Huntington's Disease: A Clinical Review

Therapeutic Advances in Neurological Disorders, 2013

The management of patients with chorea, in particular Huntington’s disease, is a complex task requiring skills in a number of areas. This paper reviews new knowledge on this topic and places it in the context of established procedures. It is focused on Huntington’s disease, since this is the disorder, for which most publications on management have been published in the past few years. Management starts with appropriate diagnosis and differential diagnosis, with the aim of finding disorders with chorea amenable to causative treatment. The place of genetic testing and the importance of genetic counselling is stressed, as well as the importance of precise observation in the course of the disorder to tailor appropriate therapies. Pharmacological treatment is based on poor evidence but to a large extent on expertise from centres devoted to the care of patients with Huntington’s disease. It is focused mainly on motor and psychiatric aspects of the phenotype. Nonpharmacological treatment i...

Neurologic Clinics, 2009

Huntington's disease is a genetic neurodegenerative condition transmitted by means of autosomal dominant inheritance. It causes irreversible neuronal damage and leads to disintegration of motor and cognitive functions within two decades after onset. There is no known cure for the disease; however, research is being carried out on prevention of its reproduction in the next generations. The disease has detrimental effects on the health and wellbeing, both mental and physical, of the patient, and causes great emotional and psychological pressure on their friends and family.

Frontiers in Neurology, 2019

Given that any symptoms of Huntington's disease (HD) may be worsened by stress, fatigue and intercurrent disorders (e.g. anxiety, digestive disorders, infectious or painful conditions, etc.), these aspects must be assessed and should be treated with appropriate measures in parallel with treating the Huntington's symptoms (Professional agreement). Motor disorders The wide spectrum of motor manifestations are the best known and the most visible symptom in Huntington's disease. Among them, involuntary movements (i.e. chorea) are the most obvious. However, while the diagnosis of manifest HD is based on the presence of motor symptoms, these are frequently preceded by cognitive and behavioral symptoms (1). While motor symptoms are easily detected, and might be the source of anxiety and ostracism, they are often well tolerated by the patients and their proxies in contrast to cognitive and behavioral symptoms that often lead to family and social/professional's issues. Chorea Chorea is characterized by abnormal, involuntary, spontaneous, uncontrollable, irregular, intermittent, non-rhythmic and aimless movements affecting the trunk, the face and the limbs. They are worsened by fatigue and challenges such as emotional stress, and usually disappear during sleep. Affecting about 90% of the patients, chorea is a key element of establishing the clinical diagnosis, but is not always a marker of the severity of the disease (2). Chorea may be absent at the beginning of HD or appear transiently during the course of the disease, and is rarely present with juvenile onset. After motor onset, chorea usually progresses towards a peak phase and then commonly decreases in severity in the later stages of HD, at which time it may disappear alongside an increase in rigidity and/or dystonia (3). Recommendations 1. Drug treatment should be considered if chorea causes the patient distress or discomfort (Professional agreement). 2. Tetrabenazine was shown to have a beneficial effect on chorea (Grade A) (4-20) and is one of the first-line treatments for this symptom. 3. Tetrabenazine has to be used with caution due to the potential of adverse events, which should be explained to patients and relatives/caregivers (Professional agreement). 4. Tetrabenazine is contraindicated when the patient suffers from not well-managed depression or suicidal thoughts, as specified in the product monographs. 5. Tiapride (21-27), sulpiride (28-33) (Grade B), olanzapine (34-43), risperidone (28,44-49), pimozide (9,24,50,51) and aripiprazole (52-57) (Grade C) showed efficacy on chorea and are first-line treatments for this symptom in particular when the patients have associated personality and/or behavioural or psychotic disorders. 6. Haloperidol has a national marketing authorization for chorea in some countries (Grade C) (58-63). It should be considered as second-line treatment but should be used with caution due to the risk of major apathy (Professional agreement). 7. Because of contradictory results in various trials, amantadine cannot be recommended to treat chorea (Grade B) (63-67). However, despite the poor tolerability (confusion and legs oedema) of amantadine several experts of the multidisciplinary group, consulted to evaluate the recommendations, reported a beneficial effect of amantadine to treat chorea. 8. On a regular basis, ongoing treatments should be re-evaluated for their efficacy and tolerability. If effective and well-tolerated, changing ongoing treatment is not recommended (Professional agreement). 9. It may be necessary to reduce the dose or change a neuroleptic or tetrabenazine if the patient experiences adverse events such as worsening of apathy or extrapyramidal side effects (Professional agreement). 10. Monotherapy to treat chorea is preferred because combination therapy (e.g. tetrabenazine and neuroleptic) increases the risk of adverse effects and may complicate the management of non-motor symptoms. Adjunct therapy should therefore be considered on a case-by-case basis for patients who do not respond significantly to monotherapy (Professional agreement). 11. Riluzole (Grade A) (39,68-71) and memantine (Grade C) (44,72-74) are not indicated for the management of chorea. 12. Globus pallidus Deep Brain Stimulation (DBS) (either internal or external) is not yet recommended in severe pharmacoresistant chorea (Grade C) (75-86). The technic is currently assessed in therapeutic trials. 13. In the presence of disturbing chorea, appropriate protective measures (for meal time, washing, bedding, transfers...) should be put in place in order to avoid traumatic injury or chokes. Rehabilitation specialists such as occupational therapists, psychomotor therapists, speech therapists, physiotherapists can help identify appropriate assistive technology devices and positioning techniques (Professional agreement). 14. Where there are recurrent oral-lingual injuries due to biting, mouth guards (splints) may be prescribed, in collaboration with a dentist/oral health specialist where possible. The choking risk due to mouth guards should also be considered (Professional agreement). 15. As an adjuvant measure, therapies that might act by relaxing the patient (e.g. aquatherapy or bathing) might be of benefit to improve transitorily chorea symptoms (Professional agreement). Dystonia Dystonia is highly prevalent in HD patients (90%) and is characterized by abnormal postures that may affect all body segments and is frequently associated with rigidity (54-59)(87). When dystonia manifests in HD, the intensity varies from a slight intermittent abnormal posture, without any impact on independence, to severe twitch of muscles with major impact on movements and functions of daily living. It can lead to impaired chewing and swallowing (for dystonia of the face and the neck), joint deformities, and compromise a comfortable sitting position and prevent secure ambulation (especially when severe axial dystonia is present). Recommendations 1. Both active rehabilitation, with patient participation, and passive rehabilitation, without voluntary participation of patients, in physiotherapy are recommended as a preventive measure in order to maintain the range of joint motion, limit postural and musculoskeletal deformities and, prevent the development of contractures (Professional agreement). 2. The injection of botulinum toxin in the case of focal dystonia (e.g. cervical dystonia, blepharospasm, oromandibular dystonia) or to prevent secondary deformities (e.g. flexum, equinus) should be performed by a trained professional (Professional agreement). 3. The concomitant use of anticholinergic agents to prevent the side effects of neuroleptics has not demonstrated efficacy and should not be used (Professional agreement). 4. The use of adapted equipment, in particular customised chairs, can provide an optimised and comfortable environment in view of the dystonia-related deformities (Professional agreement). Rigidity Rigidity is an increase in muscle tone leading to a resistance to passive movement that can induce joint stiffness and limited range of motion. In HD, it might be related to spasticity and/or parkinsonism (with bradykinesia). Bradykinesia is the slowness of initiation of voluntary movement with a reduction of speed and amplitude, particularly of repetitive actions. Akinesia is a severe degree of bradykinesia leading to inability to initiate voluntary movement. In HD, bradykinesia frequently coexists with involuntary choreatic movements. At late stages, when choreatic activity declines, most HD patients develop an akinetic-rigid syndrome often with a generalized increased tone. Juvenile or late-onset patients often exhibit a predominantly bradykinetic phenotype with or without rigidity but little to no chorea (88). This phenotype might be misdiagnosed as atypical parkinsonism or a psychiatric condition. Recommendations Only low levels of scientific evidence have been provided for the treatments of rigidity and because of the risk of adverse events, they should be used with caution. Nevertheless, rigidity symptoms might be distressing for patients and the following treatments might be attempted on a case by case basis (Professional agreement). 1. Rigidity may be increased or induced by the use of neuroleptics or tetrabenazine. If this impacts the functional capacity of the patient, a reduction in dosage or the withdrawal of neuroleptics and/or tetrabenazine should be considered taking into account overall benefit on chorea and/or behavioural symptoms vs. severity of rigidity (Professional agreement).

Journal of Huntington's disease, 2020

Background: Anosognosia, or unawareness of illness of deficits, has been observed in Huntington's disease (HD) in relation to motor and cognitive signs and symptoms. Most studies of awareness in HD have used self-report questionnaire methodology rather than asking patients to report on their symptoms in real-time. The two studies in which patients were asked about their chorea in real-time had small sample sizes and only examined patients early in disease progression. Objective: To examine awareness of chorea in real-time in HD patients across a broad range of disease progression. Methods: Fifty HD patients across motor and cognitive impairment severity were asked if they noticed any involuntary movements after completing a simple working memory task used to elicit chorea. A movement disorders specialist rated the presence or absence of chorea while the patients completed the task. Disagreement between the patient and movement disorders specialist's ratings was considered to be an indicator of unawareness. Results: Approximately 46% of patients who exhibited chorea did not report chorea. Eighty-eight percent of participants who acknowledged chorea did not report chorea in all parts of the body that chorea was observed. Conclusions: HD patients demonstrate unawareness of chorea across cognitive and motor sign severity.

The Consultant Pharmacist, 2009

HD is an inheritable, fatal, neurodegenerative condition that is associated with disorders of movement, cognition, and behavior. Initially regarded as a "true" autosomaldominant disorder (i.e., no appreciable difference in disease expression between homozygotes and heterozygotes), recent studies reveal that homozygotes present with a more severe clinical course. The responsible gene located at chromosome 4p16.3 encodes the Objective: Review Huntington's disease (HD) and the role of tetrabenazine (TBZ) in treating chorea associated with this disease. Discuss the pharmacology, side-effect profile, drug interactions, precautions, and contraindications of TBZ. Data Sources: Literature identified within MEDLINE and PubMED. Study Selection: Two manuscripts specifically regarding the management of chorea in patients with HD were identified. Additionally, studies involving the clinical use of TBZ were reviewed. Data Synthesis: The literature identified provided information regarding the efficacy, safety, and pharmacological actions of TBZ. Conclusion: HD is often accompanied by chorea, and the treatment with TBZ in this patient population often results in decreased chorea. Pharmacists managing patients on TBZ need to be well versed in TBZ's potential side effects, drug interactions, and unique dosing considerations.

Purpose of review There are many causes for chorea, including genetic, autoimmune, pharmacological, and structural lesions. Where appropriate, treatment is based on reversing the underlying cause of chorea; many cases are self-limited, resolving when the primary disorder is treated. This review focuses on the management of chorea due to untreatable causes. Recent findings There are a limited number of double-blind randomized control trials assessing the efficacy of specific chorea treatments. Most therapeutic recommendations are based on small open-label studies, case reports, and expert opinion. This is in part due to the heterogeneity of chorea and chorea-associated syndromes and the variety of neurodegenerative phenotypes with variable progression rates. Summary Chorea can be treated with a variety of medications ranging from antiepileptics to antipsychotics. The recent development of selective vesicular monoamine transporter blocking agents has allowed for targeted chorea management with minimal side effects. Neurosurgical interventions such as deep brain surgery (DBS) and pallidotomy are reserved for medication-refractory chorea. As a symptom of neurodegenerative disease, chorea is only one aspect of the basal ganglia syndromes, and often, a multidisciplinary approach tailored to individual patient needs provides the best management.

The Lancet, 2007

Search strategy and selection criteria I searched Pub Med from 1965-2005 for the term "Huntington's Disease" cross referenced with the terms "apoptosis", "axonal transport", "mitochondria", "animal model", "proteosome", "transcription", "juvenile", "suicide", "neurotransmitters", "age of onset", "identical twins", "neurodegeneration", and "imaging". I translated all non-English language publications that resulted from this search strategy. I mainly selected articles from the past fi ve years, but did not exclude commonly referenced and highly regarded older publications. I also searched the reference lists of articles identifi ed by this search strategy and selected those that I judged relevant. Several review articles and book chapters were included because they provide comprehensive overviews beyond the scope of this Seminar. The reference list was further modifi ed during the peer-review process based on comments from the reviewers. Year Event Publications (n)* 1374 Epidemic dancing mania described .. 1500 Paracelsus suggests CNS origin for chorea .. 1686 Thomas Sydenham describes post-infectious chorea .. 1832 John Elliotson identifi es inherited form of chorea 1 .. 1872 George Huntington characterises Huntington's disease 5 ..