Huntington's Disease Flashcards
Definition of HD
Huntington’s disease (HD) is a progressive, hereditary neurodegenerative disorder that primarily affects movement, cognition, and psychiatric function. It is caused by an autosomal dominant mutation in the HTT gene on chromosome 4, leading to an abnormal expansion of CAG trinucleotide repeats. This results in the production of a toxic form of huntingtin protein, which leads to neuronal degeneration.
Area of Nervous System Affected in HD
HD primarily affects the basal ganglia, particularly the caudate nucleus and putamen. These structures are critical for motor control, cognitive function, and behavior.
Early stage: Degeneration of the striatum (caudate nucleus and putamen) → choreiform movements
Later stages: Widespread brain atrophy, including the cortex, leading to dementia and severe motor impairment
Epidemiology (Incidence/Prevalence) of HD
Prevalence: 5-8 per 100,000 individuals worldwide
Higher incidence in European populations, lower in Asian and African populations
Each child of an affected parent has a 50% chance of inheriting the disease
Cause of HD
HD is caused by a mutation in the HTT gene on chromosome 4, which results in an expanded CAG trinucleotide repeat: Autosomal dominant trinucleotide repeat disorder
Normal range: ≤ 26 repeats
Intermediate range: 27-35 (no symptoms but may pass to offspring)
HD range: ≥ 36 repeats
Juvenile HD: > 60 repeats (earlier onset and more severe progression)
Genetic involvement in HD
Autosomal dominant inheritance
Each child of an affected parent has a 50% chance of inheriting the HD gene
If a child does not inherit the gene, they will not develop or pass on the disease
If the HD gene is inherited, the disease will develop at some point
Inheritance is independent for each child
Course of HD
HD progresses in three general stages:
- Early Stage:
Mild involuntary movements (chorea)
Subtle cognitive changes (difficulty with multitasking, executive function)
Mood disturbances (irritability, depression) - Middle Stage:
Increased chorea
Speech and swallowing difficulties
Impaired voluntary movements
Cognitive and psychiatric decline - Late Stage:
Severe motor impairment (rigidity, bradykinesia)
Loss of independent function
Inability to speak or swallow
Death often due to aspiration pneumonia or complications of immobility
Prognosis of HD
Average survival: 15-20 years post-diagnosis
Some patients survive 30-40 years
No cure, but symptom management can improve quality of life
Hallmark signs and symptoms in HD
- Motor Symptoms: Chorea, dystonia, bradykinesia, impaired coordination
- Cognitive Symptoms: Executive dysfunction, memory deficits, judgment impairment
- Psychiatric Symptoms: Depression, anxiety, aggression, psychosis, suicidal ideation
Motor versus sensory involvement in HD
Motor: Prominent (chorea, dystonia, rigidity, dysarthria, dysphagia)
Sensory: Largely spared (no significant sensory loss)
Subtypes of HD
Adult-Onset HD (Most Common)
Onset: 30-55 years
Symptoms: Chorea, cognitive decline, psychiatric symptoms
Juvenile HD (Westphal Variant)
Onset: Before age 21
Symptoms: Rigidity (instead of chorea), bradykinesia, seizures, rapid progression
Diagnostic tests
Genetic Testing: Confirms presence of CAG repeat expansion
MRI/CT Scans: Shows caudate nucleus atrophy
Neurological Examination: Assesses movement, cognition, and behavio
Medication for HD
- Chorea Management:
Tetrabenazine, Deutetrabenazine (VMAT2 inhibitors)
Atypical antipsychotics (e.g., Olanzapine, Risperidone) - Psychiatric Management:
SSRIs (Fluoxetine, Sertraline) for depression
Mood stabilizers (Valproate, Lamotrigine) for aggression - Cognitive Symptoms: No effective treatment
Treatment for HD
Multidisciplinary Approach:
Neurology, psychiatry, speech-language therapy, physiotherapy, occupational therapy
Physical Therapy: Maintains mobility and prevents falls
Speech-Language Therapy (SLT): Manages communication and swallowing difficulties
Nutritional Support: Prevents weight loss and malnutrition
Rating scale/outcome measure for HD
Unified Huntington’s Disease Rating Scale (UHDRS)
Motor function
Cognitive function
Behavioral symptoms
Functional capacity
Cognition in HD
- Executive dysfunction (early stage)
- Memory impairment (later stages)
- Judgment and decision-making difficulties
Characterized initially by a
loss of speed and flexibility.
This may be seen first in complex tasks, when the patient is unable to keep up
with the pace and lacks the flexibility required to alternate between tasks.
Cognitive losses accumulate and patients develop more global impairments in the later stages of the disease.
Judgement
Memory
Concentration
Language in HD
- Speech difficulties due to dysarthria
- Problems with word retrieval, syntax, and discourse organization
- Reduced spontaneous speech
- Increased difficulty understanding complex discourse and drawing inferences
- Latency of response
- WFDs
- Decreased length of utterance, use of syntactical complexities
- Topic maintenance
SLT assessment for HD
Motor Speech Examination (assessing dysarthria)
Language Assessment (word retrieval, syntax, discourse)
Swallowing Evaluation (Videofluoroscopy, FEES)
SLT Intervention for HD
Speech Strategies: Slow speech rate, breath control, prosody drills, speaking on exhalation, rhythmic breathing, Yes/No system
Educate conversational partner
Alternative Communication: Alphabet boards, speech-generating devices, Etran frame
Swallowing Therapy: Postural adjustments, texture modifications, PEG feeding in late stage
Dysarthria in HD
Hyperkinetic:
Reflects underlying movement disorder
Involuntary contractions of muscle
groups which cant be predicted by speaker
Can involve all subsystems of speech
Interference with articulation
Episodes of hypernasality
Harshness
Breathiness
Unplanned variation in loudness
Altered rate
Prolonged phonemes and intervals between words
Stress equalised
Inappropriate silences
Specific to HD:
Sudden forced inspiration/expiration
Articulatory breakdowns
Phonatory impairment (harsh,strained-strangled
quality, excessive loudness)
Prosody impairment (monopitch, monoloudness,
reduced stress, short phrases)
Features of dysphagia in HD
Hyperkinetic subgroup:
rapid lingual chorea
swallow incoordination
repetitive swallows
prolonged laryngeal elevation
inability to stop respiration
frequent eructations.
Rigid-bradykinetic subgroup:
mandibular rigidity
slow lingual chorea
coughing on foods
choking on liquids.
Saliva management in HD
Saliva Management
Excessive Drooling (Sialorrhea):
Botulinum toxin injections
Anticholinergic medications (e.g., Glycopyrrolate, Scopolamine patches)
Thickened Fluids: Helps reduce aspiration risk
Associations/charities for HD
- Huntington’s Disease Association (HDA)
- Huntington’s Disease Society of America (HDSA)
- European Huntington’s Disease Network (EHDN)
- International Huntington Association (IHA)
History of HD
In 1872, American physician George Huntington wrote about an illness he
called “an heirloom from generations away back in the dim past.”
One of its earliest names was chorea, the Greek word for dance, which
describes how people affected with the disorder writhe, twist, and turn in
a constant, uncontrollable dance-like motion.
