Huntington’s Disease
Date: Monday, May 17 @ 04:06:23 IST
Topic: Medicine
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This topic was recently asked in AIIMS May 2004 Paper, so we present it as an contentious topic here.
Summary
Degenerative neuropsychiatric disorder
Slowly progressive cognitive, emotional, and motor decline
90% insidious mid-life onset (35-50 years); 10% juvenile onset (<20 years)
Prevalence 1/10,000
Affects all races and ethnic groups
Affects both sexes
Mode of Inheritance: Autosomal Dominant (from parent to child)
50% chance of inheriting from gene-carrying parent
Greater chance of earlier onset when inheriting from father
Diagnosis is based on:
History of relative with typical motor signs of HD
Presence of chorea and/or motor impersistence on exam
Huntington’s Disease Psychiatric symptoms
HD supposedly can cause psychiatric disorders in 2 ways
Direct action of the gene on striatal neurons
Indirect effect of the disordered family environment on the children regardless of whether they inherited the HD gene.
Huntington’s Disease Psychiatric symptoms
Symptoms range from personality alterations to mood disorders, aggressiveness, hyper sexuality or impotence, alcoholism, and psychosis, including schizophrenia.
Psychiatric disorders may occur in 35-73% of patients with HD, and behavioural changes may represent the initial manifestation of the disease in one third to one half of the cases.
Huntington’s Disease Psychiatric symptoms
Depression is the most common psychiatric condition.
Mania occurs in 2-12% of patients, whereas suicide occurs in nearly 6% of patients.
Eccentricity, inappropriateness, loss of social amenities, excess irritability, and sexual hyperactivity can mark the early stages.
Occasionally, a schizophreniform illness precedes the motor abnormality by several years.
Depression, apathy, social withdrawal, and intermittent disinhibition are common.
Suicide occurs frequently, partially because the progressing dementia often fails to blunt insight.
Huntington’s Disease Presentaion
When HD starts as subtle fidgeting, it may be unrecognized by the patient and family. A history of progressive generalized choreiform activity accompanied by behavioural or personality changes exists, especially in patients with a family history. Sporadic cases also are possible.
Huntington’s Disease Cognitive symptoms
Memory frequently is not impaired until late in the disease, but attention, judgment, and executive functions may be seriously deficient at an early stage.
Early signs of dementia often are forgetfulness, disorganization, and affective disorders.
Free recall may be severely impaired.
Memory deficits involve both recent and remote function.
Huntington’s Disease Cognitive symptoms
Significant problems with frontal executive functions exist, such as problems with maintenance, cognitive flexibility, abstraction, judgment, reasoning, sequencing, organizing, planning, and adapting.
Skilled motor-procedural learning deficits are reported. Working memory may be affected in patients with HD because of frontal lobe dysfunction associated with the bidirectional connections with the caudate.
Insight, orientation, factual information, and overall intelligence quotient scores are preserved relatively well into the disease process.
Huntington’s Disease Verbal skills
Verbal skills are least impaired in patients with HD.
Reduced fluency in the face of preserved confrontation naming occurs.
Letter and category fluency also are impaired.
Sensory motor deficits occur, such as poor olfactory perception, slow sequential or graphomotor movements, and impaired prism adaptation.
Huntington’s Disease Differential Diagnosis
Genetic disorders Dentatorubropallidoluysian (DRPLA) Neuroacanthocytosis Wilson disease Hereditary ataxias Benign hereditary ataxia Mitochondrial disorders.
Gilles de la Tourette syndrome
Chorea Senile Chorea Reversible adult chorea -lupus erythematosus -thyrotoxicosis
Huntington’s Disease Disorders that may mimic HD
Schizophrenia
Benign familial chorea
Inherited ataxias
Neural acanthocytosis
Familial Alzheimer disease
Other conditions with dementia Parkinson disease (PD) Supranuclear palsy Dementia of the frontal lobe
Pick disease
Huntington’s Disease Investigations
DNA repeat expansion
Dopamine homovanillic acid
Computed tomography or magnetic resonance imaging
Single-photon emission computed tomography scan
Wechsler Memory Scale (Revised)
Wisconsin Card Sorting Test
Trail-Making Test parts A and B
Stroop tests
Huntington’s Disease Histologic Findings
The disease predominantly strikes the striatum.
Gliosis and neuronal loss occur, especially of medium-sized spiny neurons in the caudate and putamen.
Relative sparing of large, cholinergic, aspiny neurons occurs.
Huntington’s Disease Investigations
In summary, patients with HD are most deficient on tests of delayed recall, followed by performance on measures of memory acquisition, cognitive flexibility and abstraction, manual dexterity, attention and/or concentration, performance skills, and verbal skills.
Huntington’s Disease Medical Care
Acetylcholinesterase inhibitors (eg, rivastigmine, memantine) may have positive effects on cognition, though no treatment halts the progression of this illness.
Huntington’s Disease Symptomatic care
Aimed at minimizing the distressing movements.
Pharmacological intervention is available for the behaviour and/or psychologic disturbances, chorea, and weight loss.
Treatment for patients with depression is used to improve mood, functional status, and quality of life.
Huntington’s Disease Cognitive care
Patients who are cognitively impaired require a multidisciplinary treatment approach, which must be based on a solid alliance with the patient and family.
Ongoing assessment should include periodic monitoring of the development and evolution of cognitive and non-cognitive psychiatric symptoms and their response to intervention.
Safety measures include evaluation of suicidal tendency and the potential for violence; recommendations regarding providing adequate supervision, preventing falls, and limiting the hazards of wandering; vigilance regarding neglect or abuse; and restrictions on driving and the use of other dangerous equipment.
Also, helping patients and their families plan for financial and legal issues is important.
Huntington’s Disease Psychosis care
Intervention should be guided by the patient's level of distress and risk to the patient or caregivers.
In addition to distress, if agitation, combativeness, or violent behaviour causing danger to the patient or others occurs, psychopharmacologic treatment is indicated.
Huntington’s Disease Surgical Care (experimental)
Neural transplantation Fetal human striatal implants to replace lost neurons and/or prevent the degeneration of neurons destined to die most likely will be the first transplant strategy attempted in clinical trials.
Human fetal striatal tissue grafts A study conducted in France examined whether grafts of human fetal striatal tissue could survive and have detectable effects in 5 patients with mild-to-moderate HD. Fetal neural allografts could be associated with functional, motor, and cognitive improvements in patients with HD.
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