Lecture 5: Basal Ganglia Disorders

Question 1

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

Question 2

What is the most common hypokinetic disorder?
* what causes hypokinetic disorders?

Answer 2

Parkinsons disease

Caused by excessive inhibiion in the basal ganglia

Question 3

What are our 4 hyperkinetic disorders?
* What are hypoerkinetic disorders due to?

Answer 3

disorders:
* Huntingtons disease
* Dystonia
* Tourette’s disorder
* Some times of cerebral palsy

Due to inadequate inhibiton in the basal ganglia

Question 4

To produce voluntary movement, the sequence of pathway activation in the cortico-basal ganglia-thalamic circuit is as follows

1. The stop (hyperdirect) pathway suppresses ongoing movement
2. 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

Question 5

Which pathway supresses ongoing movements

Answer 5

The Top (hyperdirect) pathway

Question 6

Which pathway facilitates specific movements?

Answer 6

The Go (direct)

Question 7

Which pathway works simulatneously with the go pathways to supress competing mvoements?

Answer 7

No-Go

Question 8

Does the basal ganglia have a direct impact on lower motor neurons?

Answer 8

No, think about where it is, its not connected to any spinal nerves

Question 9

Functionally, the motor loop regulates 3 activities through 3 pathways. What are the 3 pathways

Answer 9

1) Voluntary muscle actviity
2) Postural and girdle muscle activity
3) Walking (stepping pattern generators)

Question 10

Knowledge check: which basal ganglia pathway supresses ongoing movement?

Answer 10

Stop

Question 11

Progressive hereditary disorder characterized by annormalities of movement, personality disturbances and dementia

Answer 11

Huntingtons

Question 12

Huntingtons is also called huntington chorea
* Choreic moevment = breif, purposeless, involuntary and random

Question 13

Does huntingtons start in proximal and distal extremtities?
* what are the movements like?
* How long is the disease course

Answer 13

Distal –> Proximal

Movements are ballistic

progresses to bradykinesia, dystonia, rigiditify and ataxia

Disease course ~ 20 years, includes cognitive impairment, fatal

Question 14

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

Question 15

What in the brain changes w/ huntingtons? (what is enlarged what is atrophyed)

volume of brain decreases by how much

Answer 15

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

Question 16

Is huntgintons hyper or hypo kinetic

Which 3 neurotransmitters is there a decrease in w/ this disease? What two increase?

Answer 16

Hyper

Reduction ins:
1) GABA
2) Acetylcholine
3) Metenkephalin

Increase in
1) Dopamine
2) Norepinephrine

Question 17

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

Question 18

Question 19

Knowledge check: Which neurotransmitter is excess in huntingtons
* Norepi/Dopamine

Question 20

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

Question 21

in early cases what happens to m strength w/ HD?

What happens to tone w/ the progression of disease?

What happens to DTR’s?

Answer 21

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

Question 22

Eye movements are affected in HD and indicate CNS abnormality
* What are saccades
* What is smooth pursuit

Answer 22

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

Question 23

What is gait like w/ HD?
* early (2)
* Later

Answer 23

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

Question 24

Dysarthria happens in HD. What is this

Answer 24

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

Question 25

Dysphagic occurs w/ HD. What is this

Answer 25

Abnormalities swallowing, can lead to chocking and asphyxoa

Question 26

Cachexia occurs w/ HD what is this

Answer 26

muscle wasting w/ wt loss

Question 27

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

Question 28

What happens first in HD motor symptoms of cognitive impairements?

Answer 28

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

Question 29

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

Question 30

Knowledge check: w/ HD cogntive impairement is typically deteced b4 motor symptoms

Question 31

MRI w/ HD will show atrophy of what

Answer 31

Striatum (combination of 2 basal ganglia) Differential diagnosis = degenerative, systemic, drug related conditions

Question 32

2 medications for HD

Answer 32

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

Question 33

Younger people aged 15-40 were expierence a more or less severe form of the disease?

Answer 33

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

Question 34

Question 35

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

Question 36

**Knowledge check: Which prognosis is the best for disease progression in HD** * Being older leads to a better prognosis

Question 37

Is parkinsons a hypo or hyperkinetic disorder?

Answer 37

Hypo

Question 38

Disease that is progressive of the CNS, charaterized by rigidity, tremor, bradykinesia and postural instability. Characterized by the loss of midbrain dopamine neurons and presence of lewy body inclusions * What does it normally begin and waht is the course of the disease?

Answer 38

Prkinsons disease usually begins in the 5th or 6th decade of life and worsens over 10-20 years Parkinsonian features can be manifested as part of other disease affecting the CNS, such as atherosclerosis, ALs and HD * So other disease can look like it Brain atrophy affecting BG structures can lead to: multiple system atrophy, progressive supranuclear palsy, corticobasal ganglionic degeneration and diffuse Lewy body disease

Question 39

Parkinsons: Second most common neurodegenreative disorder in the US (1 = alzheimer's) Parkinsonism affects more than 800,000 adults in the US, w/ prevalence rates of 350 per 100,000 adults * 42% releated to parkinsons (parkinsons features dont mean they have parkinsons) Higher artes among white americans and europeans 1.4 times more frequent in men than women becomes increasinly common w/ advancing age * so maybe there is something due to neuronal vulnerability

Question 40

exercising keeps the CNS healthy

Question 41

What part of the brain is struggling in parkinsons? * what loop is involved

Answer 41

Basal ganglia is affected Motor loop is involved: Motor loop that determines the intitation and scaling of motor activity derives its input from the premotor, motor, and somatosensory corticies. * This is the process of preparation for fourthcoming movement, and when disrupted it can cause a reduction in size and speed of the movement * people intend to move at normal aplitudes and velocity, but the motor loops just isnt working well so we have to cue this movement w/ external thigns (cueing to move big) Basal ganglia cerebral cortex interactions disrupted due to abnormal BG The pathologic hallmark is the degerenation of a nucleus that is part of the basal ganglia, the substantia nigra - ability to produce dopamine is list

Question 42

What is the motor loop

Answer 42

Motor loop that determines the intitation and scaling of motor activity derives its input from the premotor, motor, and somatosensory corticies. * This is the process of preparation for fourthcoming movement, and when disrupted it can cause a reduction in size and speed of the movement

Question 43

Where is dopamine produced?

Answer 43

Substantia nigra - and this ability is lost w/ dopamine due to the degregation of the substantia nigra | substantia nigra cells lost

Question 44

Question 45

Knowledge check: If someone has drug induced parkinsons - symptoms can be reduced w/ the stopping of the drug * just like in delrium

Question 46

Hallmark sign of parkinsons is that movement is affected movement activation and loss of reflexive or automatic movement Movement becomes reliant on cortical control. The ability to perform known tasks, such as walking, changing direction, writing, and basic activities of daily living is diminsihed - we can't just rely on the motor cortex * Tremor * Rigidity * The kinesias * Gait * Posture

Question 47

Most common initial manifestation of parkinsons

Answer 47

Tremor

Question 48

Are tremors unilateral or bilatearl?

Answer 48

Unilateral

Question 49

Where do tremors normally start? * what do intial tremours typically loook like? * When are they most obvious, in movement or at rest? * Do you have them during sleep?

Answer 49

Start in upper limb for months or years --> can spread to all 4 limbs as well as neck and facial muscles First seen as a rhythmic, back and forth motion of the thumb and finger, referred ti as the pill rolloing tremor most obvious at rest or during stressful periods Tension or exertion will cause the tremor to increase, and it will disappear during sleep Deep brain stimulation is very effective for managing a tremor

Question 50

Rigidity is another common sign of parkinsons * Does it appear unitlaterally or bilatearlly? * Does it occur distal or proximal * Does it appear in the UE or LE first * What is one of the first signs of rigidity? * Is it velocity dependent or independent?

Answer 50

usually appears unilatearlly and proximally in the UE and then spreads to the other extremitites and trunk One of the earliest signs of rigidity is the loss of associated movements of the arms when walking - so not erciprocal arm swing / lacking arm swing when walking' Velocity independent resistance to passive stretch * So you don't have to move it quickly to trigger that rigidity

Question 51

What is lead pipe rigidity?

Answer 51

Slow and sustained resistance * like pushing on a hard peice of medal

Question 52

Cogwheel rigidity

Answer 52

Jerky response * It will have a little give then be stuck again, then have a little give etc.. * Think a clunky wheel that has some give then stops

Question 53

Bradykinesia is common w/ parkinsons what is this?

Answer 53

Slowness of movement

Question 54

Hypokinesia is common w/ parkinsons what is it?

Answer 54

decreasing range and size of movement * they can't do those larger movements * Arent picking up feet as much (not going in that full ROM) - that loss of range and size of movement * Why we do those BIG exercises

Question 55

Akinesia is common w/ parkinsons what is it?

Answer 55

Disorder of movement initaition, smallness of natural and automatic movements * difficiluty starting a movement, the first steps of walking, sit to stand

Question 55

Freezing of gait is common w/ parkinsons. What is this?

Answer 55

Sudden cessation of movement in the middle of an action sequence * often triggered by something, think walking through a door, stepping over something, turning around.

Question 56

w/ parkins can lead to/ may notice * Eye movements affected - common w/ CNS disorders * Mask-like face - not a lot of expression * Garbled speech pattern * Loss of fine motor skills * Difficulty w/ dual tasking

Question 57

Knowledge check: Which term describes a disorder of movement initiation?

Answer 57

Akinesia

Question 58

Parkinsons Gait: * highly sterotyped and characterized by impoverished movement, with distrintive features of stooped psoture, narrow-based, short shuffling steps, foot drgas or catches, Reduces arm swing, difficuty intiaiting walking or turning and slowness **Gait speed can increase at first w/ parkinsons and decrease later w/ rigidity** Festiantion = cant stop the movement

Question 59

Parkinsons posture: * Characterized by flexion of the neck, trunk, hips, and knees, with elbows bent and arms adducted * Postural instability * MSK constrains * weakness/fatigue

Question 60

Parkinsons non motor symptoms orthostatic hypotensions very common Depression = due to chemical imbalance as well as loss of function

Question 61

80% of people who have had parkinsons 20+ years progresses to dementia

Question 62

Hoehn and Yahr Classification of distability for parkinsons stage 1

Answer 62

Minimal or absent; **unilatearl** if present - tremor

Question 63

Hoehn and Yahr Classification of distability for parkinsons stage 2

Answer 63

Minimal **bilateral** or midline involvement; balance not impaired

Question 64

Hoehn and Yahr Classification of distability for parkinsons stage 3

Answer 64

**Impaired righting reflexes**: unsteadiness when turning or rising from chair; some activities restricted but patient can live **independently** and continues some forms of employment

Question 65

Hoehn and Yahr Classification of distability for parkinsons stage 4

Answer 65

All symptoms present and severe; **standing and walking possible only with assistance**

Question 66

Hoehn and Yahr Classification of distability for parkinsons Stage 5

Answer 66

Confined to bed or wheelchair

Question 67

Hoehn and Yahr Classification of distability for parkinsons

Question 68

**Knowledge check: typical gait of a parkinsons pt would look like what?** * reduced arm swing

Question 69

Diagnosis of parkinsons are based on a triad symptoms. What are they? are CT/MRI used for MRI? - what do they use if not?

Answer 69

1) Tremor 2) Rigidity 3) Akinesia CT/MRI are not helpful * Used a DATSCAN

Question 70

What is a DaTSCAN used for in parkinsons? * **for class motor symptoms of PD to be present what % of these neurons must be lost?** * however, what is the only way to be 100% sure the person has PD?

Answer 70

Use of a DaTSCAN for detecting images of the level of dopamine transporters in the brains of people w/ suspected parkinsonian syndromes * so it lets you see the lvl of dopamine Most helpful in differentaiting between PD and essential tremor, drug-induced parkinsonism, and psychogenic parkinsonism. It is not able to differentiate between PD, progressive supranuclear palsy, multiple systems atrophy, and other neurodegenerative diseases affecting the dopamine neurons in the brain. * so it cant differenet between other diseases that cause dopamine disorders (because its just detecting the existing dopamine transmitters) 50% of neurons must be lost. DaTSCAN is able to detect this decreased activity early in the course of PD, when the diagnosis may still be uncertain However, only an autopsy can conclusively determine whether a persons brain exhibits a PD pathology

Question 71

Question 72

NOTE: Parkinsons is not a death sentence. People can live full long life **Older onset = more rapid rate of progression** * along with rigid small movements being their first symptom * being male * having other things going on (stroke) we do have medications for this but it just slows it down, it continues progressing either way

Question 73

ICF body structure and function: * Kinesias fall under this * tremor, decreased flexibility Activity (gait, transfers, bed mobility) Participation (ability to work and interact socially, self-care, recreational sports, quality of life) Environmental factors (home community settings) and personal factors (resources, personal attiudes, self-efficacy, emotions and feelings) all need to be considered

Question 74

knowledge check: Rigidity in PD falls under what peice of the ICF model * Body structures/function however, if rigidity is affecting walking than that changes to actvitity

Question 75

Similar conditions to parkinsons: Dementia w/ Lewy bodies: Dementia: cognitive impairments (attention, executive function, visuospastial skills) At least one of the following: * Parkinsonian syndrome onset after or at most 12 months before onset of dementia * Fluctuations in alertness and attention - this makes it hard to work w/ * Repeated visual hallucinations

Question 76

In multisystems atrophy know that you have to have parkinsonian syndrome or cerebellar syndrome this stuff looks like parkinsons

Question 77

Progressive Supranuclear Palsy: * stiffening of the body * Lots of occular things going * overhwleming stiffness * huge loss of balance in the backwards direction

Question 78

Secondary Parkinson Syndrome * due to toxicity or a vascular issue, drug induced * Remember, if s/s arent adding up, than it might not be the normal parkinsons, something else is going on **Often this can go away**

Question 79

Question 80

Knowledge check: which of these s/s would lead you to believe that the pt is experiecing something that is not normal PD * symetric onset (its normally unilatearl at the start)

Question 81

Primary drug used to treat PD

Answer 81

Levodopa

Question 82

Side effects of dopamine agonists

Answer 82

1) nausa / vomiting 2) orthostatic hypotension 3) Confusion 4) Hallucinations

Question 83

drugs for parkinsons notice w/ anticholenrgics a lot more cardio stuff Amatadine = depression / cogntivie stuff There is no clear consensus of which drugs should be used intiatlly but most commonly is levodopa

Question 84

Adverse effects of Levodopa Therapy: * GI * Cardiovascular * Dyskinesias * Cognitive

Answer 84

GI * Nausaea / vomiting Cardiovasular * Arrythmias * OH Dyskinesias * Choreoathetoid movements * Ballismus * Dystonia * Myoclonus * Various tics and tremours Cognitive * Behavioral changes If these side effects get really bad just switch medications (theres several of them)

Question 85

Dinishied response and/or flucations in response to levodopa can happen What is end of dose akinesia? On/off phenomenon What is a drug holiday? * how long is it>

Answer 85

End of dose akinesia = when the drugs effectiveness seems to wear off prior to the next dose On/Off phenomenom: effectiveness of levodopa may suddently and spontenaouly decreasem resulting in the abrupt worsening of parkinsian symptoms - in an off period. Remission of symptoms may then occur spotaneously of after taking a dose of leadopa (the on period) * we really dont want there to be a distinct off period, we want their symptoms to be controlled - we might need to play around w/ timing / dosage

Question 86

DBS = deep brain stimulation

Question 87

Knowledge check: When are symptoms worse, the on or off period? * Off period - meaning were seeing breakthrough symptoms

Question 88

ICF