CONCISE GUIDANCE TO GOOD PRACTICE A series of evidence-based guidelines for clinical management Long-term neurological conditions:management at the interface betweenneurology, rehabilitation and palliative care NATIONAL GUIDELINES British Society of Rehabilitation Medicine Clinical Standards Department Guideline Development Group The purpose of the Clinical Standards
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A Physician's Guide to theManagement ofHuntington Disease Second Edition Adam Rosenblatt, M.D.
Neal G. Ranen, M.D.
Martha A. Nance, M.D.
Jane S. Paulsen, Ph.D.
Reprinted in Canada with generous funding from the Trillium Foundation andthe kind permission of the authors, Foundation for the Care and Cure ofHuntington's Disease, and Huntington's Disease Society of America A Physician's Guide to theManagement ofHuntington Disease Second Edition Adam Rosenblatt, M.D.
Martha A. Nance, M.D.
Assistant Professor of Psychiatry Park Nicollet Clinic Clinical Director St. Louis Park, MN Baltimore Huntington's Disease Center Director, HD Clinic, Hennepin The Johns Hopkins University School County Medical Center, of Medicine Minneapolis, MNClinical Assistant Professor Neal G. Ranen, M.D.
of Neurology Medical Director University of Minnesota School of Medicine Health Pathways of Albright Care Services, York, PA Jane S. Paulsen, Ph.D.
Clinical Associate Professor of Psychiatry Associate Professor of Psychiatry Pennsylvania State College of Medicine and NeurologyDirector, Huntington's Disease Clinic and Research ProgramUniversity of Iowa School of Medicine published byHuntington Society of Canada, 1999 The indications and dosages of drugs in this book have either been recommended in the medical litera-ture or conform to the practices of physicians expert in the care of people with Huntington disease. Themedications do not necessarily have specific approval from the Food and Drug Administration for theindications and dosages for which they are recommended. The package insert for each drug should beconsulted for uses and dosage approved by the FDA. Because standards for dosage change, it is advis-able to keep abreast of revised recommendations, particularly those concerning new drugs.
Statements and opinions expressed in this book are not necessarily those of the Huntington's Disease Society of America, Inc., nor does HDSA promote, endorse, or recommend any treatment ortherapy mentioned herein. The lay reader should consult a physician or other appropriate health careprofessional concerning any advice, treatment or therapy set forth in this book.
1999 Huntington's Disease Society of AmericaAll rights reserved.
It has been five years since the publication of A Physician's Guide to the Management of Huntington'sDisease, by Drs. Ranen, Peyser, and Folstein. A great deal has changed, not only in the field of HD re-search, but also in the many clinical disciplines which can be brought to bear in the treatment of thiscondition. Some things, regrettably, have changed little. Huntington disease remains a daunting problemfor patients and families, and for physicians. A doctor caring for patients in a community setting may haveseen only one or two previous cases. The information found in this guide may help foster a sense of hope.
Huntington disease is a well-studied condition and, although there have been few systematic trials of the interventions we will suggest, this book is the product of many years of both research andhands-on experience. We have organized this edition, like its predecessor, around the three generalmanifestations of Huntington disease: motor abnormalities; cognitive changes; and various psychiatricdisturbances. We provide several generally accepted pharmacological and non-pharmacological treatmentsfor each problem. In addition, the national lay organizations, such as the Huntington's Disease Society ofAmerica (HDSA) and the Huntington Society of Canada (HSC), and their local branches, are alsoexcellent sources of information and assistance for patients, family members, caregivers, physicians, andother health care professionals (see Appendix 1).
Major changes from the first edition include the addition of a section on the genetics of HD and the use of both confirmatory and presymptomatic testing; a reworking of the section on psychiatric disor-ders to reflect major changes in the available medications over the last several years; and, the expansion ofthe cognitive section to include more recommendations about coping skills and management of behav-ioural problems.
There are many incurable diseases, such as diabetes mellitus, emphysema, or HD. It is important to remember that incurable does not mean untreatable, that even untreatable diseases may have treatableconsequences, and that patients and their families can still benefit greatly from an accurate diagnosis,prognosis, education and support. It is our hope that, with the aid of this guide, a physician meetingsomeone with Huntington disease will not say "You've got HD.There's nothing you can do about it," butinstead will be able to say, "You've got HD, and I can help." Table of Contents OVERVIEW AND PRINCIPLES OF TREATMENT Principles of Treatment Genetic Counselling Basic Genetics – Inheritance Pattern The Huntingtin (IT-15) Gene and the Huntingtin Protein CAG Repeats in the Huntingtin Gene CAG Repeat Number and Age of Onset Instability of the CAG Repeat Number Absent Family History of HD Prenatal Testing THE MOVEMENT DISORDER Rigidity, Spasticity, and Dystonia Myoclonus, Tics, and Epilepsy Swallowing Difficulties General Safety Measures THE COGNITIVE DISORDER Lack of Initiation Irritability and Temper Outbursts Perceptual Problems Impaired Initiation of Speech Disorganization of Language Content Learning and Memory The Progression of Cognitive Impairments THE PSYCHIATRIC DISORDER Specific Psychiatric Diagnoses Pharmacotherapy of Depression Psychiatric Symptoms not Belonging to a Specific Diagnostic Category Sexual Disorders End of Life Issues Voluntary Agencies Brain Tissue Bank Predictive Testing Clinics Rehabilitative/Adaptive Equipment and Product Information Sample Rehabilitation Survey Sample Disability Letter REFERENCES AND ADDITIONAL READING Overview andPrinciples of Treatment Huntington disease is a hereditary neurodegenerative disorder caused by an expansion in the IT-15, orhuntingtin, gene on chromosome 4, which encodes the protein huntingtin. HD is inherited in autosomaldominant fashion, so that each child of an affected parent has a 50% chance of developing the disease. Mostpeople with HD develop the symptoms in their forties and fifties, although there may be subtle changes muchearlier. About 10% of patients have onset of symptoms before age 20 (juvenile HD) and 10% have onset afterage 60.
Huntington disease manifests as a triad of motor, cognitive, and psychiatric symptoms which begin insidiously and progress over many years, until the death of the individual. The average survival time afterdiagnosis is about fifteen to twenty years, but somepatients have lived thirty or forty years with the disease.
Survival of HD Patients over Time
The movement disorder is characterized both by the emergence of involuntary movements, or chorea,and by impairment of voluntary movements. This latterimpairment often contributes more to disability than thechorea itself, resulting in reduced manual dexterity,slurred speech, swallowing difficulties, problems withbalance, and falls. Both chorea and impairment ofvoluntary movements progress in the middle stages ofHD, but later, chorea often declines as patients become rigid and unable to initiate voluntary movements.
Patients in this advanced state are unable to care forthemselves.
The cognitive disorder is characterized initially Duration of Illness 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 toalternate between tasks. Cognitive losses accumulate and patients develop more global impairments in thelater stages of the disease.
The most common specific psychiatric disorder in HD is depression. Patients may also suffer from mania or obsessive compulsive disorder. Other symptoms (which may not fit a specific psychiatric category)include irritability, anxiety, agitation, impulsivity, apathy, social withdrawal and obsessiveness.
HD can be roughly divided into three stages. Early in the disease, patients are largely functional and may continue to work, drive, and live independently. Symptoms may include minor involuntary move-ments, subtle loss of coordination, difficulty thinking through complex problems, and perhaps a depressedor irritable mood. In the middle stage, patients will probably not be able to work or drive and may no longerbe able to manage their own finances or perform their own household chores, but will be able to eat, dress,and attend to personal hygiene with assistance. Chorea may be prominent, and patients will have increasingdifficulty with voluntary motor tasks. There may be problems with swallowing, balance, falls, and weightloss. Problem solving becomes more difficult because patients cannot sequence, organize, or prioritizeinformation.
In the advanced stage of HD, patients will require assistance in all activities of daily living. Al- though they are often nonverbal and bedridden in the end stages, it is important to note that patients seemto retain fair comprehension. Chorea may be severe, but more often it has been replaced by rigidity, dysto-nia, and bradykinesia. Psychiatric symptoms may occur at any point in the course of the disease, but areharder to recognize and treat late in the disease.
HD with onset in childhood has somewhat different features. Chorea is a much less prominent feature, and may be absent altogether. Initial symptoms usually include attentional deficits, behaviouraldisorders, school failure, dystonia, bradykinesia, and sometimes tremor. Seizures, rarely found in adults, mayoccur in this juvenile form. Juvenile-onset HD tends to follow a more rapid course, with survival less than15 years. The vast majority of patients with juvenile onset have inherited their HD gene from an affectedfather. The reason for this tendency is now understood in genetic terms and will be explained in detail inchapter 2.
The HD gene was identified in 1993. It contains a repeating sequence of three base-pairs, called a triplet repeat. An excess number of CAG repeats in the gene results in a protein containing an excessnumber of glutamine units. The normal function of huntingtin is not known, but the expansion of thehuntingtin gene is likely to be a so-called "gain of function" mutation. In HD, huntingtin protein encodedby the abnormal gene collects in the nucleus of the cell, giving rise to a structure called an inclusion body.
Similar intranuclear inclusions have been seen in other neurodegenerative disorders caused bypolyglutamine expansions. The mechanism by which the protein aggregation may cause a brain disorder isnot fully understood. The neurons may first become dysfunctional then undergo progressive degenerationand die. Certain neurons appear to be more vulnerable in HD. Atrophy is most marked in the corpusstriatum of the basal ganglia, including the caudate and putamen. In later phases of the disease, otherregions of the brain may be affected.
The clinical diagnosis of HD is made on the basis of the family history and the presence of an otherwise unexplained characteristic movement disorder, and is usually confirmed by a gene test. The genetest can be particularly useful when there is an unknown, or negative family history (as occurs in cases ofearly parental death, adoption, misdiagnosis, or non-paternity) or when the family history is positive, but thesymptoms are atypical. The discovery of the huntingtin gene has greatly simplified the diagnostic evaluationof an individual suspected to have HD. The implications of the diagnosis of HD for the patient and familyare profound, and provision should be made for genetic counselling of individuals affected by the results.
Genetic counselling and genetic testing are discussed more fully in chapter 2. It is important to rememberthat the gene test only determines whether or not the HD-causing genetic expansion is present, and notwhether an individual's current symptoms are caused by the HD gene.
HD remains a clinical diagnosis. The motor disorder can be delineated and followed longitudinally using a quantitative examination designed for HD, such as the Quantified Neurological Examination, or theUnified Huntington's Disease Rating Scale, which also includes a useful scale for functional capacity. TheMini-Mental State Examination is useful in following the cognitive disorder longitudinally, but it lackssensitivity in certain areas which are affected in Huntington disease and may be supplemented by a moresophisticated cognitive battery such as the Mattis Dementia Rating Scale.
PRINCIPLES OF TREATMENT Caring for patients with HD is both challenging and rewarding. At times, the lack of definitive treatmentscan be frustrating, but careful attention to the changing symptoms and good communication betweenprofessionals, family members, and affected individuals all contribute to the successful management of thedisease.
HD is a progressive disease. The symptoms evolve over time such that treatments which were effective in the early stages may be unnecessary, or problematic later on, and vice versa. For example,medications such as neuroleptics may be started in the early to middle stages to control chorea. However,this category of medications may exacerbate the rigidity and bradykinesia of the later stages, and result indelirium or oversedation as the cognitive disorder progresses. The medication list and the rationale for eachmedication needs to be reevaluated at regular intervals. Sometimes the most helpful intervention a physi-cian can perform is to discontinue an unnecessary drug.
Symptoms vary over time as a patient passes through different stages of the disease. Symptoms also vary from individual to individual, even within a family. For example, one patient may develop a severemood disorder, requiring multiple hospitalizations, but have little motor disability. The patient's brother mayhave debilitating motor symptoms, but no mood disturbance at all. Thus interventions need to be tailoredto individual symptoms, and fearful patients should be reassured that their symptoms may not necessarilyresemble those of their relatives.
HD patients, like others with injuries to the brain, are highly vulnerable to side effects, particularly cognitive side effects, of medications. The physician should begin with low doses and advance medicines slowly. Polypharmacy should be avoided where possible. Many of the drugs used in treating symptoms ofHD, such as neuroleptics and antidepressants, will not have immediate efficacy and patients need to be toldthat they may feel worse before they feel better, because they will experience the side effects, before thebeneficial effects have appeared.
Pharmacologic interventions should not be launched in isolation, but in a setting of education, social support, and environmental management. Symptomatic treatment of HD needs to be approached likeany other medical problem. The clinician should elicit the details of the symptom, its character, onset andduration, and its context including precipitating, exacerbating and ameliorating factors. A differentialdiagnosis should be generated, non-pharmacologic interventions should be considered, and the clinicianshould have a way of determining whether the goals of treatment are being met and should formulate acontingency plan if treatment is not working. Sharing some of this reasoning process with patients andfamilies can be reassuring.
Patients with HD will often be accompanied by a caregiver on visits to the doctor. This caregiver can be a crucial informant, particularly in the later stages of the disease, when speech and cognitive difficul-ties may prevent patients from supplying a history. However, both patient and caregiver may not feel com-fortable discussing certain important issues in each other's presence, such as irritability, driving, relationshipissues, or sexual problems. Therefore an effort should be made to speak to both individuals alone during thevisit.
A few words should be said on the issue of "alternative treatments" for Huntington disease— unproven remedies such as herbs, megadose vitamins, homeopathic preparations, or magnetic devices,which are to be distinguished from experimental treatments taking place as part of a scientific study. Pa-tients should be encouraged to discuss their ideas about these therapies and not to be afraid to tell theirphysicians that they are trying them. This will allow the doctor to help the patient think through the prosand cons of such a decision, to avoid notoriously dangerous or ineffective nostrums, and to monitor for sideeffects. Patients should understand that there is no substance, no matter how "natural," which haspharmacologic activity without side effects, and that all treatments carry an element of risk.
We have found it useful to share certain caveats with patients to minimize the risk for those who have chosen to pursue these alternative therapies: 1) Don't spend too much money 2) Don't do somethingthat common sense suggests is dangerous and 3) Don't neglect or discontinue effective medical treatmentsin favour of an unproven therapy. By following these principles patients are likely to avoid harm.
Physicians wishing to locate scientific treatment trials for their patients may wish to contact one of the national voluntary agencies listed in Appendix 1. Notices about new trials also appear in newsletters ofregional and national HD organizations. An important sponsor of clinical trials is the Huntington StudyGroup, an international consortium of scientific investigators from academic and research centres who arecommitted to cooperative planning, implementation, analysis and reporting of controlled clinical trials andother therapeutic research for HD. Contact the national voluntary agencies (Appendix 1) for the most up-to-date information about participating sites.
GENETIC COUNSELLING The discovery of the gene has led to new insights about HD. Not all patients or family members will want orneed genetic testing, but all should be offered genetic counselling. This can be provided by the physician or byreferral to a genetic counsellor. Here are some of the issues that may be explained: BASIC GENETICS – INHERITANCE PATTERN HD is an autosomal dominant disease, which means it affects males and females with equal likelihood. Eachchild of an affected individual has the same 50% chance of inheriting the abnormal huntingtin gene, andtherefore developing the disease one day. Inheriting a normal huntingtin gene from the unaffected parentdoes not prevent or counteract the disease-causing effects of the abnormal gene.
THE HUNTINGTIN (IT-15) GENE AND THE HUNTINGTIN PROTEIN The huntingtin gene directs the cell to make the huntingtin protein, whose function is unknown. Huntingtinprotein contains a sequence in which the amino acid glutamine is repeated a number of times. Theseglutamine residues are encoded in the gene by the DNA trinucleotide "CAG." The number of times that"CAG" is repeated (the CAG repeat number) determines the number of consecutive glutamines in thatsegment of the huntingtin protein. The huntingtin protein is made in normal amounts, whether it has anormal or excess number of glutamines, but it appears to be processed differently when it has an excessnumber of glutamines, so that the protein accumulates in the neuron. The details of this process and how itrelates to the development of neurologic disease are currently being studied.
CAG REPEATS IN THE HUNTINGTIN GENE The normal and abnormal CAG repeat number ranges have been determined only by clinical experience,which includes that of about 10,000 affected and unaffected individuals worldwide. Normal huntingtingenes contain 10–35 "CAG repeats." Repeat sizes of 27–35 are at the upper end of the normal range, andwill not result in HD, but sometimes increase into the abnormal range in the next generation, particularly ifpassed on by a male. The risk for this event has not been quantified. 36–39 repeats are at the low end of theabnormal range, but may not result in HD in the course of a normal life span. People with 40 or morerepeats will develop HD if they live a normal life span.
CAG REPEAT NUMBER AND AGE OF ONSET There is a rough inverse correlation between the CAG repeat number and the age of onset of HD symp-toms. However, the CAG repeat number accounts for only about half of the variation in age of onset.
Therefore, although it may be possible to give an age range inwhich symptoms are most likely to occur, the age of onset Correlation of Age of Onset with
cannot be accurately predicted from CAG number alone.
Triplet Repeat Length
The CAG number also does not accurately predict whatsymptoms an individual will have, or how severe or rapid thecourse of the disease will be.
INSTABILITY OF THE CAG REPEAT NUMBER The number of CAG repeats in somatic cells does not changeduring an individual's life, and genes with normal repeat sizesare almost always transmitted stably to the next generation.
In contrast, genes with expanded CAG repeat sizes are prone to expand further as they are passed on to a child, particu-larly in the case of paternal transmission, although expan-sions can occur in maternal transmission as well. Thus, children who inherit the abnormal gene often have a larger repeat number than the affected parent, andmay consequently tend to develop symptoms at a younger age. The earlier onset of symptoms in a childthan a parent is called anticipation. In extreme cases, symptoms may be evident in the child while thefather is still asymptomatic.
ABSENT FAMILY HISTORY OF HD Some individuals develop HD without ever knowing they were at risk, because they have no known familymembers with the disease. This occurs in 2–5% of all cases. Sometimes this can be explained by early deathof a parent who carried the gene, but did not live long enough to manifest the symptoms, by adoption, or bymistaken paternity. Others represent "new mutations," caused by rare expansions of parental genes with ahigh-normal CAG repeat number (27–35 repeats) into the affected range in the child. Individuals with highnormal CAG repeat sizes are not themselves at risk for developing HD. Our understanding of the signifi-cance for their offspring is likely to improve, and they may be best referred to someone with specializedknowledge, such as a genetic counsellor.
With the discovery of the gene a simple and accurate genetic test became available. The HD gene testusually requires a blood sample, but can be performed on other tissues, such as skin, amniocytes or chori-onic villus cells, or autopsy material. The test requires special molecular diagnostic facilities, but at least twodozen university and commercial laboratories in North America perform gene tests for HD.
Genetic testing for HD is potentially useful in three clinical situations: diagnostic, or confirmatory testing; predictive, or presymptomatic testing; and prenatal testing.
Diagnostic genetic testing refers to the use of a gene test in a patient who has symptoms suggestive of HD,with or without a family history. If the clinical suspicion is strong, this may be the only diagnostic testneeded. It is important to remember that the presence of the huntingtin gene with an increased repeatnumber does not mean that a patient's current symptoms are caused by HD, as the gene is present through-out life. Particularly in children, who have the most to lose by premature genetic diagnosis, the gene testshould be used sparingly, and only when the neurologic symptoms strongly suggest the onset and progres-sion of HD.
Confirmatory testing should be performed in a patient who appears to have HD if no other affected family members have previously had a gene test, to be sure that the "family disease" is really HD and notsome other condition. Diagnostic genetic testing is also very useful in the evaluation of an individual whoappears to have HD but who has a negative or absent family history.
A special note should be made about the effects of an individual's gene test on the individual's family. The presence of an expanded HD gene in one individual has direct implications for that person's children, siblings, and perhaps his parents and collateral relatives. Any physician who diagnoses HD in apatient must be prepared to face questions from and about these additional family members. Consultationwith a genetic counsellor may help to make this difficult situation easier.
Predictive testing refers to the use of an HD gene test in a person who has no symptoms but wants to knowwhether or not he carries the expanded gene. Predictive testing of healthy individuals requires a differentclinical approach than the one to which physicians and patients are most accustomed. There are no directmedical indications for or benefits from a predictive test. There are also potential psychosocial risks topredictive testing, including adverse effects on the individual's mood, on relationships with friends andfamily and on insurability and employability. Predictive testing should be reserved for competent adults whohave participated in a careful discussion of their genetic risks and the potential risks and benefits of the testitself.
The World Federation of Neurology, the International Huntington Association, and the Huntington's Disease Society of America have published guidelines regarding the genetic and psychologi-cal counselling and support that should surround predictive testing. In Natural reproduction without genetic keeping with these guidelines, Huntington disease predictive testing centres have been established in various provinces. Referral of interested Prenatal testing by amniocentesis or patients to a predictive test centre is highly recommended. A referral list chorionic villus sampling of facilities offering predictive genetic testing for Huntington disease may Non-disclosing prenatal test be found in Appendix 2.
Decision not to reproduce (may include sterilization) Artificial insemination RENATAL TESTING Surrogate mother Pre-implantation genetic testing and Prenatal testing for HD is possible, and should be performed in conjunc- tion with detailed genetic counselling. Affected or at-risk individuals orcouples should be informed of all of their reproductive options (shown inTable 1), with the understanding that different options are appropriate or desirable for different people. For those who desire prenatal testing, the best time to make arrangements isprior to the pregnancy. Chorionic villus sampling can be performed very early, at 8–10 weeks, and a non-disclosing prenatal test, which determines only whether the fetus received a chromosome from the affectedgrandparent or the unaffected grandparent, without determining whether the fetus or at-risk parent actuallycarries the HD gene, requires samples from several individuals.
There are two parts to the movement disorder associated with Huntington disease: the presence of involun-tary movements, and the impairment of voluntary movements. The involuntary movements are called chorea,or choreoathetosis, and consist of irregular jerking or writhing movements. Chorea is the most noticeablefeature of HD. In fact, the condition is often referred to as Huntington's chorea, yet the impairment of voluntary movement is more highly Principles Of Treatment Of
correlated with functional disability. Abnormal eye movements (inter- The Movement Disorder
rupted pursuit and slow, hypometric saccades), slow and uncoordinatedfine movements, dysarthria, gait disturbance, and dysphagia can be Consider non-drug interventions first.
largely independent of chorea and may limit a person's ability to work, Pharmacologic treatment of chorea may care for himself, and communicate. Although it is tempting to treat the worsen other aspects of the movement highly noticeable chorea of Huntington disease right away, it is impor- disorder, cognition, or mood.
tant to remember that the drugs used to suppress chorea can have Chorea may diminish over time, reducing the disadvantages of their own, including worsening of voluntary motor need for treatment.
Many patients are not bothered by their chorea and may not even be aware of most of the movements. Thephysician and patient first need to establish whether the chorea requires any treatment at all. Is the choreasevere enough to interfere with voluntary activities such as writing, cooking, or eating? Does severe choreaseem to be causing falls or accidents? Is highly visible chorea a significant source of distress for the patient? Before beginning medication for chorea, non-pharmacologic interventions should be considered.
Chorea, like most forms of involuntary movement, is worsened by stress, anxiety, or depression, is decreased during sleep, and often varies with posture or positioning. Treatment of underlying mood and anxietydisorders, and providing a calm, predictable environment are a first step. Various assistive devices may behelpful. These include padded, reclining chairs, padding for the bed, and wrist and ankle weights to reducethe amplitude of the chorea. Sources for some of these devices are provided in Appendix 3.
Doctor and patient also need to have realistic expectations for pharmacotherapy. Medications will not alter the progression of the underlying illness. They will not improve speech or the ability to swallow,prevent falls, or improve fine motor control. In fact, drug-related side effects such as sedation and rigiditymay increase the risk of falls and decrease the intelligibility of speech. However, reduction of severe choreamay improve gross motor control and may be of cosmetic value.
Akathisia is an extremely uncomfortable internal sense of restlessness, sometimes induced by neuroleptics, which may cause patients to pace, or be unable to sit still. It can be mistaken for agitation oranxiety, prompting the physician to increase the dose of the offending drug, creating a vicious cycle.
The movement disorder of HD changes over time. In most patients chorea eventually peaks and then begins to decline, while rigidity and bradykinesia become more significant. At this point, the drugs thathelped to suppress chorea may no longer be needed, and in fact may worsen HD-related rigidity. Thereforeit is important to assess the need for anti-chorea medication at regular intervals, and perhaps to makeperiodic trials of dose reduction or discontinuation.
Medications Used To Suppress Chorea
sedation, parkisonism, dystonia, akathisia, dry mouth, weight gain less parkinsonism less parkinsonism, more sedation and postural similar to thiothixene sedation, ataxia, apathy, withdrawal seizures hypotension, sedation, Three classes of medication are commonly used to suppress chorea in Huntington disease: neuroleptics, such as haloperidol and fluphenazine; benzodiazepines, such as clonazepam and diazepam; anddopamine depleting agents, such as reserpine and tetrabenazine. Each class has its advantages and disad-vantages.
The suppression of movement, regarded as a side effect when neuroleptics are used to treat psycho- sis, is the desired effect when they are used to treat chorea. Therefore the most popular neuroleptic agentsare the high potency drugs, which can also induce the most parkinsonism. Haloperidol and fluphenazine aremost commonly prescribed. They should be started at a low dose, 0.5 to 1mg once or twice a day, andgradually increased to efficacy. Doses higher than 6–8mg per day have not generally been found helpful intreating chorea. Risperidone is a newer neuroleptic which does not cause as much parkinsonism as theother high potency agents, but is still useful in suppressing chorea and may relieve agitation as well. It maybe also be started at 0.5–1mg once or twice a day, with some patients tolerating doses as high as 6–8mgdaily.
In some cases, patients who experience unacceptable rigidity, akathisia, or dystonia with high potency agents may benefit from a lower potency neuroleptic such as thiothixene or thioridazine. This maybe preferable to adding an anticholinergic agent to the original drug to counteract the side effects. Lowerpotency agents tend to be more sedating, however, and are more inherently anticholinergic, producing moretachycardia, postural hypotension, constipation, and delirium. Thiothixene can be started at 1–2mg once ortwice a day and increased to 10–20mg/day. Thioridazine, which is even lower potency, can be started at10mg once or twice a day and increased to about 100mg/day.
Patients starting neuroleptics should be warned about two unlikely, but potentially serious adverse effects. The first is tardive dyskinesia, a syndrome of involuntary movements often first noted in the faceand mouth, that develops in some patients taking neuroleptics. Tardive dyskinesia is of concern because thesymptoms are usually permanent, and will likely be hard to recognize in someone with HD. The otherserious problem is neuroleptic malignant syndrome, a rare, but life threatening reaction characterized byacute onset of delirium, rigidity, and fever, often accompanied by leukocytocis, and elevated CPK. Familiesshould know about this so that the patient can be given prompt medical attention if it develops.
Benzodiazepines, such as clonazepam and diazepam can also be useful in the treatment of chorea.
Some clinicians prefer them to neuroleptics because they do not induce parkinsonism or tardive dyskinesia.
Sedation and the increased risk of delirium are the main deleterious side effects, along with tolerance,withdrawal symptoms, and the potential for abuse. Long acting varieties such as clonazepam and diazepamare favoured because they require less frequent dosing, provide more even coverage of symptoms through-out the day, and are less likely to precipitate withdrawal symptoms if a dose is missed. Clonazepam may bestarted at 0.5mg per day, and may be raised as high as 4mg per day, in divided doses. Diazepam may bedosed from about 1.25mg to 20mg per day, also in divided doses.
Some clinicians favour dopamine depleting agents as a treatment for chorea. While these drugs do share some of the "neuroleptic" side effects, they may be milder at low doses, and they have not been shownto cause tardive dyskinesia. The class includes reserpine and tetrabenazine. Reserpine was used in the pastas an antihypertensive, and may cause hypotension. This can be minimized by giving the drug at bedtime.
Parkinsonism, restlessness, dizziness, and sedation are other common side effects. The increased rate ofdepression in patients taking these agents is also of concern. Reserpine may be started at 0.1mg per day andincreased weekly to a dose as great as 3mg per day. Tetrabenazine is similar in action to reserpine, but is feltby some clinicians to be more effective and is less likely to cause hypotension. It can be started at 12.5mgbid or tid and increased over several weeks to a maximum of 75 or 100mg per day in divided doses.
RIGIDITY, SPASTICITY, AND DYSTONIA Rigidity and spasticity tend to emerge later in the course of Huntington disease, except in cases of child-hood onset, in which they are often present from the beginning. They can impair gait, lead to falls, andnecessitate the use of a wheelchair. Dystonia may include twisting, tilting or turning of the neck (torticollis),involuntary arching of the back (opisthotonos) and arching of the feet. It may be a symptom of HD, or aside effect of neuroleptic therapy.
A variety of medications have been used to treat rigidity, spasticity, and dystonia, all with modest success at best. Benzodiazepines, such as clonazepam, or baclofen, starting at 10mg/day and increasing up to60mg may relieve stiffness, but may also increase bradykinesia. Tizanidine, a clonidine like drug, is some-times helpful for spasticity, beginning with 2mg qhs and increasing every 4–7 days to a maximum of 12–24mg in divided doses. Antiparkinsonian medicines such as amantadine 50–200mg/day, levodopa/carbidopa25/100mg two to three times per day, or bromocriptine beginning at 1.25mg bid, increasing every fewweeks, may be helpful with bradykinesia or rigidity, and some clinicians have tried trihexyphenidyl, 2–5mg,bid to tid. All of these medicines may cause delirium and may lose their efficacy after several months.
Consultation with a physiotherapist or physiatrist to design a program to mobilize the patient and preventcontractures may be an important component to the management of rigidity and spasticity. Botulinum toxininjections have been used rarely, but might be beneficial if severe rigidity of a small muscle or group ofmuscles is disturbing function.
MYOCLONUS, TICS, AND EPILEPSY Myoclonus, sudden brief jerks involving groups of muscles, is more common in juvenile-onset HD, where itmay be mistaken for a seizure. Like chorea, myoclonus may not be disabling or particularly distressing, butmay respond to treatment with clonazepam or divalproex sodium if treatment is necessary. Tics are brief,intermittent stereotyped movements such as blinking, nose twitching, head jerking, or transient abnormalpostures. Tics which involve the respiratory and vocal apparatus may result in sounds including sniffs,snorts, grunts, coughs, and sucking sounds. Patients may be unaware of vocal tics, but family members mayfind the incessant noises grating. They should be helped to understand that the tics are not under voluntary control. Tics generally do not by themselves require treatment, but may respond to neuroleptics,benzodiazepines, or SSRIs.
Epilepsy is uncommon, though not unheard of, in adults with HD, but is said to be present in 30% of individuals with juvenile-onset HD. A first seizure in an HD patient should not be attributed to HDwithout further evaluation as it may be indicative of an additional neurologic problem, such as a subduralhematoma sustained in a fall. The workup of a first seizure should include a complete exam, laboratorystudies to rule out an infection or metabolic disturbance, an EEG, and a brain imaging study. The treatmentof a seizure disorder in a person with HD depends on the nature of the seizures. In the juvenile HD patient,myoclonic epilepsy or other generalized seizures may suggest divalproex sodium as a first treatment choice.
Although seizure management in HD is not usually difficult, for the occasional patient seizure control isquite difficult to achieve, requiring multiple medications or specialized referral.
SWALLOWING DIFFICULTIES Dysphagia is, directly or indirectly, the most common cause of death in people with late stage HD, whetherthrough choking, aspiration, or malnutrition. Dysphagia results from impaired voluntary control of themouth and tongue, impaired respiratory control due to chorea, and impaired judgement, resulting in eatingtoo rapidly, or taking overly large bites of food and gulps of liquid. Dry mouth, which can be brought on byneuroleptics, antidepressants, and anticholinergics, may worsen the problem.
No medications are known to improve swallowing directly. Early referral to a speech-language pathologist will help to identify swallowing difficulties, and periodic reassessment can identify changes in swallowing ability and suggest appropriate non-pharmacologic interventions, such as a change in food consistency. Devices such as Eat slowly and without enlarged grips for silverware and nonslip plates with raised edges to prevent spilling may prolong independent eating. HD affected individuals should be instructed early in Prepare foods with appro- the disease, before the onset of dysphagia, to eat slowly and deliberately, to sit in an priate size and texture.
upright position during and after meals, to take small bites, and to clear the mouth of Eating may need to be food after each bite by taking sips of liquid.
Caregivers should know Individuals with dysphagia should avoid doing other activities while eating, in the Heimlich manoeuvre.
order to concentrate on chewing and swallowing. For instance, patients should not talkwhile eating, nor be distracted by television or ambient noise. Those who tend tohyperextend the neck due to chorea or dystonia should be encouraged and remindedto use a "chin-tuck" position. Drinking fluid through a straw may be easier than drinking directly from acup, and the use of a covered cup or mug, like a "sippy cup" used by young children, may prevent spillagedue to chorea. Grainy items, such as ground beef or rice, may irritate the pharynx and cause choking. Foodssuch as steak, which are hard to chew, should also be avoided, or ground to a pureé. Patients may havedifficulty adjusting to different textures of food, and may do better if they finish each item on the plate inturn.
In late HD, when even liquids may be difficult to swallow, the texture of food should be soft and smooth, and liquids may be thickened with an additive (see Appendix 3). For those patients who may beunable to follow instructions reliably, a caregiver can cut the food in advance, and ensure that each mouth-ful has been completely chewed and swallowed before the next bite is begun. Supervision throughout themeal may be necessary, and the family or caregiver should be taught to perform the Heimlich manoeuvre.
In some cases, eating eventually requires so much energy and concentration that the patient becomes tired and frustrated before consuming adequate amounts of food. Weight loss, very prolongedmealtimes or an inability to handle utensils may be the signal that he will need to be fed for at least part ofthe meal. Self-feeding may be prolonged by having the patient eat more frequent, but smaller meals, and byusing "finger foods." The transition to assisted feeding does not have to be all or nothing, as patients maystill be able to eat unassisted at certain times and be fed at other times.
Choking may decrease once self-feeding is stopped, because the caregiver will have greater control over the size and frequency of the bites. The caregiver should still promote eating slowly, and not talkingwhile eating, and should make sure the mouth is empty before each bite. With supervision, most patientsare able to assist with feeding and to take adequate amounts of food by mouth quite far into the illness.
However, before dysphagia and communication difficulties become severe, the issue of feeding tubes shouldbe discussed with the patient and family, to ensure that appropriate nutrition can be maintained throughoutthe illness. A gastrostomy tube can clearly improve nutritional status in a debilitated person with severedysphagia, and may prolong life. However, patients and families may not desire this intervention late in thecourse of HD. The question of whether to use a gastrostomy tube, and other end of life issues are discussedin the final section of chapter 6.
Weight loss is a common problem in Huntington disease. This is probably due in part to diminished foodintake because of dysphagia, fatigue, and depression. However many HD patients also require a large caloricintake to maintain their body weight. This may be simply due to the expenditure of energy through involun-tary movements, but there may be other metabolic reasons not fully understood. Two strategies can beemployed to increase the caloric intake of someone with HD: increase the number of meals, or increase thecalorie content of the food. The first goal can be achieved by eating five small meals a day or by adding highcalorie snacks such as milkshakes. The caloric content of the food can be increased by measures such asadding oil to soups, drinking cream instead of skim milk, adding margarine liberally as a condiment, andfocusing on easily eaten, high-calorie foods such as pasta with cream based sauce. Consultation with anutritionist can help in selecting the most appropriate foods and supplements to meet the patient's needs.
Regaining lost weight sometimes results in improved alertness and responsiveness, and often appears toreduce chorea as well. Maintaining hydration is also very important, particularly in the summertime inpatients who may not be able to request fluids. Cyproheptadine, an antihistamine, given as 4mg at bedtime,may help increase weight by stimulating appetite in some patients.
Dysarthria, a difficulty with the physical production of speech, results largely from impairment of voluntarymovement. Speech becomes slurred, dysrhythmic, variable in volume due to inconsistent breath support,and increasingly difficult to understand. Furthermore, just as patients donot always appreciate the presence or degree of chorea, some patients do not seem to be aware of distortions in their speech. For others, articulation Coping Strategies For
is a constant source of frustration. No medications are known to be helpful, and dysarthria may be worsened by agents which suppress chorea.
However, several interventions may enhance communication in these Allow the person enough time to answer patients. The listener must do everything possible to promote successful communication, beginning with allowing enough time. Many HD patients Offer cues and prompts to get the thought to be incapable of communication can be understood if the person started.
listener is patient enough. Patients may need to be moved to a quieter, Give choices. For example, rather than calmer environment, and urged to speak slowly. Patients can be asked to asking "what do you want for dinner?" spell difficult to understand words. A communication board can also be ask "do you want hamburgers or useful in some cases. A speech-language pathologist may be able to pro- Break the task or instructions down into vide additional insights and management strategies.
Dysarthria may be compounded by cognitive problems found in If the person is confused, speak more HD, such as word-finding difficulty, difficulty initiating speech, or diffi- simply and use visual cues to demon- culty completing a sentence. Even those with severe cognitive impair- strate what you are saying.
ments often respond to cues, such as asking for the size, shape or color of Ask the person to repeat phrases you an object. Even severely impaired patients may be able to respond accu- did not understand, or spell the words.
rately to a series of yes and no questions. If unsuccessful attempts at Alphabet boards, yes-no cards, or other communication become very frustrating, it may be better to take a break.
communication devices may be helpful.
The desire for social interaction generally remains, even in those withadvanced HD, so strategies for communication should be a priority.
Falls are common in persons with HD, and can be a source of significant morbidity. Usually seen more inthe moderate to advanced stages, they often result from the combination of spasticity, rigidity, chorea, andloss of balance. Pharmacotherapy to prevent falls could include treatment of chorea, rigidity, spasticity anddystonia, while minimizing the use of drugs such as neuroleptics and benzodiazepines, whose side effectsinclude sedation, ataxia, or parkinsonism. Most efforts at prevention, however, involve not drugs, butmodification of the environment and behaviour of the patient. Occupational therapists and physiotherapistscan instruct patients in how to sit, stand, transfer, and walk more safely. Installing handrails in key loca- tions, and minimizing the use of stairs can help to reduce falls. Some families convert a ground floor officeor den into a bedroom. Furniture such as tables and desks, particularly items with sharp corners, should bearrayed along the periphery of the room, where they will present less of an obstacle. Floors should be car-peted to lessen the impact when falls do occur. Patients who fall out of bed may have a mattress placedbeside the bed at night, or may sleep on a mattress placed directly on the floor.
HD patients will eventually become unable to walk and will need to be transported in a wheelchair.
A weighted and padded chair, perhaps with a wedge to keep the hips tilted, or a pommel between the legs,may minimize the chance of a severely choreic or dystonic patient falling or sliding out, or knocking overthe chair (see Appendix 3). Use of a wheelchair is not an all or nothing proposition. Mobility may beextended by using the wheelchair for longer excursions and using other assistive devices such as a walker forshorter distances, or in the home. Walkers with front wheels may be particularly useful when rigidity or lossof balance is a problem. Patients who are particularly prone to falls sometimes wear helmets, or elbow andknee pads to minimize injury. Physiotherapy may also help by teaching patients how to minimize injury in afall and how to get up again after a fall.
GENERAL SAFETY MEASURES A number of other environmental interventions may reduce the risk of injury. Patients who smoke shoulddo so in a room without flammables, such as rugs, curtains and overstuffed furniture. Patients may need tostop using sharp knives and to switch to microwave cooking to prevent burns and spills. Falls in the bath-room are particularly dangerous, but there are a variety of assistive devices that can be installed. Consulta-tion with a visiting nurse, or a visit from a physiotherapist or occupational therapist may be very helpful forany mid-stage HD patient being cared for in the home. A sample home visit consultation form is providedin Appendix 4.
The Cognitive Disorder The cognitive disorder in HD is considered a "subcortical" syndrome and usually lacks features such asaphasia, amnesia, or agnosia that are associated with dementia of the Alzheimer's type. The most prominentcognitive impairments in HD involve the so-called "executive functions"—abilities such as organization,regulation and perception. These fundamental abilities can affect performance in many cognitive areas,including speed, reasoning, planning, judgement, decision making, emotional engagement, perseveration,impulse control, temper control, perception, awareness, attention, language, learning, memory and timing.
Several studies have suggested that cognitive and behavioural impairments are greater sources of impaired functioning than the movement disorder in persons with HD, both in the work place and at home.
In addition, family members most often report that placement outside the home is initiated because of cogni-tive and behavioural deterioration rather than motor symptoms.
This chapter provides an overview of cognitive impairments and the related behaviour problems that typically accompany HD. In addition, compensation and adaptation strategies are provided, which physiciansmay recommend to patients, families and other professionals.
Difficulties in planning, organization, sequencing and prioritizing can affect responsibilities at home and atwork. Daily tasks, such as attempts to follow a recipe, to maintain a daily planner, to complete a list of house-hold errands, to develop a meeting agenda, or to apply for social security benefits, become daunting.
Many early-stage HD patients complain of problems with organization and report that they just "can't get things done." There are several ways to compensate for poor organization, which can be instituted early inthe disease. Routines should be established at work or in the home so that the environment can providestructure and organization. Activities should be organized so that each day is basically the same. For example, 7:00 shower, 7:30 breakfast, 8:00 take bus to work, 8:30 check mail, 9:30 dictate letters, 10:00 coffee, 10:30staff meeting, 12:00 lunch, 1:00 return phone calls, 2:30 review accounting, 4:00 open meeting to schedulewith customers, 5:00 take bus home, 6:00 dinner, 7:00 family time with kids, 8:30 time with spouse, 9:30read, 10:00 lights out. A central location could be established for posting a daily schedule. Persons whonever before used daily planners or computer calendars may need to start. A centralized message center canbe used to make lists and organize tasks to be accomplished each day. Additional strategies for dealing withpoor organization are offered in Table 6.
LACK OF INITIATION Table 6:
Coping Strategies For Planning
And Decision Making
Some family members complain that the person with HD"just sits around all day and won't do anything." Regula-tion of behaviour involves getting started, maintaining Rely on routines, which can be easier to initiate or the desired behaviour and stopping unwanted behaviours.
continue without guidance.
The initiation, or starting of an activity, conversation or Make lists which help organize tasks needed to do an activity.
behaviour is often compromised in HD. A lack of initia- Prompt each step of an activity with external cues tion is often misinterpreted as laziness, apathy or lack of (routine, lists, familiar verbal cues).
interest, and may be a reason for poor performance at Offer limited choices and avoid open ended ques- work. Once started, persons with HD may be able to execute the behaviours adequately (i.e., compute taxes, Use short sentences with 1–2 pieces of information.
calculate sales, administrate employees, teach school),but may be unable to organize and initiate the behavioursat the appropriate time. External initiation often helpsthe person with HD remain active and participate in both social and work activities. Keeping a daily routine can minimize the need for internal initiation. Maintainingthe desired behaviour is usually less of a problem for persons with HD. If this aspect of regulation is im-paired, however, the HD patient may be unable to regulate ongoing behaviours in an appropriate manner.
Perseveration, or being fixed on a specific thought or action, can occur when behaviours are inadequatelyregulated by the brain. Spouses often report that patients become behaviourally rigid, and tend to get stuckon an idea or task. Established routines and gentle reminders of changing tasks can help avoid problems.
An activity that is atypical for the established routine will be particularly stressful and challenging for theperson with HD. For instance, travel out of town, or a visit to the doctor or dentist, may disrupt a saferoutine. When shifting to a new task, help prepare the person with HD and allow plenty of time for him toadapt to the new idea. There is a delicate balance of how much preparation is needed. Telling of a change inplans too early can cause increased anxiety. Typically, inform the HD patient only one day prior to an eventor a few hours before. Allow plenty of time and frequent gentle cues to allow the shift to take place.
Some persons with HD experience difficulties with impulse control and may develop problem behaviourssuch as irritability, temper outbursts, sexual promiscuity and acting without thinking. Some degree ofimpulsivity and dysregulation of behaviours is quite common in HD. Some strategies to help family membersand caregivers cope with impulsivity are addressed below.
Coping Strategies For Impulsivity
Since the person with HD cannot control their responses, a predictable daily schedule can reduce confusion, fear and, as a result, outbursts.
One of the most typical complaints we hear from HD It is possible that a behaviour is a response to something families is concern about irritability and temper outbursts.
that needs your attention. Don't be too quick to discount it These signs can be present for a couple of reasons. First, it as an outburst.
is important to assess for depression when increased Stay calm. This will help you remain able to think and not irritability is reported. Oftentimes, irritability and temper react emotionally and impulsively yourself. In addition, outbursts diminish when a mood disorder is treated. Many staying calm may help the person calm down.
times, however, irritability or outbursts remain even in the Let the person know that yelling is not the best way to get absence of a mood disorder.
your attention and offer alternative methods for getting Examination of the underlying causes of irritability your attention.
Remember, although the things being said are hurtful or and temper outbursts is helpful in diminishing the fre- embarrassing, generally the person is not doing this quency and severity of these behaviours. Persons with HD intentionally. This is the HD talking, not your loved one.
are continually challenged by previously routine tasks or The person may be remorseful afterward. Be sensitive to activities that are experienced as overwhelming. HD his efforts to apologize.
results in a progressive loss of abilities that often "sneak Do not badger the person after the fact. It won't help.
up" on persons with HD. Several patients have confided Remember, this lack of control, likely, is not by choice.
that "I didn't realize I could no longer do it." Close atten- Medications may be helpful for outbursts and sexually tion should be paid to the signals, verbal or nonverbal, inappropriate behaviour. Talk to your physician.
that the patient is upset or wanting something, so thatthey do not get to the stage of exploding before theyreceive attention.
Knowledge of the person and sensitivity to his needs means that some situations can be anticipated and potential frustration defused. It may be possible to identify situations which trigger frustration andeither avoid them or provide diversional activities. An awareness of the person's capabilities is very impor-tant, so that he is encouraged to be as independent as possible and allowed to take risks without riskingconstant exposure to failure.
Although this encouragement to maintain independence is not always possible at work, it is critical to encourage in the home. The person with HD should be encouraged to do things for himself and to participate in primary decision-making as long as possible, except perhaps in situations where safety is anissue (i.e. driving or cooking). Family members should be responsible for providing a safe environment sothat no person is ever in danger. Remove dangerous implements, such as guns, from the house and haveemergency numbers near the telephone.
Listed below are some general strategies for families to employ to minimize irritability and some coping skills for temper outbursts.
Coping Strategies For Irritability
PERCEPTUAL PROBLEMS And Temper Outbursts
HD causes deficits in spatial perception. The mental ma- Assess your own expectations regarding the HD nipulation of personal space is impaired, even early in the affected individual. A family member may be unwilling disease. For instance, the judgement of where the body is in or unable to accept the patient's new limitations.
relation to walls, corners or tables may be disturbed, resulting Try to keep the environment as calm and controlled as in falls and accidents. Precautions might include carpeting the floors and removing furniture with sharp corners to the Speak in a low, soft voice. Avoid confrontations and periphery of the room, where it will be out of the patient's ultimatums. Sit down and keep hand gestures quiet.
path. Behaviour problems reported by family members are Try to identify circumstances which trigger irritability and temper outbursts and avoid them.
often due to another kind of impaired perception, unaware- Redirect the HD person away from the source of anger.
ness of changes due to HD, which can lead to challenges in Learn to respond diplomatically, acknowledging the providing care.
patient's irritability as a symptom of frustration.
Denial is commonly considered a psychological inability to cope with distressing circumstances. We oftensee this in situations such as the loss of a loved one, a terminal disease, or a serious injury. This type ofdenial typically recedes over time as the individual begins to accept their losses. Individuals with HD oftensuffer from a more recalcitrant lack of insight or self-awareness. They may be unable to recognize their owndisabilities or evaluate their own behaviour. This type of denial is thought to result from a disruption of thepathways between the frontal regions and the basal ganglia. It is sometimes called "organic denial," oranosognosia, and is a condition that may last a lifetime. We recommend that "unawareness" be used todescribe this type of denial in HD to distinguish it from the more familiar kind and to avoid thinking ofpatients with HD as suffering from a purely psychological problem.
Unawareness often plays a significant role in seemingly irrational behaviour. At first unawareness may be beneficial because it keeps the individual motivated to try things and to avoid labelling himself. In this way it may prevent demoralization. On the other hand, unawareness may lead to anger and frustrationwhen the individual cannot understand why he cannot work or live independently. The HD patient withunawareness sometimes feels that people are unjustifiably keeping him away from activities that he coulddo, such as driving, working, or caring for children, and may attempt to do these things against the advice offamily and friends. This type of unawareness can become dangerous.
Organic denial is also an issue for health professionals, friends, and family members, who may delay making the diagnosis or keep the diagnosis from the affected individual because they are concerned that he"cannot handle it." Some people interpret the unawareness as a sign that the individual does not want toknow. We have not found that talking about HD to a person with unawareness will cause negative conse-quences.
In our clinical experience, organic denial is not easily amenable to treatment or change. Neverthe- less, there are different degrees of unawareness. It may be that the person can talk about her problems, butnot acknowledge that she has HD. In such a case, one might try to address the problems while avoidingdiscussion of the diagnosis. Noncompliance with therapy or nursing care should not automatically be interpreted as intentional. It may be helpful to Coping Strategies For
develop a contract that includes incentives for compliance. Denial can thus be sidestepped, while behavioural goals remain the same. For example, thegoal may be to convince an unsafe driver to stop, rather than to accept the Do not make insight the central goal.
diagnosis, or acknowledge why he must stop driving.
A person may be able to talk about his problems without acknowledging Unawareness will not always respond to interventions, and a person with HD may never seem to "accept" the There are many different types of attention. In persons with HD, simple attention often remains intact. In contrast, sustained or complex types of Counselling may help someone with attention become impaired by HD. For instance, most persons with HD will HD come to terms with the diagnosis experience difficulty with what is called "divided attention," or the capacity but may have little impact on specific to do two things at once. For most people, divided attention is impaired when we are tired, sick, or stressed. In HD, divided attention is compro- It may be helpful to develop a con- mised most of the time, regardless of extra stress. Consequently, a person tract, even a formal written agree- may complain that he can't "pay attention" as well as he used to.
ment, that includes incentives for Divided attention is needed to drive a car while listening to the compliance but "sidesteps" the radio, talking to the kids in the back seat, or talking on the cell phone.
When divided attention is impaired it is recommended that patients try todo only one thing at a time. For instance, an HD-affected person shouldturn off radios, television, and telephones, and limit conversations whilecooking dinner. When swallowing becomes a problem, mealtime distractions should be minimized and thepatient should concentrate on chewing and swallowing to limit choking.
Communication, or the transfer of information from one person to another, requires a complex integrationof thought, muscle control, and breathing. HD can impair all three of these functions. There are two mainaspects to communication: getting the information IN (understanding) and getting the information OUT(talking). Both of these aspects can be impaired by HD, making communication a difficult task.
The most prominent language difficulties in people with HD are (1) speaking clearly (articulation), (2) starting conversation (initiation), and (3) organizing what's coming in and going out.
Motor speech impairments are quite typical in HD. Persons with HD have even been accused of beingdrunk due to their sluggish speech articulation. A lack of motor coordination causes difficulties with enun-ciation and the breath control underlying speech.
IMPAIRED INITIATION OF SPEECH Word finding is often impaired, while knowledge of vocabulary is retained, because it takes the brain muchlonger to search and retrieve the desired object. Listeners sometimes fail to wait long enough for the brainto do its job.
In addition to speed limitations, the brain fails to regulate the sequence and amount of travelling information, resulting in impairments in starting and stopping. When language initiation is compromised byHD, techniques such as phrasing questions with alternate choice answers (e.g., yes or no; lasagna or spa-ghetti) may help someone get started or retrieve the desired response.
DISORGANIZATION OF LANGUAGE CONTENT In contrast to the basic impairments in language output, the basic capacity to understand language remainsrelatively intact in HD. Even in later stages of the disease, language comprehension may remain when theability to speak is significantly diminished. This fact is important to communicate to family members, staff atcare facilities and other professionals involved. Even if a patient cannot express herself, it is likely that shecan understand what is being said. Difficulties with word usage are rare in persons with HD, as are frankaphasia or impairments in semantic memory. The trouble that occurs in persons with HD is an inability toorganize the outgoing and incoming language, resulting in miscommunication. To aid the person with HDin organizing language output and input it is best to rely on short simple sentences and to assess under-standing frequently during important conversations.
LEARNING AND MEMORY The type of memory impairments found in HD consist mostly of difficulties in learning new information,and in retrieving acquired information, but not in storage of information. Problems occur in getting infor-mation in and out, due to the slowed speed of processing and the poor organization of information. Severalstudies have found that HD patients can demonstrate normal memory for information if offered in a recog-nition format. If, rather than asking "can you tell me what time your doctor's appointment is today?," oneinquires "is your doctor's appointment at 10:00 or 11:00 today?," persons with HD can often answer cor-rectly. Similarly, if patients with HD are given a long list of words to learn and arerequired to say the words back freely they perform poorly. But if they are given a list of words and asked to recognize which ones were on the earlier list they demonstrate good memory.
It has been observed that persons with severe amnesia such as that associated with Korsakoff's syndrome, herpes encephalitis, or Alzheimer's disease Keep day to day activities as can experience defective explicit memory, such as for names and dates, and routine as possible.
intact implicit, or unconscious memory, such as the ability to tie one's shoes. In Use schedules.
contrast, persons with HD typically have impairments in skills that depend on Use "to do" lists and reminders.
implicit memory. Driving, playing a musical instrument, or riding a bike are all Offer a list of choices to assist motor memories that can be considered implicit, or unconscious. HD impairs this with recall.
motor memory system, making HD sufferers reliant on more effortful conscious Provide cues to help with the memory systems to drive a car. Consequently, driving will take much more retrieval of information.
concentration and effort, resulting in increased fatigue and irritability.
Some recent findings have suggested that persons with HD have difficulty with the estimation of time. Forinstance, persons with HD may be less able to judge how much time has elapsed. Spouses often complainthat their once-punctual spouse becomes frequently late and mis-estimates how long activities will take.
Frequent reminders may be needed to keep on schedule. It is helpful to allow extra time and avoid timepressure when possible.
THE PROGRESSION OF COGNITIVE IMPAIRMENTS Although performance in IQ tests often remains within the normal range in the early stages of the disease,cognitive deficits are evident in speed of processing, cognitive flexibility (or the ability to shift topics readily)and the organization of complex information. The most sensitive indicator of early HD on the Mini-Mental State Examination is serial sevens (the ability to subtract 7 from 100 serially) and the most sensitivesubscale on the Mattis Dementia Rating Scale is initiation (the ability to begin and maintain verbal andmotor behaviours).
There exist few longitudinal studies of the cognitive decline in HD. Based upon the information available, speed, organization, and initiation of behaviour are impaired in early HD, constructional impair-ments worsen in mid-stage HD, and some abilities remain relatively spared (memory, language comprehen-sion) even in the later stages of the disease. Clinically, as the disease progresses, the severity of cognitiveimpairments increases and patients are often unable to speak or communicate their views in late stages.
The Psychiatric Disorder Patients with Huntington disease who have psychiatric disorders generally suffer from underdiagnosis andundertreatment. It is important to remember that psychiatric problems, particularly depression, are verycommon and very devastating in HD, but they are also very treatable. Relieving a depression in someone withHD may be the single most effective intervention a physician can perform.
Psychiatric disturbances in HD are varied. Some patients suffer from conditions such as Major De- pression, Bipolar Disorder, or Obsessive-Compulsive Disorder which are specific well-described syndromes,found in all sorts of patients. Many, if not most people with HD also experience less well defined, non-specificchanges in personality and mood, such as irritability, apathy, or disinhibition. Most of these psychiatric prob-lems are believed to be related directly to the central nervous system injury caused by HD. This issue isdiscussed further in the chapter on cognition.
SPECIFIC PSYCHIATRIC DIAGNOSES "Who wouldn't be depressed if they had HD?" Actually, research and clinical experience shows that manyHD patients are not depressed, and are able to adapt gradually to having HD. Nonetheless, even severedepression in someone with HD is often explained away as an "understandable" reaction, therefore notrequiring additional treatment. This potential for overinterpretation exists in a variety of other serious medicalconditions such as AIDS, stroke, and Alzheimer's disease, which have a high comorbidity with depression. Infact, those patients who have a depressive syndrome, even when the depression is "understandable," and evenwhen there are clear triggers, usually respond to standard treatments, including medications and psycho- therapy. Because depression in HD appears directly related to the brain disease, pharmacotherapy is usuallyindicated.
Major Depression is a clinical syndrome, a constellation of signs and symptoms which, taken to- gether, suggest the diagnosis. Use of diagnostic criteria helps to distinguish major depression from demorali-zation, transient changes in mood caused by negative life events, such as bereavement, and from some ofthe symptoms of HD itself, such as weight loss, trouble with concentration, and apathy. Patients with MajorDepression have a sustained low mood, often accompanied by changes in self-attitude, such as feelings ofworthlessness or guilt, a loss of interest or pleasure in activities, changes in sleep, particularly early morningawakening, and appetite, loss of energy, and hopelessness. Depressed patients often feel worse in the morn-ing than in the afternoon.
In severe cases of depression, patients may have delusions or hallucinations, which tend to match their depressed mood. A patient may hear voices berating him or urging him to commit suicide, or mayhave the delusion that he will be going to jail, or that he has killed his family. Depressed patients oftendisplay psychomotor retardation, a slowing of speech and movement as a result of depression. In extremecases they can appear stuporous or catatonic.
It is important to remember that because depression is a syndrome, with various symptoms and manifestations, the presenting complaint may be Signs And Symptoms
something other than a low mood. For example a depressed patient may complain of insomnia, anxiety, or pain, with each problem only a symptomof the depression which is the underlying cause. It is vital to get the whole Depressed or irritable mood story, because symptomatic treatment for any of these complaints, e.g.
Loss of interest or pleasure in sleeping pills, tranquilizers, or narcotics, could be worse than no treatment Change in appetite, or weight loss A specific complaint of depressed mood is not necessary to make Insomnia or hypersomnia the diagnosis if the patient has the other symptoms. In fact patients with HD often have trouble identifying or describing their emotional state.
Feelings of worthlessness or guilt Depression in such a patient may be characterized by changes in sleep or Impaired concentration appetite patterns, agitation, tearfulness, or a drop-off in functional abilities.
Thoughts of death or suicide In such circumstances the diagnosis should be considered.
In evaluating an HD patient with depression the physician also Feelings of hopelessness needs to consider whether some physical problem, other than HD, might be Social withdrawal Psychomotor retardation or agitation the cause. The patient's medical history should be reviewed for conditionssuch as hypothyroidism, stroke, or exposure to certain drugs associated with (Based on DSM-IV criteria) mood changes, such as steroids, reserpine, beta-blockers, and particularlyalcohol.
PHARMACOTHERAPY OF DEPRESSION Depressed people with HD can usually be treated with the same agents as any other patient with depres-sion, but certain factors may make some drugs easier to use. Many new medications have become availablesince the first edition of the Physician's Guide and the tricyclicantidepressants, while highly effective, should no longer be consid- ered the standard first-line choice. Instead, the physician should Key Points In The Treatment
consider the Selective Serotonin Re-uptake Inhibitors (SSRIs), such as sertraline (Zoloft), paroxetine (Paxil), fluoxetine (Prozac), and fluvoxamine (Luvox). These offer the advantages of low side Avoid overinterpretation of symptoms.
Depression is very common in HD. Have a low effect profile, once-a-day dosing, and safety in the event of over- threshold for diagnosis and treatment.
dose. Of these drugs, fluoxetine has a much longer half-life. If a HD patients are sensitive to side effects. Start patient develops an unpleasant side effect it will take longer to medications at a low dose and increase gradu- wear off. On the other hand this may make it a good choice for patients who sometimes forget to take their medicine.
Ask about substance abuse.
The SSRIs are sometimes stimulating and most patients Ask about suicide.
should take them in the morning rather than at bedtime. Initial sideeffects may be GI upset or diarrhea, and increased anxiety or insom-nia (although, if they are part of a depression, these symptoms willeventually respond to the treatment). SSRI-induced insomnia may respond to 25–50mg of trazodone(Desyrel) qhs. A small number of patients will develop sexual problems on SSRIs, particularly anorgasmia orejaculatory delay. These symptoms are highly dependent on the dose. Some people have asserted thatSSRIs, particularly fluoxetine, cause violence or suicide in psychiatric patients. There is no valid evidenceto support this claim.
Patients with HD are sensitive to the potential side effects of CNS drugs. Any new drug should be started carefully, and increased gradually. Sertraline 25–50mg, paroxetine 10mg, or fluoxetine 10mg areappropriate starting doses. If well tolerated, the dose can be increased after a few days or a week to sertraline50–100mg, paroxetine 20mg, or fluoxetine 20mg. Most patients will respond to these doses, but sometimeshigher doses will be necessary. As we will discuss, SSRIs may also be particularly useful for some of the morenonspecific psychiatric symptoms found in patients with HD, such as irritability, apathy, and obsessiveness.
Other, newer antidepressants we have used with success in patients with HD include buproprion (Wellbutrin), venlafaxine (Effexor), and nefazodone (Serzone). These all require dosing several times a day.
A new formulation of venlafaxine, Effexor XR, may be given once a day, and nefazodone is sometimes givenin a single bedtime dose, despite the short half-life. It is often difficult for depressed patients, especiallythose with cognitive impairment, to adhere to a complex medication regimen. Therefore these drugs maynot be good first choices if there is no responsible family member who will help make sure that the patienttakes his medicine.
Tricyclic antidepressants (TCAs) such as Nortiptyline (Pamelor), Imipramine (Tofranil) or Amitryptiline (Elavil) remain an important class of drugs for depression in HD. They can be given once a day (usually at bedtime because of sedative properties). Common side effects of TCAs include constipation,dry mouth, tachycardia, and orthostasis. We tend to favour nortriptyline over the others because of therelatively low incidence of these side effects and because of the well-established range of blood levels whichhave been associated with efficacy. It is not necessary to reach the target blood level if the patient hasalready responded to a lower dose, but the availability of meaningful blood levels for the TCAs can serve asa useful check of compliance, and a reassurance that a patient's dose is optimal. Since TCAs can worsenconduction delays, an EKG is indicated prior to treatment if the patient's cardiac status is unknown. TCAsare extremely dangerous in overdose. As little as a week's supply may be fatal if taken at once. They are apoor choice in patients with a history of deliberate overdoses and may have to be dispensed only a few pillsat a time if this is a concern.
Medications Used To Treat Depression
insomnia, diarrhea, GI upset, restlessness, similar, more sedation dry mouth, blurry vision, tachycardia, sedation sedation, nausea, dry mouth, dizziness, seizures, agitation, dry mouth, insomnia, nausea hypertension, nausea, headache, constipation If the patient's depression is accompanied by delusions, hallucinations, or significant agitation, it may be necessary to add an antipsychotic medication to the regimen, preferably in low doses to minimizethe risk of sedation, rigidity, or parkinsonism. If the neuroleptic is being used for a purely psychiatric pur-pose, and is not required for suppression of chorea, the physician may want to prescribe one of the newer agents such as risperidone (Risperdal), olanzepine (Zyprexa), or quetiapine (Seroquel). These drugs mayhave a lower incidence of side effects and appear to be just as effective. Among the older neuroleptics, highpotency agents such as haloperidol (Haldol) or fluphenazine (Prolixin) tend to be less sedating, but causemore parkinsonism. Lower potency agents such as thioridazine (Mellaril) may aid with overactivity andsleeplessness, but tend to be constipating and can cause orthostasis.
Benzodiazepines, particularly short acting drugs such as lorazepam (Ativan) may be another good choice for the short-term management of agitation. In any case neuroleptics and benzodiazepines used foracute agitation should be tapered as soon as the clinical picture allows.
Some Antipsychotic Medications Used In HD
sedation, parkinsonism, dystonia, akathisia, hypotension, constipation, dry mouth, less parkinsonism, less dystonia less parkinsonism, less dystonia less parkinsonism, less dystonia Electroconvulsive therapy (ECT) has also been found effective in depressed patients with HD. This treatment should be considered if a patient does not respond to several good trials of medication, or if animmediate intervention is needed for reasons of safety. For example a severely depressed patient may berefusing food and fluids, or may be very actively suicidal. ECT may be particularly effective in treatingdelusional depression.
Depressed patients should always be asked about substance abuse. Substance abuse, particularly of alcohol, can be both a consequence or a cause of depression, makes treatment difficult or impossible if notaddressed, and significantly increases the risk of suicide.
Depressed patients should always be asked about suicide, and this should be regularly reassessed. It is amisconception that suicidal patients will not admit to these feelings. The question should be asked in a non-intimidating, matter-of-fact way, such as "have you been feeling so bad that you sometimes think life isn'tworth living?" Or, "have you even thought about suicide?" If the patient acknowledges these feelings, the clinician needs to ask more questions to evaluate their severity and decide on the best course of action. Are the feelings just a passive wish to die or has thepatient actually thought out a specific suicidal plan? Does the patient have the means to commit suicide?Has she prepared for a suicide, such as by loading a gun or hoarding pills? Can the patient identify anyfactors which are preventing her from killing herself? What social supports are present? Some patients,although having suicidal thoughts, may be at low risk if they have a good relationship with their doctor,have family support, and have no specific plans. Others may be so dangerous to themselves that theyrequire emergency hospitalization.
Although there have been cases of non-depressed patients with HD harbouring chronic suicidal feelings, we feel that most, if not all, suicidal patients with HD suffer from Major Depression and can betreated successfully. So as not to miss such cases, it is helpful to think of all patients with HD who aresuicidal as depressed until proven otherwise. If the clinician is unsure, the patient should be treated pre-sumptively. This is not to say that a person with HD, particularly early in the course of the disease may notexpress a fear of becoming helpless one day, or a desire not to live past a certain degree of impairment. Aphysician should listen supportively to these concerns, realizing that most patients will be able to adapt ifthey are not suffering from depression.
While depression is the most common psychiatric problem in HD, a smaller number of patients will becomemanic, displaying elevated or irritable mood, overactivity, decreased need for sleep, impulsiveness, andgrandiosity. Some may alternate between spells of depression and spells of mania with times of normal moodin between, a condition known as bipolar disorder. Patients with these conditions are usually treated with amood stabilizer. Lithium is probably still the most popular mood stabilizer for people with idiopathic bipolardisorder, but we have not found it to be as helpful in patients with HD. It is not known why this is the case.
Lithium has a narrow therapeutic range, particularly in patients whose food and fluid intake may be spotty,but there may be some other aspect to the mood disorders found in HD patients which make them poorlithium responders.
We recommend beginning with the anticonvulsant divalproex sodium (Depakote) or valproic acid (Depekene) at a low dose such as 125 to 250mg po bid and gradually increasing to efficacy, or to reach ablood level of 50–150mcg/ml. A dose of 500mg po bid is fairly typical, but some patients will require asmuch as several grams per day. Another anticonvulsant, carbamazepine (Tegretol), is also an effective moodstabilizer. This can be started at 100–200mg per day, and gradually increased by 100mg/day to reach aneffect or a therapeutic level of 5–12mcg/ml, which may require a dose of 800–1200mg/day. Therapeuticranges for these drugs were established on the basis of their anticonvulsant properties, so it is important toremember that a patient may show a good psychiatric response below the minimum "therapeutic" level (butgenerally should not exceed the maximum level in any case). Both drugs carry a small risk of liver functionabnormalities (particularly divalproex sodium) and blood dyscrasias (particularly carbamazepine), and so LFTs, and CBC should be routinely monitored every few months and clinicians should be alert for sugges-tive symptoms. Valproic acid may cause thrombocytopenia, and both drugs are associated with neural tubedefects when used during pregnancy.
Manic patients with HD who have delusions and hallucinations may require a neuroleptic, and patients who are very agitated may need a neuroleptic or a benzodiazepine for immediate control of thesesymptoms. As discussed for depression, the doctor may wish to prescribe one of the newer antipsychoticswhich have fewer parkinsonian side effects, such as risperidone, olanzepine, or quetiapine. In cases ofextreme agitation, a rapidly acting injectable agent, such as droperidol (Inapsine) or lorazepam may benecessary. Finally, ECT is known to be a very effective treatment for idiopathic mania and should be con-sidered when other treatments fail, or when the individual is extremely dangerous.
Medications Used For Mania In HD
Neuroleptics (see table 14) Divalproex sodium G.I. upset, sedation, tremor, liver toxicity, sedation, dizziness, ataxia, rash, bone marrow suppression Obsessions are recurrent, intrusive thoughts or impulses which are experienced as being senseless, at leastinitially. A compulsion is a repetitive performance of the same activity, a stereotyped routine which must befollowed, often in response to an obsession, such as handwashing because of an obsessive concern withgerms. Obsessions are usually a source of anxiety and the patient may struggle to put them aside, whereasthe acting out of compulsions generally relieves anxiety and may not be as strongly resisted.
True Obsessive-Compulsive Disorder (OCD) is rare in HD, but HD patients often display an obsessive preoccupation with particular ideas. Patients may worry about germs or contamination, or engagein excessive checking of switches or locks. Sometimes patients will become fixated on an episode of beingwronged in the past (e.g. fired from a job, divorced, driver's license revoked), and then bring it up con-stantly, or become preoccupied with some perceived need, such as a desire to go shopping, or to eat acertain food.
Serotonergic antidepressants are used to treat OCD and may ameliorate obsessions and compul- sions in HD patients that do not meet the criteria for the full syndrome. The use of the tricyclic antidepres- sant clomipramine (Anafranil) has largely been superceded by the SSRIs fluoxetine, sertraline, paroxetineand fluvoxamine (Luvox) which have milder side effects and lower lethality in overdose. Patients mayrequire higher doses than those needed for depression, e.g. 40–60mg of fluoxetine. For relentlessperseverative behaviour unresponsive to these agents, one might consider neuroleptics, keeping in mindthat the newer, atypical drugs may be better tolerated.
Schizophrenia and schizophrenia-like conditions are much less common than affective disorder in HD. Thenew onset of delusions and hallucinations should prompt a search for specific causes or precipitating factors,including mood disorders, delirium related to metabolic or neurologic derangements and intoxication withor withdrawal from illicit or prescription drugs.
Once these possibilities of mood disorder, drug intoxication, and delirium have been considered, neuroleptics may be employed for HD patients with schizophrenia-like syndromes. The doses used fortreatment of psychosis may be somewhat higher than those used for treatment of chorea. As mentionedbefore, if neuroleptics are not needed for the control of involuntary movements, patients may do better onnewer agents such as risperidone, olanzepine or quetiapine which do not cause as many extrapyramidal sideeffects. Some patients will respond completely and others only partly, reporting that "voices" have beenreduced to a mumble, or becoming less preoccupied with delusional concerns. Patients with delusions willrarely respond to being argued with, but a clinician may certainly express skepticism regarding a delusionalbelief and explain to the patient that it may be the product of a mental illness. Caregivers should be encour-aged to respond diplomatically, to appreciate that the delusions are symptoms of a disease, and to avoiddirect confrontation if the issue is not crucial.
Delirium, an abnormal change in a patient's level of consciousness, may result from a variety of toxic,structural or metabolic causes. Delirious patients may have waxing and waning of consciousness, may beagitated or lethargic, and frequently have disturbed sleep. Patients in the later stages of HD, are particularlyvulnerable to delirium. Common causes of delirium in HD include prescription medications, particularlybenzodiazepines and anticholinergic agents, alcohol or illicit drugs, and medical problems such as dehydra-tion and respiratory or urinary tract infections. It is important to ask about over the counter medicines suchas cold tablets and sleep aids, which patients and families may forget to mention. Subdural hematoma, dueto a recognized or unrecognized fall should also be considered if the patient suffers a sudden change inmental status. Delirium can also come about gradually as an underlying problem worsens. For example, adehydrated patient may no longer be able to tolerate his usual medication regimen.
Delirium can also be mistaken for a number of other conditions in HD. As mentioned previously, it may be accompanied by hallucinations or paranoia. Clinicians usually expect delirious patients to exhibitagitation or hyperarousal and may overlook the delirious patient who is somnolent or obtunded. Suchpatients may seem depressed to their families, but when questioned will not report a low mood.
Physicians should consider a diagnosis of delirium whenever confronted with an acute behavioural change in someone with HD and should review the medication list, examine the patient, and obtain neces-sary laboratory studies, including a toxicology screen if indicated. Identification and correction of theunderlying cause is the definitive treatment for delirium. Low doses of neuroleptics may be helpful inmanaging the agitation of a delirious patient temporarily.
PSYCHIATRIC SYMPTOMS NOT BELONGING TO ASPECIFIC DIAGNOSTIC CATEGORY Patients with Huntington disease may suffer from a variety of emotional symptoms which do not fit anyspecific psychiatric diagnosis, but may nevertheless be a source of distress and a focus of treatment includ-ing irritability, anxiety and apathy. Some of these symptoms are related to the disease itself, and others canbe seen as a response to changing circumstances, such as a patient who becomes anxious about going to themarket because her involuntary movements attract attention. Patients with HD may undergo personalitychanges, becoming irritable, disinhibited, or obsessional. In some cases these changes represent an accen-tuation, or coarsening of personality characteristics the person already had. Other times they will be aradical departure from the patient's usual state, which can be very distressing to families. Families should bereassured, as patients can usually be helped by better communication, environmental interventions, andjudicious use of medications.
Irritability is a common complaint from persons with HD and their families. It is often associated with adepressed mood, but may also result from a loss of the ability of the brain to regulate the experience andexpression of emotion. Irritability in persons with HD may take the form of an increase in the patients'baseline level of irritability, or there may be episodes of explosiveness as irritable responses to life eventsbecome exaggerated in intensity and duration. Other patients may not be irritable under most circum-stances, but will develop a kind of rigidity of thinking which will cause them to perseverate relentlessly on aparticular desire or idea, becoming progressively more irritable if their demands are not met. One woman,for example, insists on having ten or twelve varieties of juice in the refrigerator at all times and was mark-edly irritable during a recent visit to the clinic. Her husband had started the car to drive to the clinic andhad refused to go back into the house to get her another glass of juice. Hours later she was still dwelling onit and kept interrupting the interview to say that she wanted to go home to have a drink.
Irritability in HD may have a variety of triggers and exacerbating causes. It is important to under- stand it in context and avoid premature use of medications. One must first understand exactly what theinformant means by saying the patient is irritable or agitated. Does the patient appear restless? Is the patientyelling or verbally abusive? Is there potential for violence? Many factors can precipitate an irritable episode,such as hunger, pain, inability to communicate, frustration with failing capabilities, boredom, and changes inexpected routine. Family members and caregivers should learn to respond diplomatically, appreciating thepatient's irritability as a symptom. Confrontations and ultimatums should be avoided if the issue is notcrucial.
The environment should be made as calm and structured as possible. Some families achieve this more easily than others. Family settings in which there are children and adolescents, unpredictable workinghours, noise, or general chaos may lead to irritability and aggressiveness in persons with HD. Caretaker andfamily support groups can provide emotional support and are a forum for sharing strategies that membershave found useful in their own households.
When irritability is severe, or enduring, or is expressed physically, patients are often described as agitated. A great deal of overtreatment, particularly with neuroleptics, stems from continuous use of a drugfor an episodic problem. It is always necessary to revisit the situation and see whether the drug has actuallyreduced the frequency of outbursts. For episodic outbursts, success often results from combining drugtherapy with a careful analysis of the context and precipitants of the outburst.
Nevertheless, we have found a number of medications helpful in treating enduring irritability.
Patients may respond to antidepressants, particularly the SSRIs (sertraline, fluoxetine, and paroxetine) even if they do not meet all the criteria for major depression. The optimal doses for treating irritability are not known but one Coping Strategies For Irritability
should start at a low dose and increase gradually as in thetreatment of depression (see Table 13). These agents may Restructure the person's expectations and responsibili- be particularly useful when the irritability seems tied to ties to manage frustration. The environment should be obsessions and perseveration on a particular topic. As in the as calm and structured as possible.
treatment of depression, improvement may not occur for Respond diplomatically, acknowledging the irritability several weeks. Mood stabilizers such as divalproex sodium as a symptom. Confrontations and ultimatums should and carbamazepine have also been helpful and could be be avoided unless the issue is crucial.
administered as outlined for bipolar disorder (see Table 15).
Try to identify circumstances which trigger temper Low dose neuroleptics may be helpful, particularly the outbursts, and redirect the person away from the newer, "atypical" ones which have fewer side effects. Long- source of anger.
acting benzodiazepines, such as clonazepam (Klonopin), Family and caretaker support groups can provide starting at low doses, e.g. 0.5mg/day, have also been helpful.
valuable emotional support and are good places to The clinician must carefully monitor patients treated with learn and share effective strategies.
these agents, as overdosing can lead to falls or aspiration.
Coping Strategies For
Apathy is common in HD and is probably related to frontal lobe dysfunc- tion. Apathetic patients become unmotivated and uninterested in theirsurroundings. They lose enthusiasm and spontaneity. Performance at Use calendars, schedules and routines work or school becomes sluggish. The symptom of apathy can be very to keep the person busy.
troubling to families, if they see the active person they knew slipping Do not interpret lack of activity as away. It can be a source of conflict for caregivers, who know the person is physically capable of activities but "won't" do them.
Patients may not be able to initiate Families need much education and support in this regard and activities, but may participate if encour- should learn to practice a combination of exhortation and accommoda- aged by others.
tion. While apathetic patients have trouble initiating actions, they will Gently guide behaviours, but accept often participate if someone else suggests an activity and works along with them to sustain energy and attention. For example, a man with HD hadalways loved fishing, but when his brother came to take him fishing for his birthday he wanted to stay homein front of the television. The brother insisted, and when they left the house, he had a good time fishing allday. When he returned, he immediately turned the television back on.
Apathy can be hard to distinguish from depression. Apathetic patients, like those with depression, may be sluggish, quiet, and disengaged. They may talk slowly, or not at all. By and large apathetic patientswill deny being sad, but in distinguishing the two it is important to ask not only about the patient's mood,but about other depressive symptoms as well, such as a change in sleeping or eating patterns, feelings ofguilt, or suicidal thoughts. Neuroleptics and benzodiazepines can cause or worsen apathy. The need forthese medications should be reexamined if the patient is apathetic.
Depressed patients with apathy should be treated aggressively for their depression, which may cause the other symptoms to remit. It can be very difficult to distinguish depression from primary apathy, butpatients with primary apathy sometimes respond to psychostimulants such as methylphenidate (Ritalin),pemoline (Cylert) or dextroamphetamine (Dexedrine). These medicines are highly abusable and mayexacerbate irritability. They should be used with caution. It may be more prudent to make a trial of a non-sedating antidepressant, such as an SSRI, first even if the patient does not seem to meet the criteria fordepression, as these agents have also occasionally been helpful.
Patients with HD are vulnerable to anxiety because of life circumstances, but also because of physical changes in the brain. Patients may develop a social phobia related to embarrassment about visiblesymptoms. As thought processes become less flexible, patients may be made anxious by trivial departuresfrom the usual routine. Patients may worry for days in advance about what to wear when going to thehairdresser or whether to attend a family function.
In addressing anxiety, attempts should be made to decrease the complexity of the patient's environ- ment. Stopping a job that has become too difficult may result in a remarkable decline in symptoms. Assist-ing the caregiver in establishing a predictable routine for the patient is helpful. Some caregivers find ituseful to refrain from discussing any special events until the day before they are to occur. Patients who arevery fearful of going to the doctor may need to be told only that they are going on an errand until theyreach the clinic.
Some patients will not improve with counselling and environmental interventions and will require pharmacotherapy. The clinician should first assess whether the anxiety is a symptom of some other psychi-atric condition, such as a major depression. Patients with obsessive-compulsive disorder may be madeanxious by obsessions about danger or "germs," or if their rituals are interrupted.
Panic disorder, although uncommon in HD, is a highly treatable condition. It is characterized by the acute onset of overwhelming anxiety and dread, accompanied by physiological symptoms of rapid heartbeat,sweating, hyperventilation, lightheadedness, or paraesthesias. Panic attacks usually last only fifteen ortwenty minutes, may begin during sleep, and may result in syncope. Suspected panic attacks require a goodmedical work-up, because most of the other possible explanations for the symptoms represent highly danger-ous conditions. Once these other causes have been ruled out, the usual treatment consists of SSRIs, some-times temporarily supplemented with benzodiazepines. SSRIs are usually mildly stimulating and may need tostart at a lower dose than that used for depression.
Benzodiazepines should be used judiciously in anxious persons with HD because of the vulnerability of these patients to delirium and falls and because of their potential for abuse, especially in patients whosejudgement may already be impaired. PRN medications may have to be controlled by a family member. Somepatients will respond to the non-benzodiazepine anxiolytic buspirone, which can be started at 5mg two tothree times per day and advanced to 20–30mg per day in divided doses.
SEXUAL DISORDERS Many patients with HD become uninterested in sexual activity. Others may continue to enjoy healthy sexual activity well into the course of the illness. Occasional patients may desire and pursue exces-sive sexual activity or engage in inappropriate sexual behaviours, such as public masturbation, or voyeurism.
The spouse, usually the wife, may be distressed and fearful because the individual with HD may becomeaggressive if sexual demands are not met. Spouses may be afraid to talk about the problem unless inter-viewed alone.
Interventions are difficult in these circumstances, probably because of the patient's impaired judge- ment and the strength of the drive. Open communication about sex between the doctor and the family canhelp to destigmatize this sensitive topic. With open discussion among the parties, distressing sexual behav-iours can sometimes be adapted into more acceptable acts. Patients engaging in these behaviours should beassessed and treated for comorbid conditions, such as mania. We have found antiandrogenic therapy helpfulin a few of these cases.
Other Issues All patients with HD eventually lose the ability to drive. This can be a severe blow for some patients, who seedriving as a sign of competence and a way of maintaining independence. In many cases, patients, with thehelp of their families, will realize the time has come and will voluntarily stop driving, often before their physi-cian has come to this conclusion. Other times, however, the issue of driving can become a source of conten-tion between patients, families, and physicians.
People with HD can be divided into groups on the basis of their driving abilities. Some mildly affected patients may have no significant problems and simply need to remain alert and not drive when very tired, afterdrinking, or under hazardous conditions. Most moderately to severely affected patients are not safe behind thewheel. A large number of patients occupy the middle ground; they may have mild symptoms, but the safety oftheir driving is uncertain. The physician should ask family members who have driven with the patient fortheir impressions, and should inquire about recent accidents and traffic citations, including those that were"someone else's fault." Some patients minimize their disability. A formal driving evaluation, at an occupa-tional therapy or rehabilitation centre may be available and can help both physician and patient by providingobjective information about the individual's performance.
In a situation in which a patient has become a hazardous driver and is unwilling to stop, or lacks insight into the degree of impairment, the doctor must intervene forcefully for the protection of the patientand others. We have found it useful at such times to give the patient a "doctor's order" rather than a sugges-tion, and to tell the patient that the instruction to stop driving will be documented in the record.
Some provinces may require physicians to notify the appropriate government department if a patient is no longer safe to drive. Family members can report a patient who is dangerous and will not listen to reason.
This is a very unpleasant responsibility, but it must be shouldered. In some provinces, these reports may bemade anonymously at times, to preserve harmony.
Smoking sometimes becomes a problem for people with HD, for two reasons. Changes in the person'sbehaviour related to disinhibition, personality changes, and perhaps boredom may turn smoking into aconsuming passion, leading to irritability and even violence if thwarted. Simultaneously chorea, impairmentof voluntary movements, impaired judgement, and diminished capacity for self observation may make theact of smoking unsafe. A variety of approaches have been helpful in decreasing the behaviour and improv-ing safety. Non-pharmacologic interventions include the establishment of smoking schedules and generalsafety measures such as ensuring that the patient does not smoke in bed, limiting smoking to rooms withoutrugs, and use of adaptive devices, such as a flexible tube smoker or a "smoker's robot," available throughrehabilitation supply and safety product catalogs (see Appendix 3).
We have also used nicotine patches with some success. The goal is not necessarily to wean the patient completely off cigarettes or patches, but to decrease the drive for cigarettes, and the periods ofnicotine withdrawal, which may worsen irritability. A variety of the antidepressant buproprion has alsorecently been marketed for use in smoking cessation and may be worth a try.
Sleep disturbance is a common problem in Huntington disease, and can be due to a variety of causes. Acomplaint of sleeplessness may be due to a mood disorder, either depression, or, less commonly, mania. Inthese cases, treatment of the mood disorder should lead to a normalization of sleep. The clinician shouldconduct a careful interview and speak to the patient's family to rule out this possibility.
Good sleep hygiene is also important. Patients who do not have enough to do, and whose days are insufficiently structured may develop a reversal of the sleep-wake cycle in which they nap most of the day,and are then awake at night. This pattern tends to reinforce itself and can be hard to interrupt. Helpfulstrategies include sleeping consistently in a room which is not used for wake-time activities, having a regularbedtime and waking time, and enrolling in a day program, which keeps the patient occupied and preventsdaytime napping. In the later stages of illness, patients may have an increased need for rest and daytimenapping may be entirely appropriate, as long as the patient is sleeping at night.
Some patients will require pharmacologic treatment of their insomnia. We would caution against long-term use of benzodiazepine or barbiturate hypnotics because of the potential for tolerance, depend-ence, and delirium and usually prefer to use a small dose of a sedating antidepressant such as trazodone(Desyrel), beginning at 25–50mg and increasing to about 200mg as necessary. Sedating tricyclics such asdoxepin (Sinequan) or amitriptyline (Elavil) can also be employed, but are highly dangerous in overdose.
It is not entirely true that chorea ceases when patients are asleep. Sleep studies conducted in patients with refractory insomnia have suggested that some HD patients have restless sleep because of alarge amount of involuntary movements at night. The patient himself will often be unaware of these nighttime movements, but they will often be reported by the spouse or caregiver. A small dose of fluphena-zine, haloperidol (0.5–2mg) or clonazepam (0.5–1mg) at bedtime, may suppress the movements sufficientlyto allow more restful sleep. Polysomnography or referral to a sleep disorder center may be helpful in thesedifficult cases.
Painful leg cramping caused by dystonia and spasticity can also disrupt sleep. Treatment with a muscle relaxant, such as baclofen may relieve the problem.
Most patients with advanced HD are incontinent, although this may be minimized with regular toileting.
Although urinary urgency, leading to intermittent incontinence may occur earlier in the course of thedisease, this is not a typical finding, and should be evaluated further before attributing it to HD alone.
Causes may include neurogenic bladder, urinary tract infections, urinary retention due to anticholinergicdrugs or tricyclic antidepressants leading to overflow incontinence, sedation or immobility caused byneuroleptics or sedatives, depression, dementia, or mechanical problems. Urologic consultation may behelpful in defining the nature of the bladder dysfunction and obtaining specific recommendations.
The progressive nature of Huntington disease will eventually force patients to retire from employment.
Unfortunately, many patients' job performance will already have begun to deteriorate before they havereceived a diagnosis, or before they have made the connection between HD and the problems they arehaving at work. The actual difficulty is most often a problem of organization, flexibility, and the speed ofmental information processing, but the patient may appear careless or lazy, may be irritable at work, or mayeven be suspected of being intoxicated. This may lead to an individual being disciplined, passed over forraises or promotions, or even fired for cause when in fact the problem is a medical disability due to HD.
Therefore, early identification of HD-related problems at work is very important, for the purposes of securing accommodations at work, and eventually disability. There may also be issues of work safety. Aphysician or social worker may be able to help the individual inform superiors at work of the nature of theproblem, decide when to take retirement, and navigate the disability application process. In our experience,many employers are sympathetic once informed, and have provided less stressful work environments andassistance with disability retirement.
We have included a sample disability letter in Appendix 5. HD is a complex condition and the patient may be unable to work, but may not have a single sign or symptom which, by itself, would qualifyher for disability. Therefore, disability letters must be comprehensive, must stress functionality, and shouldinclude specific examples of dysfunction at work. Because of the particular nature of the dementia found inHD, routine IQ test scores may not be relevant to the level of impairment because they do not reflect the organizational and task-switching problems found in Huntington disease. Tests specifically directed towardexecutive function will better identify HD-related cognitive deficits.
END OF LIFE ISSUES It is important to discuss issues related to the end of life before someone with HD loses the ability to communicate. By discussing the expected changes in advance patients can plan for the support that theyand their families will need, and can have a discussion with their family and physicians about which medicaltreatments and interventions they think they would like to undergo, and which they would prefer to havewithheld when they reach the late stages of the disease. By the late stages of HD affected individuals willhave little control over voluntary movements and may not be able to walk, talk, or eat. Chorea may besuppressed, or may be severe. Death, when it comes, is usually due to the consequences of the immobility,general debilitation, and malnutrition. Pneumonia, and heart failure are typical immediate causes of death.
Huntington disease patients and their families have a number of important decisions to make about this phase of the illness. The first concerns End Of Life Issues
where the patient will be cared for. Some people wish to spend their last monthsat home, and receive terminal care in this setting, but others require the serv- In-home versus outside care ices of a long-term care facility for the final phase of their illness. This may Gastrostomy tube feeding make the patient more comfortable and relieve stress on the family. Patients Life sustaining emergency and their families must decide which treatments they want if they become measures (e.g. CPR, intubation) acutely ill, such as antibiotics for pneumonia, or CPR for a cardiac arrest.
Use of antibiotics to treat infec- Patients who are unable to swallow will die if not given food and fluids by other means, but with a gastrostomy tube they may live for years. Improved caloric Other specific care issues (e.g.
intake can increase resistance to infections, improve physical appearance, and treatment of other ongoing health is sometimes associated with a decrease in chorea. Others may not desire such Guardianship, substituted an intervention, depending on their view of the quality of life at that time and consent, and "living wills" their individual spiritual beliefs.
Autopsy/ brain donation for There are different legal mechanisms in every province by which patients can make their wishes known in advance, but it must be stressed thatthere is no substitute for good communication directly between patients, theirfamilies, and their doctors. The process should start early, so that difficult topics can be introduced gradually, in an unhurried manner, and so that the conversation can take placewhile the patient retains the ability to communicate.
It is also important to readdress these issues periodically. An advance directive reflects a person's ideas at one discreet interval, often several years in the past. For example a blanket statement such as "Iwould never want a feeding tube," made shortly after the diagnosis of HD, may be revised as the patient andfamily gradually adapt to increasing disability.
One must avoid overgeneralizations about "end-stage HD." An intervention that is right for one person may not be right for another. For example, many patients who can no longer eat safely are still able totalk and are fully aware of their surroundings. In one instance a man was told that placement of a gastros-tomy tube would reduce the number of aspiration pneumonias from which he suffered. He replied thateating was one of his few pleasures and he preferred to take this risk, knowing that it might shorten his life.
In another instance, a teenaged girl with juvenile onset HD had become very rigid and was unable to eat. Award of the state, she was initially denied a gastrostomy tube by her official guardian who believed that suchinterventions were "futile" and "only prolong suffering." This decision was reversed when her foster motherstrenuously pointed out that the girl was in no pain, was enjoying activities and family life, could still talk,and in fact had been asking for the tube all along. For other individuals, the issue of a gastrostomy tube doesnot arise until the patient no longer seems aware of his surroundings. In this circumstance, it often seemsbest to a family not to prolong the process artificially, but to support the patient's comfort and let him die anatural death.
It is our hope that when death does come to a person with HD, that this person's family will con- sider making a gift of brain tissue to one of the projects that study such material, which are listed in Appen-dix 1. We hope that, where possible, patients and families will discuss this decision with each other inadvance and will also inform the staff of long-term care facilities and hospices of their intentions ahead oftime. The cost of autopsy and transportation to and from the funeral home are usually born by the institu-tion receiving the donation, and the brain can be removed quickly so as not to delay burial and in such away that it does not show and will not interfere with viewing. These generous gifts, made at a sad time, maygive the person's death great meaning. Each one moves us closer to the day when no one will have to diefrom Huntington disease.
Appendix 1 VOLUNTARY AGENCIES Huntington Society of Canada tel: 1 800 998-7398 151 Frederick Street fax: (519) 749-8965 email: firstname.lastname@example.org Kitchener, Ontario web site: www.hsc-ca.org Huntington Society of Quebec tel: (514) 282-4272 505, boul. de Maisonneuve Ouest, fax: (514) 282-4242 email: email@example.com Montreal, Québec web site: www.hsc-ca.org Huntington's Disease Society of America tel: 1 800 345-4372 158 West 29th Street, 7th Floor fax: (212) 239-3430 New York, New York email: firstname.lastname@example.org web site: www.hdsa.org International Huntington Association tel: +31 573-431595 fax: +31 573-431719 web site: www.huntington-assoc.com BRAIN TISSUE BANK Canadian Brain Tissue Bank tel: (416) 978-7950 Toronto Western Hospital—Western Division fax: (416) 978-7935 Bathurst Wing 4-69399 Bathurst StreetToronto, OntarioM5T 2S8 Canadian Centre for Molecular Medicine and Therapeutics tel: (604) 875-3535 University of British Columbia fax: (604) 875-3819 950 West 28th Avenue, Room 3024Vancouver, BCV5Z 4H4 Appendix 2 PREDICTIVE TESTING CLINICS Predictive testing clinics perform the genetic test for HD and offer genetic counselling. Before testing, agenetic counsellor helps the individual explore reasons for taking the test, and prepare for receiving theresults. After testing, counselling is geared to offering support and assistance in understanding the impact ofeither negative or positive test results on the individual and the family.
Dr. John Stephen Bamforth Dr. Oksana Suchowersky University of Alberta Hospitals Division of Medical Genetics Clinical Sciences Building Alberta Children's Hospital 4th Floor, Room 117 1820 Richmond Road SW 8440 - 112th Street Calgary, AB T2T 5C7 Edmonton, AB T6G 287 Co-ordinator: Linda MacLaren Tel: (403) 492-4077 Tel: (403) 229-7371 Fax: (403) 492-6845 Fax: (403) 229-7624 BRITISH COLUMBIA Dr. Michael R Hayden Dr. Patrick MacLeod Department of Medical Genetics University of British Columbia Victoria General Hospital RM F168-2211 Wesbrook Mall Vancouver, BC V6T 2B6 Victoria, BC V8Z 6R5 Co-ordinator: Elisabeth AlmqvistTel: (604) 822-7738 Tel: (250) 727-4461 Fax: (604) 822-7970 Fax: (250) 727-4295 WinnipegDr. Cheryl GreenbergDepartment of PaediatricsRoom 231 - Children's Hospital685 William AvenueWinnipeg, MB R3E 0W1 Tel: (204) 787-2499Fax: (204) 787-1419 St. John'sNewfoundland & LabradorMedical Genetics ProgramJaneway Child Health CentreJaneway PlaceSt. John's, NF A1A 1R8 Co-ordinator: Marian Crowley / David McGregorTel: (709) 778-4363Fax: (709) 778-4190 NOVA SCOTIA / NEW BRUNSWICK / PRINCE EDWARD ISLAND HalifaxDr. J.P. WelchAtlantic Research Centre – Medical GeneticsIWK Grace Health Centre5850/5980 University AveHalifax, NS B3J 3G9 Co-ordinator: Heather HoggTel: (902) 428-8754Fax: (902) 428-8709 Dr. Mohamed Khalifa Department of Paediatrics & Human Genetics Division of Medical Genetics McMaster University Medical Centre Department of Paediatrics 1200 Main Street West Queen's University Hamilton, ON L8N 3Z5 Co-ordinator: Debbie Eisenberg Kingston, ON K7L 3N6 Tel: (905) 521-5085 Co-ordinator: Ruth Lokkesmoe Fax: (905) 521-2651 Tel: (613) 545-6310Fax: (613) 548-1348 Dr. Hubert Soltan Regional Medical Genetics Centre Children's Hospital of Western Ontario Credit Valley Hospital 800 Commissioners Road East 2200 Eglinton Avenue West London, ON N6A 4G5 Mississauga, ON L5M 2N1 Co-ordinator: Cathy CorleyTel: (519) 685-8140 Tel: (905) 813-4104Fax. (905) 813-4347 Fax: (519) 685-8214 Ms. Francine Robert Kim MacDonald Dr. Wendy Meschino / Anne Summers North Bay & District Health Unit, Genetics Program Clinical Genetics Diagnostic Centre 681 Commercial Street Room 392 - North York General Hospital North Bay, ON P1B 4E7 4001 Leslie Street Tel: (705) 747-1400 North York, ON M2K IEI Fax. (705) 747-8252 Co-ordinator: Andrea ShugarTel: (416) 756-6345Fax: (416) 756-6727 Dr. H. Allen Gardner Dr. Alasdair Hunter / Judith Allenson Director of Genetic Services Division of Genetics Oshawa General Hospital Children's Hospital of Eastern Ontario Oshawa, ON LIG 2B9 Ottawa, Ontario K7H 8L1 Co-ordinator: Maureen Johnstone Co-ordinator: Claire Goldsmith Tel: (905) 576-8711 Tel: (613) 737-2275 Fax: (905) 721-4736 Fax: (613) 738-4822 Sault Sainte Marie Peterborough Country Health Unit Helen Kwolek / Lori Russon 129 - 380 Armour Road Algoma Health Unit Peterborough, ON K9H 7L7 Civic Centre99 Foster DriveSault Sainte Marie, ON P6A 5X6 Tel: (705) 759-5281 x353Fax: (705) 759-1534 SudburyMs. Heather Hare, BSc / Valerie Allison, RN / DoloresFortier, RNGenetic Counselling Services Ms. Cathy Gillies / Linda Spooner / Jan Swain Sudbury, ON P3E IX7 Genetic Counselling Services Tel: (705) 675-4786 Thunder Bay District Health Unit Fax: (705) 675-7911 999 Balmoral StreetThunder Bay, ON P7C 4X8 Tel: (807) 625-5900 Fax: (807) 623-2369 Ms. Michelle Caron-Heroux / Guylaine Malette-RobichaudPorcupine Health UnitGenetics DepartmentBag 2012 - 169 Pine Street SouthTimmins, ON P4N 8B7Tel: (705) 267-1181 x364Fax: (705) 264-3980 Mme Claude Provost Dr. David Rosenblatt Genetic Counsellor Division of Medical Genetics Hôpital de Chicoutimi Department of Medicine McGill University Chicoutimi, PQ G7H 5H6 Tel: (418) 541-1000 x22153 Montreal, PQ H3G 1A4 Fax: (418) 541-1138 Co-ordinator: Suzanne DufrasneTel: (514) 937-6412Fax: (514) 934-8273Co-ordinator: Lidia KasprzakTel: (514) 843-1449Pager: (514) 988-6700Fax: (514) 934-8273 SaskatoonDr. Eli LemireDepartment of Medical GeneticsRoyal University HospitalRoom 515, Ellis HallUniversity of SaskatchewanSaskatoon, SK S7N OXO Co-ordinator: Sharon CardwellTel: (306) 655-1692Fax: (306) 655-1736 This list of predictive genetic testing centres is maintained for information purposes only. Inclusion in the list does not constitute an endorsement or recommendation by the Huntington Society of Canada.
Appendix 3 REHABILITATIVE/ADAPTIVE EQUIPMENT ANDPRODUCT INFORMATION Kirton Healthcare 72 Victoria Street South Kitchener, Ontario N2G 2A9 Haverhill, Suffolk CB9 8PB (800) 668-0637 (Canada and US) Specialized HD chairs Halesworth chair Furnco Healthcare, Inc.
Lazy Boy Recliners Local Lazy Boy furniture dealer Orillia, Ontario L3V 6K8 Luxury lift power recliners (705) 329-2711Q-foam chairs, walkers, and miscellaneous adaptive equipment 250 Prairie Center Drive, Suite 211Minneapolis, MN 55344 Gunnel, Inc.
8440 State Street Millington, MI 48746 Posture Guard (wheelchair with body guard); cus- (800) 551-0055Gunnel Custom Recliner; customized wheelchairs PDG, MedBloc700 Ensminger Road, U112 Tonawanda, NY 14150 1069 State Bank 46 East Batesville, TN 47006 Bentley Chair (800) 445-3730Customized wheelchairs Piccard Medical Corp.
1032 Stuyvesant Avenue Weyerhauser, WI 54895 1 (800) 4SCRIPTCustomized wheelchairs BEDDING, PADDING, LOW BEDS, BED ENCLOSURES 4477 Harlen Street Wheat Ridge, CO 80033 Bed padding Bed enclosure NOA Medical Industries St. Louis, MO 33114 Bed enclosure Profex Bumper PadsPO Box 160438013 Maryland Ave.
St. Louis, MO 63105(800) 325-0196Foam products; adaptive equipment WALKING DEVICES Guardian Products 12800 Wentworth Street 4175 Guardian Street Simi Valley, CA 93063 Walkers; adaptive equipment Grandtour walking device, rolling walker, standardwalker, canes, adaptive equipment Sammons PrestonPO Box 5071Bolingbrook, IL 60440(800) 323-5547Strider walker, standard walker; adaptive equipment REHABILITATION AIDS AND SAFETY PRODUCTS Access to Recreation J.T. Posey Co.
2509 East Thousand Oaks Blvd., Suite 430 Thousand Oaks, CA 91362 Arcadia, CA 91006 Adaptive equipment for recreation and activities of Positioning devices; adaptive equipment daily living 29 Wells Ave.
Yonkers, NY 10701 Positioning devices; safety products Smith & Nephew Rolyan North Coast Medical N93 W14475 Whittaker Way 2509 E. Thousand Oaks Blvd., Suite 430 Menomonee Falls, WI 53051 Thousand Oaks, CA 91362 Padding materials; adaptive equipment FOOD PREPARATIONS FOOD THICKENERS: Diafoods Thick-It Food Thickener Milani Foods, Inc.
2325 Armitage Ave.
210A Denison Street Melrose, IL 60160 Markham, Ontario L3R 1B6 (708) 450-3189 and toll-free (800) 333-0003 Thick ‘N Easy Instant Food ThickenerAmerican Institutional Products, Inc.
PO Box 5387Lancaster, PA 17601 FOOD MOULDS: The Thick 'N Easy Recipe Book Culinary Purée, Inc.
American Institutional Products, Inc.
6001 Felstead Road Evansville, Indiana Lancaster, PA 17601 477121 800 981-7744 Blending MagicBernard Jensen ProdcutsPO Box 8 INFORMATION AND SUPPLIES 124 East Cliff Street FOR PURÉED FOODS: Solana Beach, CA 92075 Non-Chew Cookbook 198 Mammoth Road #4 J. Randi Wilson, 1985 Appendix 4 The following rehabilitation survey, developed by Lori Quinn, Ed.D., P.T., New York Medical College, may behelpful in assessing a patient's ability to perform activities of daily living (ADL), either in the home or in along-term care setting, and also in recommending adaptive equipment where necessary.
SAMPLE REHABILITATION SURVEYHUNTINGTON DISEASE PROGRAM Indicate amount of caregiver assistance, current equipment used, and safety or other concerns involved foreach ADL activity. Place a check (✔) next to the recommended equipment and list specific instructions orrecommendations on provided lines.
q Pull over shirts q Ring zipper pull Shoes (Donning/Doffing) _ q Supportive sneakers q Elastic shoelaces q Long handled shoehorn q Referral to orthotics clinic (heel lift, molded inserts) q Extra long mitts q Milk carton holder q Keep most used items at waist level or below Eating/Drinking _ q Straw (one-way) q Weighted spoon/fork q Cup with lid and straw q Non stick dycem q Inner lip plate q Rolling/standard walker q Rollator (3 or 4 wheels) q Cane (straight) q Sit in supportive chair with sturdy seat and back when eating, drinking, q Horizon or Broda chair, tilt-in-space with maximal padding _ q Self propelling wheelchair Environmental adaptations (layout of room, padding on furniture, rugs, etc.) Other Recommendations q Ankle/wrist weights _Signature, Title Appendix 5 SAMPLE DISABILITY LETTER The following is intended as a guide to the areas that typically should be addressed in a disability application,whether the physician is completing a standard form or writing a generalized letter. Not all sections will apply toevery individual with HD.
Adapted from the Baltimore Huntington's Disease Center at The John Hopkins Hospital, Baltimore, MD. This report is to provide medical support for the disability application of who hasHuntington disease (HD).
Mr./Mrs./Ms. was seen in our clinic for the first time on , and clinicallydiagnosed as affected with Huntington disease on . Symptoms began in . Wehave followed him/her yearly since , and are confident of the diagnosis based upon clinicalobservations, his/her positive family history of an affected , and DNA CAG tripletrepeat expansions which confirm that he/she has the mutation that causes Huntington disease.
HD is an inherited neuropsychiatric disorder that is progressive and terminates in death of the affectedperson. Recovery or remission never occur. Diagnosis is based upon clinical symptoms, a positive familyhistory, and DNA testing. An MRI done on reports " ." Autopsy of thebrain following death will provide further confirmation of the clinical diagnosis.
Treatment is ineffective in terms of progression of the disease. Incapacitation occurs relatively early in thecourse of this debilitating illness with progression to total disability and dependency for all activities of dailyliving. There are 3 characteristic clinical features: 1) loss of ability to control bodily movements, 2) loss ofability to think and act quickly, to learn new material and to remember, and 3) apathy and severe depression,often resulting in suicidal behaviour. Patients also exhibit poor social judgement and may be irritable andaggressive.
When last examined on , Mr./Mrs./Ms. _ had abnormal eye movements, slow/dysarthricspeech, poorly coordinated finger-thumb tapping, and rapid alternating movements.
He/she has increased risk for falling secondary to his/her impaired voluntary movements and his/her signifi-cant chorea as well as his/her disrupted gait. The Activities of Daily Living Examination revealed that thepatient is slow and clumsy, and has begun to spill things and drop objects. Because of his/her HD, thepatient cannot learn new information which makes job training and rehabilitation more difficult. Apathyand severe chorea have resulted in more time spent in sedentary activities. If left alone, he/she does noth-ing. Unless medications are distributed or monitored by a caretaker, he/she frequently forgets to take them.
He/she is no longer capable of preparing meals without help, keeping up with home maintenance or repairs,or making rational decisions about spending. Although he/she lives alone/with spouse, he/she experiencesincreased difficulty getting through the simplest of tasks.
He/she has great difficulty initiating and completing projects. He/she is tired and lethargic as a result of thedisease, and his/her concentration and attention are grossly diminished. He/she also finds it very difficult tothink through problems.
As for the sensory examination, Romberg and cranial nerves are not affected in Huntington disease.
Mr./Mrs./Ms. _ last worked on . His/her difficulties on the jobwere first noted in . At that time, he/she . Although his/her intelligence isjudged to be (low average/average/high average) , his/her insight is grossly impaired.
Mr./Mrs./Ms. has/has not suffered from depression associated with HD since _. Depression is usually quite common in this population. This disorder has/has not beentreated successfully with since . Although the treatment has providedsome symptomatic relief, it has not improved the patient's ability to function. The progression of his/herneurological and cognitive decline will worsen without remission for the duration of his/her life.
He/she is not a candidate for vocational training now, or at any time in the future because, like all patientswith HD, he/she has progressive cognitive and neurological degeneration and is unable to learn new tasks.
Neurologically, fine and gross motor task performance is unsafe and ultimately impossible due to poor motorcoordination. These patients are at high risk for accidents, especially in manual labor jobs, as a result of thisneurological deterioration.
In summary, this _ year old male/female was well until when HD began. He/she has beenunable to work since _ because of the motor impairment, cognitive inefficiency and psychiatricfeatures mentioned above. We hope you will grant disability to this fatally ill individual. If you wish furtherinformation, please call _.
References andAdditional Reading 1. Brandt, J. and Butters, N. 1996. Neuropsychological characteristics of Huntington disease, in I. Grant (Ed). Neuropsychological assessment of neuropsychiatric disorders. 2nd edition, Oxford University Press:New York.
2. Folstein M.F., Folstein S.E., McHugh P.R. 1975. "Mini-Mental State": A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res, 2:189-198.
3. Folstein, S.E. 1989. Huntington's Disease: A Disorder of Families. The Johns Hopkins University Press: 4. Folstein S.E., Jensen B., Leigh R.J., Folstein M.F. 1983. The measurement of abnormal movement: Meth- ods developed for Huntington disease. Neurobehav Toxicol and Teratol, 5:605-609.
5. Harper, P.S. 1996. Huntington's Disease, 2nd Edition. WB Saunders: London.
6. Huntington Study Group. 1996. Unified Huntington disease rating scale: Reliability and consistency.
Movement Disorders, 11:136-142.
7. MacDonald, M.E. and Gusella, J.F. 1996. Huntington disease: translating a CAG repeat into a pathogenic mechanism. Current Opinion in Neurobiology, 6:638-643.
8. Matiss, S. 1988. Dementia Rating Scale (manual). Psychological Assessment Resources: Odessa, FL.
9. Nance, Martha A. 1996. Huntington Disease - Another Chapter Rewritten. American Journal of Human 10. Paulsen, J.S. 1999. Understanding Behaviour in Huntington Disease. Huntington Society of Canada.
11. Ross, C.A. 1997. Intranuclear neuronal inclusions: A common pathogenic mechanism for glutamine- repeat neurodegenerative diseases? Neuron, 19: 1147-1150.
12. Ross, C.A., Margolis, R.L., Rosenblatt, A., Ranen, N.G., Becher, M.W., and Aylward, E.A. Reviews in molecular medicine: Huntington disease and a related disorder, dentatorubral-padoluysian atrophy(DRPLA). Medicine, 76:305-338.
13. Rubinsztein, D.C. and Hayden, M.R. 1998. Analysis of Triplet Repeat Disorders. Bios Scientific Pub- lishers: Oxford.
14. Wells, Robert D., Warren, Stephen T., Sarmiento, M., Eds. 1998. Genetic Instabilities and Hereditary Neurological Diseases. Academic Press: San Diego.
Huntington Society of Canada 151 Frederick St., Suite 400 Kitchener, Ontario N1R 7G6 Tel: (519) 749-7063 Fax: (519) 749-8965 Toll free in Canada: 1-800-998-7398 Email: email@example.com Web site: www.hsc-ca.org
2nd International Conference on Multidisciplinary Research & Practice P a g e 182 Purification of Chlorzoxazone by Adsorption A Bharucha1*, V Patel1, C Patel1, C Prajapati1, A Parmar1, V Desai1, A Sharma1 1Chemical Engineering Department, Sarvajanik College of Engineering and Technology, Surat, Gujarat Abstract: Chlorzoxazone (C7H4ClNO2) chemically 2-hydroxy