Lecture 12: Motor 2: Huntington: Chapter 22 Flashcards
What is the prevalence of huntington disease? Are there differences in western vs. non-western countries? What could be an explanation?
0,6-13,7 individuals per 100.000 in western
Only 1-7 individuals per 1.000.000 in non-western
Apparently it’s related to the European genetics
What does it mean that huntington is autosomal dominant inherited?
This means if 1 parent has huntington, you will have 50% chance of inheriting it and developing huntington
What is huntington’s disease?
A hereditary neurodegenerative brain disease that is characterized by progressive motor impairments, cognitive decline and mood/behavior changes
When is the typical onset of Huntington’s? And what is the duration?
Between 30-50
Duration: 15-20 years
How does Huntington disease look in the DNA?
Repeated sequences of CAG
- More than 36 repeats indicates huntington’s
- The number of repeats indicates severity/course
How can Huntington’s disease start?
When your parents don’t have it, but you have an unlucky 27-35 repeats of CAG, you can be the first in your family
What is a premanifest mutation carrier?
An individual that carries the gene, but motor impairments are absent. Often cognitive impairments are there and later motor impairments will come
What is huntingtin? What is its function?
The protein that is made by the gene involved in Huntington’s.
Function: nervous system development and cell adhesion
What is toxic gain-of-function disease?
If a mutation occurs, the proteins gain a new function and does something it didn’t do before
What happens in translation of genes in Huntington disease?
Proteins clump together, which make it hard to read DNA in the cell. So it interrupts communication
Where does the first and most severe neurodegeneration occur in the brain? What is the function of this area?
In striatum (caudate nucleus and putamen)
Function: coordinating movements
Degeneration in which brain areas explain motor issues, cognition issues and psychiatric symptoms in Huntington’s?
Motor: striatum
Cognition: loss of neurons/thinning in cortex and white matter
Psychiatric: dopaminergic system
What is the consequence of striatal degeneration? (3)
- Involuntary movements
- Tremors
- Poor coordination
What age is the median onset of motor issues in HD?
Age 45 (change from prodromal into clinical phase)
What are some prodromal issues in HD?
Lower functionability, some cognitive impairment. Motor functions intact
Why do people with HD die from the disease?
Motor complications, such as not being able to swallow anymore
What are 3 motor symptoms in HD?
- Involuntary movements
- No rhythmic or repetitive movements/almost dance-like
- Difficulty walking
What are 4 key cognitive symptoms of HD?
- Attention
- Mental flexibility
- Planning
- Emotion regulation
Late stages of HD are similar to…
Alzheimer’s disease
What were the results of the TRACK-HD study aimed on identifying the earliest detectable changes in HD?
Early cognitive deterioration, especially in cognitive tests that had a motor or psychomotor component (such as stroop word-reading test)
What percentage of HD patients suffer from depression and how can you explain this?
50% –> difficult to live with such a disease
What is the frontal lobe syndrome in HD?
Disinhibited, inappropriate behavior in the predromal stage
What 2 psychiatric features are common in late stage HD?
Irritability and apathy (passivity)
What is a good predictor of long-term care in HD?
Motor and cognitive features (not psychiatric)
What are 5 typical concerns in the quality of life of people with HD?
- Emotional issues
- Social issues
- Physical issues
- Cognitive issues
- End-of-life issues
What is the relation between the defective gene and huntingtin protein?
The gene defect alters the function of the protein, leading to toxic gain-of-function disease
What are some brain changes in the premature stage of HD? (2)
- Fewer dopamine receptors in striatum
- Smaller basal ganglia volume
What is chorea?
Involuntary movements
What is hypokinesia?
Less spontaneous movements
What is bradyphrenia?
Slowness of information processing
How is intelligence affected in HD?
Often unaffected until late stages of the disease. Earlier deterioration in non-verbal performance than verbal tasks
How is memory affected in HD?
Affected in early stage, especially in areas of encoding and retrieving new information. Recognition and general knowledge are spared a bit longer
How is speed of information processing affected in HD?
Affected in early-stage
How is executive functioning affected in HD?
Regulation of cognition and behavior is impaired in early stages. Self-control and inhibition, planning and initiating activity is difficult. They have cognitive inflexibility and can’t deal well with unexpected events
How is attention affected in HD?
Early stage start difficulties dividing attention
How is the disease awareness in HD? Give 3 explanations
Patients hardly complain about their movements or cognition.
- Lack of insight in disease and consequences
- Denial is cause of psychological defense mechanisms
- Patient may have no subjective experience of their motor impairments
What are perceptual and spatial cognition issues in HD? Explain
Difficulty in distinguishing and matching shapes –> possibly due to executive impairments
What are language and speech problems in HD?
Word finding and grammar remains intact in earlier stages.
Decrease in loudness of speech (hypophonia) and articulation (due to motor issues)
What is hypophonia and what is dysarthria?
Hypophonia: speaking softer and softer
Dysarthria: difficulty in articulation
How is emotional and social cognition impacted by HD?
Difficulty recognising negative emotions and understanding emotions in others from another perspective. However, more research is needed
What are psychotic symptoms in HD and how often do they occur?
Delusions and hallucinations
Occur less often than other neuropsychiatric symptoms
What is the unified huntington’s disease rating scale (UHDRS)?
This scale indicates the severity of the disease in the domains of motor control, cognition, mood, behavior and daily functioning
What is psychological preparedness?
The idea that you know what to expect when starting treatment
Why is it important to do a heteroanamnesis in Huntington’s?
Because the patients themselves often have little awareness of the disease
What is a drug used in HD and what is its effect?
Tetrabenazine –> manages chorea (involuntary movements) in HD
When are antipsychotics and antidepressants used in HD?
Antipsychotic: treat involuntary movements
Antidepressant: treat anxiety or depression
What are 4 types of interventions for HD? What is the aim of each?
- Physical therapy
–> Maintain mobility and reduce rigidity - Occupational therapy
–> Improve/adapt daily living - Speech and language therapy
–> Improve communication - Palliative care
–> Improve quality of life, ensure dignity
What are gene silencing strategies (GSS)?
Emerging approach in treatment of HD. It disables messengers, so the defective gene never translates in a huntingtin protein
What does a multimodal prediction of onset mean?
Include multiple sources of evidence (neuroimaging, family history) to reach an accurate prediction
What happens in research that aims at identifying disease modifiers?
Looking for the thing that makes the disease slower
Why is it important to understand comorbidities of HD and things like diabetes/heart disease?
Important to see what the respective roles of genetics vs. lifestyle are
Why are global registries for HD research important?
The disease is very rare, so it’s hard to get enough participants. We have to bundle information internationally
What is an important limitation of current HD treatments?
No cures yet, just therapies that aim at symptom management
What is the main focus of current HD research? (3)
- Gene silencing strategies (GSS)
- Identify disease modifiers
- Improve quality of life for patients
