Huntington's Disease

Front 1

Definition of Huntington's Disease

Back 1

A dominant genetic disease that manifests in early to middle adulthood and causes up to 40 years of slow neurodegenerative decline before it eventually kills.

Front 2

Cardinal symptoms of Huntington's

Back 2

Motor disturbance (chorea)
Cognitive impairment
Psychiatric features

Front 3

What is HD diagnosis based on?

Back 3

Neurological evaluation
Requires the presence of an unequivocal movement disorder that cannot be explained by other causes

Front 4

What is the genetic trinucleotide that repeats abnormally in HD? What is the typical number of repeats and how many times does it repeat in HD?

Back 4

CAG (cytosine, adenosine, guanine), encodes protein huntingtin
Typically 10-30 repeats
Over 39 repeats in HD

Front 5

What is the relationship between repeat length and age of onset of HD?

Back 5

Inverse relationships, more repeats = earlier onset; length of the CAG repeat explains about 50-60% of the variance in age of onset

Front 6

For a child of a parent with HD, what is the chance of inheriting the disease?

Back 6

50%

Front 7

What is confirmatory testing?

Back 7

Confirm diagnosis of HD in a person with symptoms of HD with or without family history

Front 8

What is predictive testing?

Back 8

Inform a healthy individual who wants to know whether (s)he carries the expanded gene

Front 9

What is prenatal testing?

Back 9

Determine the risk status of a fetus

Front 10

What are the adverse effects of receiving genetic test results?

Back 10

Impact on family members, relationships, employment, and insurance; psychosocial risks (i.e. mental health)

Front 11

Describe brain atrophy in HD

Back 11

Diffuse

Front 12

Where is neuronal loss / gliosis the worst?

Back 12

Caudate nucleus and putamen

Front 13

What is the location of the earliest neuropathological changes associated with HD?

Back 13

Medial paraventricular portion of the caudate nucleus, the tail of the caudate, and to a lesser extenet in the dorsal putamen

Front 14

In what directions does neurodegeneration typically progress?

Back 14

laterally and basally

Front 15

On neuroimaging, where do subtle structural and functional brain changes begin before onset of symptoms? How long before symptom onset do those changes occur?

Back 15

Striatum: atrophy, reduced glucose metabolism, reduced dopamine receptor binding, and neuron loss; nuclear inclusions
Occur a decade before symptom onset

Front 16

What is the general function of the indirect and direct pathways of the basal ganglia?

Back 16

The indirect pathway inhibits the flow of information
The direct pathway facilitates the flow of information

Front 17

In HD, what changes occur in the indirect motor circuit and what problems does this cause?

Back 17

Selective loss of neurons in the putamen reduces inhibitory signals from the GPI/SNr to the ventral thalamus.
Thalamus projects excessive excitatory signals to the precentral motor strip
Leads to chorea

Front 18

In HD, what changes occur in the direct motor circuit and what problems does this cause?

Back 18

Loss of neurons containing “substance P” occurs, removes inhibitory signal to the GPi/ SNr?
Decreased discharge of excitatory signal to the premotor cortex
Leads to rigid akinesia, reduction in the amount of movement exhibited by patient

Front 19

Disruption of the dorsolateral circuit is associated with what symptoms?

Back 19

Executive dysfunction and motor programming abnormalities. Poor organization skills, memory retrieval deficits, poor set shifting

Front 20

Disruption of the orbitofrontal circuit is associated with what symptoms?

Back 20

Increased irritability, impulsivity, mood lability, tactlessness, and socially inappropriate behavior; mood and/or obsessive compulsive disorder

Front 21

Disruption of the anterior cingulate circuit is associated with what symptoms?

Back 21

Decreased motivation, apathy, decreased speech, akinesia

Front 22

Typical early signs of HD include what forms of motor disorder?

Back 22

interrupted pursuit of gaze, inability to suppress reflexive glances to novel stimuli, hypometric saccades, tongue impersistence, impaired rapid alternating movements, and akathisia

Front 23

What motor problems are observed in the later stages of HD?

Back 23

Choking is an increasing hazard due to problems coordinating chewing, swallowing, and breathing. May become immobile and bedridden.

Front 24

What aspect of cognitive function does not deteriorate until advanced stages?

Back 24

memory

Front 25

Age of onset of juvenile-onset HD

Back 25

before 21

Front 26

prevalence of juvenile-onset HD

Back 26

3.5-6% of cases

Front 27

What symptoms are common between adult-onset and juvenile-onset HD?

Back 27

Triad (motor, cognitive, psychiatric)

Front 28

What aspects of presentation are more often observed in juvenile onset?

Back 28

Distinctive motor profile: extrapyramidal rigidity, dysarthria (?)

SEIZURES

Front 29

Is HD cognitive impairment a good example of a cortical or subcortical syndrome?

Back 29

subcortical

Front 30

What features of Alzheimer’s dementia are usually lacking in HD?

Back 30

Aphasia, amnesia, agnosia

Front 31

With regard to the stages of learning and memory, which one is thought to be relatively preserved in HD and which is impaired?

Back 31

Memory storage preserved
Impaired encoding, retrieval, and working memory

Front 32

Prevalence of depression

Back 32

9-63%

Front 33

How common is depression compared to other psychiatric symptoms for people with HD?

Back 33

Most common symptom in beginning and middle stages. May diminish in later stages (second most common in stages 4 and 5), but still highly prevalent.

Front 34

What is the prevalence of suicidal ideation in HD?

Back 34

10%; two critical periods.
1. Frequency of ideation jumps to 19.8% when soft neurological signs develop
2. Jumps from 17% to 21.6% from stage 1 to 2

Front 35

How common is suicide in HD compared to the prevalence in other neurological disorders?

Back 35

Suicide more common than in other neurological disorders

Front 36

How common is suicide in HD compared to the prevalence in the general population?

Back 36

4 to 6 times higher, one study found 8 to 20 times higher

Front 37

Prevalence of psychosis in HD

Back 37

3-12%

Front 38

Is psychosis more common in early-adult onset or in middle to late adulthood onset HD?

Back 38

More common among early-adult-onset cases

Front 39

Compared to psychosis in schizophrenia, is psychosis in HD more or less resistant to treatment?

Back 39

More resistant

Front 40

Prevalence of OCD in HD

Back 40

OCD not truly prevalent in HD
Prevalence of obsessive and compulsive behaviors is 13-30%

Front 41

What is the nature of obsessive thoughts in HD?

Back 41

Perseveration, get stuck on a previous occurrence or need and are unable to shift

Front 42

What is the association of aggressive outbursts and admission to a psychiatric facility?

Back 42

Aggressive outbursts are often the principal reason for admission to a psychiatric facility

Front 43

How do aggressive outbursts affect residential placement for treatment?

Back 43

Difficulty with placement due to aggression was among the principal obstacles to providing effective continuum of care

Front 44

How does agitation rank among behaviors that interfere with caring for a person with HD?

Back 44

Agitation is the most prominent behavior problem cited

Front 45

What is the relationship of apathy and depression in HD?

Back 45

Apathy is common (59%) in HD and is separable from depression (70%); not correlated, r = -0.15, p = .40

Front 46

What is the relationship of apathy and lower cognitive function?

Back 46

Apathy correlated with cognitive function

Front 47

What is the prevalence of apathy in HD?

Back 47

59%? More common than temper outbursts

Front 48

Lack of awareness of illness in HD is due to...

Back 48

neurological pathology, NOT psychological defenses

Front 49

What is anosognosia?

Back 49

term that describes lack of awareness of pathology due to neuropathology

Front 50

What is the relationship of severity of awareness deficits and cognitive impairment?

Back 50

Performance on WCST and visual-spatial subtests of the WAIS-R correlated with anososngosia

Front 51

Is there a curative treatment for HD? What treatments are available?

Back 51

No
behavioral interventions

Front 52

What is symptomatic treatment?

Back 52

Symptom reduction and maximizing functional capacity

Front 53

How often do HD patients present with complaints of abnormal movements? Who usually requests that patients receive treatment for chorea?

Back 53

Rarely
Family members or professionals

Front 54

How does treatment of chorea impact frequency of falling or intelligibility of speech?

Back 54

Pharm. management of chorea will not decrease falling or improve intelligibility of speech; assistive devices helpful.

Front 55

What medication has been shown to indirectly inhibit the release or synthesis of glutamate, an excitatory neurotransmitter?

Back 55

Gabapentin and riluzole