive hereditary disorder characterized by annormalities of movement, personality disturbances and dementia
Huntingtons
Huntingtons is also called huntington chorea
* Choreic moevment = breif, purposeless, involuntary and random
Does huntingtons start in proximal and distal extremtities?
* what are the movements like?
* How long is the disease course
Distal –> Proximal
Movements are ballistic
progresses to bradykinesia, dystonia, rigiditify and ataxia
Disease course ~ 20 years, includes cognitive impairment, fatal
Huntingtons is rare
may begin at any time after infancy byt usually starts in middle age
25% have disease of late onset, which is defined as onset of motor symptoms after the age of 50
Almost always a hx of aprent having HD
50% risk of passing to child
Autosomal dominant, genetic marker, if you have the gene you will develop HD
No cure, etheical dilemma for testing prior to symptom onset
What in the brain changes w/ huntingtons? (what is enlarged what is atrophyed)
volume of brain decreases by how much
Ventricles enlarged as a result of atrophy of adjacent basal ganglia (specifically the caudate and putamen = striatum)
Excessive loss of medium sized neurons
20% volume of brain loss
white matter degereneration in frontal cortex (what causes personality changes)
Other subtle changes in crotex and cerebellum
Is huntgintons hyper or hypo kinetic
Which 3 neurotransmitters is there a decrease in w/ this disease? What two increase?
Hyper
Reduction ins:
1) GABA
2) Acetylcholine
3) Metenkephalin
Increase in
1) Dopamine
2) Norepinephrine
In huntingtons
abrnomal balance of basal ganglia and thalamic inhibition/excitation response results in lack of smooth , controlled movements
* final result of activity in the stop pathway is powerful inhibition of the motor thalamus - well if this is unable to be inhibited the person will have uncontrolled movements, which is what happens in huntingtons
Excess dopamine may lead to overexcitation of thalamocortical pathway (leads to chorea type mvoements)
Later - “opposite” happens, resultant rigidity and bradykinesia
So it flips - start fast and spatistic then rigid and slow
End stages - severe neuronal losss, cell death in BG
Knowledge check: Which neurotransmitter is excess in huntingtons
* Norepi/Dopamine
Chorea = greek word for dance
* people in huntingtons have uncontrollable movement
early in HD - may not show signs and symptoms, choeric movements are often integrated into purpuseful movement - like walking and have a small on in leg from already contracting muscles
Later the choreic movements are incerased by mental concentration, emotional stimuli, performance of complex tasks, and walking
* so essentially when they’re stressed out they’ll have more
Probslems w/ voluntary movement may be detected w/ tests for dysdiadochokinesia
in early cases what happens to m strength w/ HD?
What happens to tone w/ the progression of disease?
What happens to DTR’s?
Nothign its fine
* eventually may be affected by bradukinesia or general motor disturbance
* its more a motor contorl thing than strength (putting it all together)
Tone becomes rigid
* Normal –> rigid (because everything becomes rigid)
DTR’s = normal
Eye movements are affected in HD and indicate CNS abnormality
* What are saccades
* What is smooth pursuit
Saccades - rapid movement of the eyes from one target to another in order to move the visual focus rapidly to different objects, patient unable to excute this
Velocity of eye movement, undershooting, latency in initiation of movement
Gaze fixation - patient unable to focus on something w/o the intrustion of small saccadic movements
Smooth pursuit - tracking of the eye to follow a moving object, patient unable to do this w/o jerky saccadic movements
What is gait like w/ HD?
* early (2)
* Later
Wide-Based (when chorea is dominant)
Staggering (when chorea is dominant)
Later, may present with bradykinesia and hypertonicity therefore gait will be slow stiff and understand
Dysarthria happens in HD. What is this
decrease in the rate and rhythm of speech
* Mild initially, progresses to unintelligible speech, linguistic inabilitis occur, can lead to becoming mute before motor disabiltiy is severe
Dysphagic occurs w/ HD. What is this
Abnormalities swallowing, can lead to chocking and asphyxoa
Cachexia occurs w/ HD what is this
muscle wasting w/ wt loss
KNOW: in HD sleep disorders become progressive, however, choreic movements are reduced in the deepest part of sleep
Urinariy incontience also occurs w/ HD
* Could be releated to cognitive impairment, depression, decreased mobility, or hyperreflexia of the msucles that control urine output
* UTI’s
What happens first in HD motor symptoms of cognitive impairements?
Cognitive impairements happen first
* impairements in information processing speed, attention, executive function and memory retrieval
* Limited insight into their deficits (because they are cognitively impaired) - thiis makes management more difficult for carefivers and families
* Difficulty w/ organization, planning, and sequencing
* Visuosptatial deficits, impaired judgement and ideomotor apraxia ( the inability to perform previously learned tasks despite intact elementary motor function)
Increase loss of awareness = Increase disease severity
w/ HD: Neuropsychologic and psychiatric disorders
* This can happen early (that cognitive comes early)
* Personality and behavior changes, such as irritability, apathy, depression, decreased work perforamnce, violence, impulsivity and emotional lability
* OCD, emotional regulation issues, affective disorders
Knowledge check: w/ HD cogntive impairement is typically deteced b4 motor symptoms
MRI w/ HD will show atrophy of what
Striatum (combination of 2 basal ganglia)
Differential diagnosis = degenerative, systemic, drug related conditions
2 medications for HD
Tetrabenazine
deuterabenazine
not going to need to know these
* they dont cure the disease
Surgical proocedures - remove parts of BG, deep brain stimuation stem cells = mixed reults
* dont work well
Younger people aged 15-40 were expierence a more or less severe form of the disease?
More severe than those who get it in 50s and 60s
* in this case its better to be older when you get it
The advance of the disease is slow, w/ death occuring 15-20 years following onset
Survival into 80s is uncommon, and persons living past 90 have been recorded
age at onset and age at death frequently show a familiar correlation
Clinicopathologic studies demonstrate a strong inverse correlation between age at onset and the severity of striatal degeneation
* again worse to get it when older
Increasing disability from involuntray movements and mental changes often results in death from intercurrent infection
Suicide accounts for approx 6% of deaths and 25% of persons w/ hd had at least 1 suicude attempt
A note on other hyperkinetic disorders - dystonia
Genetic usually nonprogressive movement disorders are characterized by involuntary sustained muscle contractions, causing abnormal posture, twisting and repetitive movements
Often increases during activity and emotional stress and completely vanishes during sleep
Tremor is frequently associated w/ dystonia
* so they can get tremors
Cervical spin (spasmodic toricollis)
* neck can be super tight
Other areas: limbs, hands, eyes, face