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| MRI. Source: Radiopaedia |
Definition:
Huntington’s disease (HD) is a progressive neurodegenerative autosomal dominant disease characterized by disturbed movements, changes in behaviour, and cognitive decline. Although the motor disturbances are both choreatic and hypokinetic, chorea is the most characterizing.
Choreatic movements are irregular, unwanted involving not only the limbs and the trunk but also the respiratory and buccolingual muscles. HD is caused by a CAG repeat expansion of the HTT gene on the short arm of chromosome 4. The mutant protein huntingtin causes neurodegeneration in the brain, particularly in the caudate nucleus and putamen. The mean age at onset is in the third and fourth decade of life and the disease duration about 15-20 years. Death usually results from respiratory complications. Studies to the cause of death in HD found that the primary cause of death is pneumonia.
Source: Aspiration pneumonia and death in Huntington’s disease. Anne-Wil Heemskerk; Raymund A.C. Roos LUMC Leiden netherlands
Juvenile Huntington's disease:
Adult HD is characterised by a triad of clinical features including: chorea, cognitive decline and psychiatric disturbance or behavioural disturbance . However, in JHD, particularly in those with onset in the first decade, chorea is less likely to be present and instead, patients are more likely to present with rigidity, bradykinesia, dystonia and gait disorder, ie. parkinsonian features. In addition, JHD patients are more likely to develop epilepsy than adult-onset cases. The spectrum of features at presentation can also include ataxia, dysarthria, dysphagia, deterioration in school performance or severe behavioural problems
Source: Current Pharmacological Management in Juvenile Huntington’s Disease. Lisa Robertson and al. Sheffield Children's Hospital UK
Irritability:
Irritability is a frequently reported neuropsychiatric disorder in HD, in addition to depression, anxiety, apathy, and obsessive-compulsive behaviors. HD irritability has been defined as a temporary psychologic state characterized by impatience, intolerance, and reduced control over temper, which can progress to angry and aggressive verbal or behavioral outbursts. Estimates of irritability vary from 31% to 65% according to studies using different methods of sampling and measurement. A study comparing self and care-partner assessment shows a higher reported incidence for irritability when information is obtained from care-partners, suggesting a component of lack of awareness in patients. However, many are aware and recognize that they are too easily provoked, and take more time to calm down after provocation. Irritability can precede the onset of motor symptoms of HD and it occurs over all stages of disease. However, measures of irritability do not track with disease progression. Further, patients differ in the degree to which they experience irritability: some “feel” irritable, some exhibit mild irritability without further behavioral manifestations, while the behavior of others can escalate to physical aggression. At all levels of severity, it is vital to recognize irritability as part of the disease process, and not to mischaracterize patients as difficult, stubborn, or “character disordered” which adds to strain experienced by patients and families. Early recognition and treatment of this symptom is important because irritability behaviors that escalate can be a tipping point in terms of care partner burnout and subsequent need to institutionalize HD patients.
Source: An International Survey-based Algorithm for the Pharmacologic Treatment of Irritability in Huntington’s Disease. Mark Groves and al. Departments Beth Israel Medical Center, New York
Cognitive decline:
HD was traditionally thought to be mainly a movement disorder at least in the early stages and a clinical diagnosis was based solely upon the motor features of the disease. It is now widely accepted that cognitive and psychiatric disturbances are almost universal, begin early in the course of the disease, are heterogeneous and contribute substantially to the functional disability of those affected. Anecdotal evidence from families and caregivers along with recent findings suggest that it is the cognitive and psychiatric profile of HD that contributes most to the patient’s quality of life and behavioural functioning, and not their motor phenotype. This is particularly apparent in the pre-symptomatic stages where the first noticeable impairment in functioning is often reported as a loss of ability to continue to work at their highest occupational level.
Source: "Cognitive follow up of a small cohort of Huntington’s disease patients over a 5 year period".Sarah L. Mason et al. University of Cambridge UK. PLos currents
Sleep and circadian abnormalities:
Deficits in sleep and circadian function have been observed in HD patients and in HD mouse models . As expected, deficits in sleep-wake patterns have profound consequences in many physiological functions. In HD patients, abnormal sleep patterns correlate with symptom severity, specifically in depression and cognitive dysfunction, and in caudate atrophy. HD patients have abnormal sleep patterns, with increased sleep onset latency, frequent awakening, and changes in the normal EEG pattern.
Source: "Circadian Abnormalities in Motor Activity in a BAC Transgenic Mouse Model of Huntington’s Disease". Stephen Oakeshott et al. PsychoGenics Inc. PLos currents. 2012-03-26