What is Huntington's Disease? - Chapter 22

What does Huntington's disease look like?

Huntington's disease is a rare hereditary brain disease with progressive motor, cognitive and neuropsychiatric impairments. The symptoms become noticeable between the ages of 30 and 50, and the duration of the disease is on average 15-20 years, until the death of the patient. The disease cannot be prevented, cured or delayed. Relief of the symptoms is possible.

How does Huntington's disease develop?

Huntington's disease is caused by a genetic mutation. The mutation consists of an excess (≥40) of repeats of the three bases C, A, and G on chromosome 4. As a child of a Huntington's patient, you have a 50% chance of developing the disease. A DNA test can be used to determine whether someone is a mutation carrier. The more CAG repeats, the sooner the disease will manifest itself. The diagnosis is based on familial predisposition, motor disorders and the DNA outcome. In the pre-manifest phase (we will come back to this later) there is a supporting DNA result and there are (subtle) cognitive and / or neuropsychiatric disorders, but no motor disorders. Such a patient is called a 'premanifest mutation carrier'.

What does Huntington look like neuropathologically? 

The gene abnormality changes the function of the huntington protein, causing cells to die mainly in certain parts of the basal ganglia (in particular the striatum: the caudate nucleus and the putamen). At an early stage and even years before the clinical manifestation there are already functional and structural brain changes: there are fewer dopamine receptors in the striatum, an altered glucose metabolism and a smaller volume of the basal ganglia. There is general atrophy at an advanced stage. Through connections with almost the entire brain, this leads to motor, cognitive, emotional and behavioral symptoms. Ultimately, areas such as the cerebral cortex, hippocampus, hypothalamus, thalamus and cerebellum are also damaged.

What does the clinical picture look like?

Motor disorders

There are mainly dyskinesias (movement disorders) characterized by chorea (more involuntary movements) and hypokinesia (fewer spontaneous movements). Bradykinesia (slowness), dystonia (disturbed muscle tension), rigidity (stiffness) and balance problems are also common. The disorders interfere with daily functioning.

Cognitive disorders

Initially there is often a bradyphrenia (slowness of information processing), but as the disease advances, more cortical cognitive impairments may occur:

• Intelligence: only affected in an advanced stage. Earlier deterioration in non-verbal performance than on verbal task. 

• Memory: memory disorders may occur at an early stage of the disorder. Encoding and retrieval of new information are impaired. recognition and general factual knowledge are spared for a longer period of time. The problems can be secondary to impairments in attention or executive problems.

• Speed ​​of information processing: the psychomotor delay is present at an early stage.

• Attention and executive functioning: problems within these domains are already present at an early stage. In addition to loss of initiative and problems with planning, there is also less self-control (recognizing and correcting errors) and self-inhibition (inhibiting behaviour). The reduced cognitive flexibility is often only indicated by family members. The problems with focusing and distributing attention are becoming increasingly prominent.

• Disease awareness: patients have no awareness of their disease (deny their symptoms) possibly due to disorders within the executive domain, a psychological protection mechanism or a physiological cause.

• Perception and spatial cognition: these are often secondary to executive problems; patients cannot group and match different forms.

• Speech and language: at an early stage there are often speech disorders such as dysarthria. As the disease progresses, speech deteriorates sharply. The language remains relatively spared although some (non-progressive) word-finding problems and problems in the grammar will arise.

• Social cognition and emotion: it seems that patients already have trouble recognizing negative emotions and understanding someone else's perspective at an early stage. However, much more research is needed into empathy, ToM and other social-cognitive functioning.

Neuropsychiatric disorders

The most common neuropsychiatric changes can also be categorized:

1. Affective disorders: the most common affective disorder is depression. This can be primary (due to a biological disorder) or secondary (in response to the disease process).

2. Apathy: especially in the advanced stage there is apathy, which results in a loss of interest, motivation and initiative.

3. Irritability: this is one of the first symptoms. This symptom is challenging to deal with, especially for family members and friends.

4. Disinhibition: the inhibition of behavior can manifest itself in all areas, such as eating, drinking, sexuality or talking.

5. Compulsiveness.

6. Psychotic symptoms.

Physical problems

Weight loss is the most obvious physical problem, probably partly caused by motor problems in chewing and swallowing.

How is Huntington's disease diagnosed?

Thee pre-manifest stage

The precise onset of the disease cannot really be determined. For example, there may already be 'minor motor abnormalities' in the pre-manifest stage, as well as subtle changes in cognitive functioning such as a slowed pace and executive problems.

The diagnostic process

On the basis of the UHDRS scale, the neurologist can determine the severity of cognitive symptoms for different domains. The PBA is used for neuropsychiatric complaints. During a neuropsychological assessment the cognitive symptoms are objectively mapped. Due to the lack of insight into the disease, it is important that someone closely related to the patient is clinically interviewed. Then, within the multidisciplinary team (consisting of a neurologist, psychiatrist, physiotherapist, occupational therapist, speech therapist and activities therapist), appropriate treatment is chosen that can be aimed at the patient and / or the environment. Often this treatment plan also includes psycho-education, behavioral therapy and cognitive rehabilitation.