Huntington Disease and Other Choreas

Huntington disease (HD) has traditionally been considered a movement disorder, but cognitive and psychiatric symptoms also prominently factor into its clinical presentation. Depression is one of the most common psychiatric disturbances in HD, with its prevalence highest in manifest disease during stage 2, but it is also present during the illness prodrome (the period before manifestation of motor symptoms). Identification and treatment of depression in individuals with the HD mutation is an essential part of clinical management in this population, especially owing to the high risk of suicide. This article summarizes what is currently known about the presentation and treatment of depression in the early stages of HD and provides advice to clinicians treating this population. Huntington disease: beyond motor symptoms Huntington disease (HD) is a neurodegenerative disorder caused by an increased number of DNA trinucleotide repeats in the Huntingtin (HTT) gene on chromosome 4 [1,2]. When the number of cytosine–adenine–guanine (CAG) repeats on at least one copy of this locus is increased to more than 35, an individual will develop HD. It is a dominant mutation; therefore, the chances of offspring inheriting the mutation are 50%. Affected individuals develop gradual destruction of neurons in the striatum and cortex, leading to the motor symptoms of chorea, rigidity and bradykinesia, with degeneration over 20 years leading to death. The length of the CAG repeat is inversely correlated with the age of onset of motor symptoms, which on average occurs between the ages of 35–45 years. No treatments are available to prevent or reverse neurodegeneration in HD. The diagnosis of HD is traditionally based on the presence of motor symptoms; however, the cognitive and behavioral symptoms constitute a significant aspect of HD morbidity, affecting the ability to work, manage finances and perform other daily activities [3]. Early mortality may also occur due to increased risk of suicide. Cognitive deficits affect memory, visuospatial abilities and executive function, often resulting in dementia.

A triplet repeat (CAG) expansion mutation in the huntingtin gene on chromosome 4 is responsible for Huntington's disease (HD). Presymptomatic genetic testing for this mutation has identified clinically normal persons who are virtually certain to develop this dementing illness if they live a normal lifespan. The present study sought to determine whether these "mutation-positive" persons have impairments in cognitive functioning. Seventy-five mutation-positive persons did not differ from 128 mutation-negative persons on tests selected for their sensitivity to early-stage HD. Interestingly, however, those with the mutation viewed themselves as more likely to develop HD than did those without the mutation. Among mutation-positive subjects, having a longer CAG repeat mutation was likewise not associated with cognitive impairment. However, being closer to estimated disease onset (a product of repeat length and parent's age at onset) was associated with selected cognitive impairments. When viewed in light of previous studies showing atrophy of the caudate nucleus and putamen in mutation-carriers who are close to onset but not those far from onset, these results suggest that subtle changes in brain and behavior may be detected shortly before subjects with the HD mutation develop sufficient signs and symptoms for diagnosis. Conceptual and methodological problems associated with the search for presymptomatic cognitive and behavioral indicators of dementing illness are discussed. (JINS, 2002, 8, 918-924.)

The Journal of Clinical Psychiatry, 2008

Movement Disorders, 2016

Tremor and other hyperkinetic movements (New York, N.Y.), 2014

The objective of this study was to identify important attributes associated with the triad of symptoms (cognition, emotional-behavioral, and motor) of Huntington's disease (HD) from patient, caregiver, and medical provider perspectives to facilitate development of a new disease-specific, health-related quality of life (HRQOL) instrument. We conducted a targeted literature review of HD and HRQOL instruments, expert surveys, and patient and caregiver phone-based interviews to extract information on the symptoms and issues most relevant to the HD symptom triad (HD triad). The data collected from these sources were used to generate themes and subdomains and to develop an integrated schema that highlights the key dimensions of the triad. THE SEARCH IDENTIFIED THE FOLLOWING AREAS: emotional functioning/behavioral changes (e.g., positive emotions, sadness/depression); cognitive functioning (e.g., memory/learning, attention/comprehension); physical functioning (e.g., motor functioning, ...

Journal of Nervous & Mental Disease, 2004

Neurodegenerative Disease Management, 2011

SUMMARY Huntington disease (HD) has traditionally been considered a movement disorder, but cognitive and psychiatric symptoms also prominently factor into its clinical presentation. Depression is one of the most common psychiatric disturbances in HD, with its prevalence highest in manifest disease during stage 2, but it is also present during the illness prodrome (the period before manifestation of motor symptoms). Identification and treatment of depression in individuals with the HD mutation is an essential part of clinical management in this population, especially owing to the high risk of suicide. This article summarizes what is currently known about the presentation and treatment of depression in the early stages of HD and provides advice to clinicians treating this population.

Journal of Psychiatric Research, 2002

Individuals at-risk for Huntington disease (HD), both HD gene carriers and nongene carriers, were recruited to determine whether psychological changes are detectable among clinically presymptomatic individuals who carry the HD allele. Each participant underwent genotyping to determine HD gene carrier status and a clinical assessment that included a quantified neurological examination and an abbreviated Minnesota Multiphasic Personality Inventory (MMPI): the Hypochondriasis, Depression, Psychasthenia, Neuroticism, Cynical Hostility, and Irritability Scales and the Harris Subscales of Depression. The results of the MMPI were evaluated for differences between nongene carriers (NGC) (n=363), presymptomatic gene carriers (PSGC) (n=149), and those with manifest HD (MHD) (n=26). The overall multiple analysis of variance was not significant, indicating that there was no overall difference among the three groups. However, when subscales of the MMPI were examined individually, participants with manifest HD scored higher on the Psychasthenia scale (MHD vs. PSGC, P=0.005; MHD vs. NGC, P=0.03) and the Harris Depression subscale, Brooding (MHD vs. PSGC, P=0.0005; MHD vs. NGC, P=0.003). No significant correlation was found between the number of trinucleotide repeats on the disease-producing allele and any of the MMPI scales for the gene carriers, MHD or PSGC. These results verify the presence of psychological symptoms in the early phases of MHD but not in PSGC. Thus, further study of the behavioral and mood symptoms thought to accompany HD using measures designed specifically to detect depressive symptoms and changes in behavior specific to HD is warranted to delineate the timing of onset of the psychological symptoms.

Archives of Neurology, 2000

Background: In juvenile Huntington disease (HD), dystonia as well as parkinsonism and eye movement abnormalities may be the predominant motor signs rather than chorea. Several patients have come to our attention with adult-onset HD in whom there is prominent dystonia and minimal chorea (ie, an adult-onset form of HD that resembles juvenile HD). Objectives: To estimate the prevalence of these cases of dystonia-predominant HD in a clinic and to study the relationship between the motor phenotype and age of onset in HD. Methods: The Unified Huntington's Disease Rating Scale (UHDRS) was administered to 127 subjects during their initial visit to the Huntington's Disease Center at the New York State Psychiatric Institute, where dystonia, chorea, bradykinesia, rigidity, and eye movements were rated. The dystonia score was the mean UHDRS rating of dystonia in 5 body regions; the chorea score, the mean rating of chorea in 7 regions; the bradykinesia score, the mean rating of axial and limb bradykinesia; the rigidity score, the mean rating of rigidity in both arms; and the eye movement score, the mean rating of ocular pursuit, saccade initiation, and velocity. Dystonia-predominant HD was defined by the severity of dystonia relative to the severity of chorea. Results: Fifteen (11.8%) of 127 subjects had dystoniapredominant HD. Age of onset correlated negatively (r=−0.22, P=.02) with the dystonia score divided by the chorea score and negatively (r=−0.28, P =.002) with the severity of dystonia, bradykinesia, and eye movement abnormalities relative to chorea (ie, [(dystonia score + bradykinesia score + eye movement score)/3] − chorea score), suggesting that subjects with younger ages of onset had more severe dystonia, bradykinesia, and eye movement abnormalities relative to chorea. Conclusions: Cases of adult-onset HD with prominent dystonia and a paucity of chorea may represent 1 in 8 cases in specialty clinics. Age of onset was clearly associated with the motor phenotype. A younger age of onset was associated with more severe dystonia, bradykinesia, and eye movement abnormalities relative to chorea, supporting the notion that in adult-onset HD, the motor phenotype forms a continuum with respect to age of onset.

2008