Definition:

Autosomal dominant progressive neurodegenerative disorder characterized by movement disorders, psychiatric symptoms and cognitive decline including dementia.

 

Etiology:

Genetic disorder inherited in an autosomal dominant (AD) manner due to expansion of the cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin (HTT) gene (or HD or IT15 gene) and is located on chromosome 4.

The number of repeats with in the genes correlates with the age of onset; meaning expanded repeats at earlier age of onset would occur in greater numbers when compared with later age onset disease.

 

• Children of an affected parent with Huntington's disease have ~50% risk of developing the condition
• Abnormal expansion of the CAG triplet repeat within the HTT gene results in abnormal processing of the corresponding Huntingtin protein, which gradually leads to neuronal damage within the basal ganglia
• Large CAG expansions produce more widespread injury in the neurons

 

Epidemiology:

• Prevalence: 1 in every 10,000 in Canada
• Juvenile Huntington's (Westphal variant) occurs in approximately 16% of all cases
• No gender or ethnic predominance
• Mean age of onset is 35 to 44 years
• 25% present after 50 years
• Apparent lack of positive family history (e.g. non-paternity) may delay diagnosis

 

Pathophysiology:

• Under normal conditions Huntingtin protein is present throughout the brain, and within a large number of tissues throughout the body
• Mutant Huntingtin gene with CAG expansion leads to transcription and expression of abnormal Huntingtin protein
• Selective neuronal loss within the caudate and putamen underlies the development of Huntington's symptoms
• Thus despite widespread presence of abnormal huntingtin protein, selective neuronal vulnerability results in a specific pattern of cell loss and the clinical features of the disease
• The abnormal huntingtin protein is cleaved into smaller, toxic fragments that bind together and accumulate within neurons, disrupting the normal functions of these cells, including impaired axonal transport and synaptic transmission.Other potential mechanisms of neuronal cells death includes:
  • Increased oxidative stress
  • Mitochondrial dysfunction
  • Activation of proteases → leading to proteolysis
  • Apoptosis

 

Clinical Presentation:

 

The clinical features can be divided into motor, cognitive and psychiatric deficits. Among these chorea (abnormal involuntary movements), intellectual decline and emotional disturbances are most prominent.

 

• Clinical features of HD

 

The presentation is divided into early, middle and late stage.

 

• Clinical stages of HD

 

Investigation and Workup:

Diagnosis is assisted by:

➣ Clinical presentation

➣ Positive family history

➣ Genetic testing for CAG expansion in huntingtin gene

 

Imaging:

• CT/ MRI brain

 

Genetic testing:

• Targeted mutation analysis:
  • PCR-based methods detect alleles up to about 115 CAG repeats
• Southern blot analysis:
  • Identification of large expansions which may fail to amplify well by PCR analysis associated with juvenile-onset HD
  • Confirmation of apparent homozygous genotypes obtained by PCR analysis

 

Interpretation of genetic testing for CAG repeats

 

 

Genetic counseling:

All patients or family members should be offered genetic counseling, but not all patients may want or need genetic testing.

 

Issues to be addressed are as follows:

Inheritance pattern:

• Each child of an affected individual has a 50% chance of inheriting the abnormal huntingtin gene
• Inheriting a normal huntingtin gene from the unaffected parent does not prevent or counteract the disease-causing effects of the abnormal gene
• Greater expansion with paternal inheritance

 

Absent family history of HD:

• ~2-5% of all cases develop HD without knowing that they were at risk
• parent carrying a gene did not live long enough to manifest the symptoms)
• Non-paternity

 

Usefulness of genetic testing:

• Diagnostic or confirmatory testing - (if the clinical suspicion is strong then it is the only diagnostic test needed)

 

• Predictive or presymptomatic testing** (recommended in an individuals with no symptoms, but wishes to know if he carries the expanded gene). Current implications are that no cure or treatment to slow down disease progression currently exists

 

** May pose potential psychosocial risks and hence often

requires different clinical approach with appropriate

counseling.

 

• Prenatal testing: Prenatal testing for HD is possible, and should be performed in conjunction with detailed genetic counseling

 

Treatment Goals:

• Symptomatic improvement
• Minimize complications associated with disease progression
• Maintain functionality as long as possible
• Improve the patient's overall quality of life

 

Therapeutic Choices:

To date, HD is a universally a fatal disease. Several studies have investigated potential neuroprotective therapies and many are still ongoing. However, none of the trials have shown any proven benefit.

 

Treatment for HD is largely symptomatic and highly individualized to help control physical and mental deficits.

 

Treatment strategies vary over time and from individual to individual, even within a family.

 

Always consider non-pharmacological interventions first.

 

TREATMENT STRATEGY:

• Non-pharmacological
• Pharmacological

 

Non-pharmacological therapy:

Can be used to assist physical disabilities and mental conditions and includes:

 

• Physiotherapy: Improve/maintain posture, strength, coordination, balance, gait

 

• Occupational therapy: Assess for safety and need for assistive devices. Improve ambulation, avoid falls, and improve nutrition (eating)

 

• Speech therapy: Improve/maintain speech and swallowing

 

• Dietitian: To ensure adequate nutrition

 

• Psychological therapy: Counsel patient and family members; assist in coping with skills

 

• Social work support: Help family prepare for deteriorating clinical course
  • Assist with arrangements for (full time) supervision as required
  • Suggest and assist with identification of alternate living arrangements (assisted living, nursing home) if required

 

Pharmacological therapy:

To date, the only FDA recommended drug for use in HD is tetrabenazine to treat chorea. There is currently a lack of evidence-based medicine recommendations due to few class I, randomized controlled trials (RCTs) of agents for any of the symptoms and thus no treatment guidelines exist.

 

The current choice of agents for any of the motor, psychiatric and cognitive symptoms relies on expert opinion, physicians' personal choice and knowledge of an agent balanced against potential side-effect profile.

 

For convenience; therapy is documented according to symptoms during the disease course.

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Medications for physical symptoms:

 

Chorea: A prominent movement disorder of HD which changes overtime, eventually peaks and then begins to decline. Treatment is initiated when chorea begins to interfere with voluntary activities like writing, cooking, eating or causes injury due to fall or accidents. It is worsened by stress, anxiety, depression and lack of sleep. Not all patients require treatment and the need has to be balanced against side-effects.

 

(a) Monoamine depleting agents:

• Tetrabenazine: 25 mg/day PO daily; may increase to TID

 

(b) Dopamine D2 antagonists:

May treat both chorea and some psychiatric symptoms.

 

Typical antipsychotics:

 

• Haloperidol: Start at low dose 0.5-1 mg PO 1 or 2 divided doses, with gradual increase
• Fluphenazine: Start at low dose 0.5-1 mg PO 1 or 2 divided doses, with gradual increase
• Thiothixene hydrochloride: Start with1-2 mg/day PO in 1 or 2 divided doses
• Thioridazine: 10 mg/day PO in 1 or 2 divided doses

 

Atypical antipsychotics:

 

• Risperidone: 0.5-1 mg/day PO in 1 or 2 divided doses
• Olanzapine: 2.5-5 mg/day PO daily
• Aripiprazole: 10-15 mg/day PO daily
• Quetiapine: 25-50 mg/day PO daily

 

(c) Amantadine - may be helpful for mild chorea

 

(d) Benzodiazepines - see below

 

Dystonia, rigidity, Parkinsonism and spasticity:

With disease progression the clinical phenotype changes from hyperkinetic to hypokinetic. Thus dystonia may become more evident with more sustained muscle contractions. Rigidity and parkinsonism is also evident with advanced disease. In Juvenile onset (due to the larger number of CAG repeats); this hypokinetic phenotype is often the presenting feature with parkinsonism, plus spasticity and cerebellar ataxia.

 

(a) Benzodiazepines:

• Clonazepam:
  • Dose in chorea: 0.5-5 mg/day PO
  • Dose in spasticity and stiffness: 10 mg/day PO increasing up to 60 mg/day in divided doses
• Diazepam:
  • For Chorea: 1.25 mg/day in divided doses up to 10 g /day
• Lorazepam: 1-6 mg PO daily in divided doses

 

(b) Antispasmodic:

• Baclofen: 10-60 mg PO daily in divided doses

 

(c) Alpha 2-adrenergic agonist:

• Tizanidine: 2 mg PO daily, increasing every weekly up to 12-24 mg,for spasticity with or without baclofen

 

(d) Antiparkinson drugs:

May also be used (cautiously) to relieve spasticity, rigidity, dystonia and includes

• Levodopa/carbidopa: 100/25 mg two to three times per day

 

(e) Botox: For focal dystonia

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Medications for psychiatric and cognitive symptoms:

 

Depression:

 

(a) Tricyclic antidepressants (TCA):

• Nortriptyline: 10-25 mg PO daily, up to 150-200 mg daily

 

(b) Selective serotonin reuptake inhibitors (SSRI):

• Fluoxetine: 10-20 mg PO daily up to 60-80 mg
• Sertraline: 25-50 mg PO daily, up to the max of 200 mg
• Paroxetine: 10-20 mg PO daily, up to 40-60 mg

 

(c) Selective norepinephrine reuptake inhibitors

(SNRI):

 

• Venlafaxine: Start 25-37.5 mg PO; may increase up to 225 mg/day in divided doses or once daily (XR)

 

(d) Others:

• Buproprion: 100-200 mg PO daily in divide doses, max dose 300-450 mg

 

Dementia:

No specific treatment. Cholinesterase inhibitors (donepezil, rivastigmine and galantamine) have been tried, but no proven benefit.

 

Violent outbursts/agitation:

 

(a) Benzodiazepines:

Short acting drugs such as lorazepam may be another good choice, for the short-term management of agitation

• Lorazepam: 1-2 mg/day PO at bedtime or 2-3 times a day

 

(b) Neuroleptics/antipsychotics (as above)

 

Mood stabilizers/mania:

• Valproic acid: 125-250 mg PO BID; increase dose gradually to effective level or reach a serum concentration of 50-120 mcg/mL or in SI units (400-700 Umol/L); Max. 500-2000 mg PO BID

 

• Carbamazepine: 100-200 mg PO daily increase gradually by 100 mg/day as tolerated to ~1200-1600 mg/day in 2-3 divided doses

 

• Lithium (particularly if features of bipolar): Start 900-2100 mg (15-20 mg/kg/day) in 3 divided doses - adjust dose to target levels range from 0.8-1.2 mmol/L, as needed and tolerated

 

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MEDICATIONS:

Antipsychotic agent, Typical

• ➣ Fluphenazine
• ➣ Haloperidol
• ➣ Thiothixene

 

Potential Mechanism(s):

• Blocks postsynaptic dopaminergic receptors in the brain
• Depresses the release of hypothalamic and hypophyseal hormones
• Also have weak anticholinergic activity and antiemetic effect

 

Doses:

Fluphenazine

Psychosis:

• Start 0.5-2.5 mg PO and increase to 2.5-10 mg/day in divided dose at 6-8 hrs interval; usual maintenance dose 1-5 mg once daily; Max. 20-30 mg/day

 

Chorea:

• Start 0.5-1 mg/day PO; Max. 6-8 mg/day

 

Haloperidol

Psychosis:

• Start 0.5-2.5 mg PO and increase to 0.5-5 mg PO BID-TID; maximum usual dose: 20-30 mg/day

 

Chorea:

• Start 0.5-1 mg/day PO; Max. 6-8 mg/day

 

Thioridazine

Psychosis:

• 10 mg/day PO in 1 or 2 divided doses

 

Chorea:

• Start 10 mg/day PO in divided doses; max dose 100 mg/day

 

Thiothixene

Mild-to-moderate psychosis:

• Start: 5 mg PO BID, increase gradually up to 20-30 mg/day as required: Max 60 mg/day

 

Rapid tranquilization of the agitated patient

(administered every 30-60 minutes):

 

• 5-10 mg PO; average total dose for tranquilization: 15-30 mg

 

Chorea: 1-2 mg/day PO; max dose upto 10-20 mg/day

 

Antipsychotic agent, Atypical

• ➣ Aripiprazole
• ➣ Olanzapine
• ➣ Risperidone
• ➣ Quetiapine

 

Potential Mechanism(s):

• Exact mechanism(s) of action is unknown
• Potent antagonist of serotonin 5-HT_2a, dopamine D₂, receptors
• Potentially blocks dopamine transmission and treat chorea and psychiatric symptoms

 

Doses:

Aripiprazole

Psychosis:

• 10-15 mg PO once daily; if needed, may increase dose gradually to maximum of 30 mg PO once daily at minimum of 2 weeks of interval

 

Olanzapine

Psychosis:

• 2.5-5 mg PO once daily and increase as tolerated 10 mg PO once daily within 5-7 days as required; may increase by 5 mg/day at weekly intervals. Usual maintenance dose 10-20 mg once daily; Max. 15-20 mg/day
• Usual dose in elderly is 1.25-7.5 mg

 

Risperidone

Psychosis/chorea:

• May begin with 0.5-1 mg PO once or twice daily. Increase gradually by 1-2 mg/day on a weekly basis to target dose of 4-8 6 mg/day
• For psychosis may increase as tolerated to max. dose of 4-6 mg/day

 

Quetiapine

Psychosis:

• Start 25 mg PO BID; followed by increments of 25-50 mg daily divided over 2-3 doses, as tolerated to a target dose of 300-400 mg/day in 2-3 divided doses within 4 days (if needed). May increase further by 25-50 mg divided BID every 2-3 days if required; usual maintenance range: 300-800 mg/day

 

• Hepatic impairment: Initialy 25 mg/day, increase dose by 25-50 mg/day to effective dose, based on clinical response and tolerability to patient

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Monoamine depleting agent

• ➣ Tetrabenazine

 

Mechanism:

• Reversibly inhibits uptake of monoamine neurotransmitters in presynaptic vesicles
• Inhibits presynaptic dopamine release and also blocks CNS dopamine receptors
• Also depletes monoamine stores from nerve terminals

 

Doses:

Tetrabenazine

Hyperkinetic movement disorders:

• Start 12.5 mg PO BID or TID; may be increased by 12.5 mg/day every 3-5 days slowly to maximal tolerated and effective dose, if needed; usual maximum tolerated single dose 25 mg PO in poor metabolizers
• Daily dosage >100 mg/day are not recommended
• However, some have reported that doses up to 200 mg/day have been used on rare occasions

 

Benzodiazepines

• ➣ Clonazepam
• ➣ Diazepam
• ➣ Lorazepam

 

Mechanism:

• Benzodiazepines bind to the gamma sub-unit of the GABA receptor and enhance the inhibitory effect of GABA
• Increase the frequency of channel opening events, leads to
  • Increase in chloride ion conductance and inhibition of the action potential
• All benzodiazepines exert five major effects: (i) Anxiolytic (ii) Hypnotic (iii) Muscle relaxant (iv) Anticonvulsant (v) Amnesia (transient loss of memory)

 

Doses:

Clonazepam

Chorea:

• Start 0.5 mg/day PO; may increase to 4 mg/day in divided doses as tolerated

 

Spasticity/ rigidity:

• 10 mg/day PO; may increase up to 60 mg/day as needed and tolerated

 

Diazepam

Chorea:

• 1.25 mg/day in divided doses up to 20 mg/day in divided doses

 

Lorazepam

Chorea:

• 1-6 mg PO daily in divided doses

 

Violent outbursts/ agitation:

• 1-2 mg/day PO at bedtime or 2-3 times a day

 

Antispasmodics

• ➣ Baclofen
• ➣ Tizanidine

 

Mechanism:

Complete mechanism of action unknown.

Baclofen

• It inhibits both monosynaptic and polysynaptic spinal reflexes, possibly by hyperpolarization of afferent terminals (resultant relief of muscle spasticity)

 

Tizanidine

• It is chemically-related to clonidine and other α₂-adrenergic agonists, which acts as a centrally acting muscle relaxant with anti-hypertensive properties
• Presumably it reduces spasticity by increasing presynaptic inhibition of motor neurons

 

Dose:

Baclofen

Spasticity/ rigidity:

• 10 mg/day PO; may increase up to 60 mg/day as needed and tolerated

 

Tizanidine

• 2 mg PO daily at bed time, may increase weekly up to maximum of 12-24 mg/day in divided dose, ( used with or without baclofen)

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Dopaminergic agents

• ➣ Levodopa/ carbidopa

 

Mechanism:

• Act on dopamine receptors in striatum to modulate basal ganglia function

• Carbidopa and B benserazide inhibit peripheral breakdown of Levodopa (L-Dopa) by inhibiting decarboxylation, thereby increasing availability of L-Dopa to cross the blood brain barrier (BBB)
• Within the basal ganglia L-Dopa is then converted to dopamine

 

Dose:

Levodopa/ carbidopa

• 25/100 mg PO two to three times per day

 

Glutamate antagonist

• ➣ Amantadine

 

Mechanism:

Possibly enhances dopamine action by:

• Blocking the reuptake of dopamine into presynaptic neurons
• Increase dopamine release from presynaptic fibers
• Reduces levodopa-induced dyskinesia by antagonism of NMDA glutamate receptors

 

Dose:

• 50-200 mg per day PO

 

Tricyclic antidepressants (TCAs)

• ➣ Nortriptyline

 

Use: Depression

 

Mechanism:

• Inhibits the presynaptic reuptake of neurotransmitters → increases synaptic serotonin and/or norepinephrine → potentiates its effect
• Also has significant anticholinergic properties

 

Dose:

Nortriptyline

• 10-25 mg PO daily; may increase gradually to 150-200 mg if needed

 

Selective serotonin reuptake inhibitors

• ➣ Fluoxetine
• ➣ Paroxetine
• ➣ Sertraline

 

Use: Depression

 

Mechanism:

• Inhibits the presynaptic reuptake of neurotransmitters, in turn increases synaptic serotonin concentration and potentiates its effect
• Little effect on the reuptake of norepinephrine or dopamine
• Does not significantly bind to alpha-adrenergic, histamine, or cholinergic receptors

 

Dose:

Fluoxetine

• Start 10 mg PO; may increase to 20 mg after at least 1 week; Max. 60-80 mg

 

Paroxetine

• 10 mg PO; may increase to 20 mg after at least 1 week, if well tolerated; Max. 40-60 mg

 

Sertraline

• 25-50 mg PO; may increase to 50-100 mg after at least 1 week; Max. 200 mg

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Serotonin/Norepinephrine reuptake inhibitor (SNRI)

• ➣ Venlafaxine
• ➣ Duloxetine
• ➣ Nefazodone

 

Mechanism:

Exact mechanism of action is unknown.

• A potent serotonin and norepinephrine reuptake inhibitor
• Weakly inhibits dopamine reuptake
• Duloxetine has similar affinity to NE and 5-HT receptors (Ki ratio 9) whereas venlafaxine has a relatively higher binding affinity to norepinephrine

 

Dose:

Venlafaxine

• Start 25-37.5 mg PO; may increase up to 225 mg/day

 

Duloxetine

• Start 30 mg PO daily; may increase 30 mg/week up to 120 mg/day

 

Nefazodone

• 50-100 mg 450-600 mg

 

Antidepressant, Dopamine reuptake inhibitor

• ➣ Buproprion

 

Mechanism:

Exact mechanism of action is unknown.

• Binds selectively to the dopamine transporter, but its behavioural effects have often been attributed to its inhibition of norepinephrine reuptake
• Often acts as nicotinic acetylcholine receptor antagonist

 

Dose:

Bupropion

• 100-200 mg PO daily in divide doses, max. dose 300-450 mg

 

Mood stabilizers/Antimanic

• ➣ Valproic acid
• ➣ Carbamazepine
• ➣ Lithium (particularly if features of bipolar)

 

Mechanism:

Carbamazepine

• Blocks voltage-gated sodium channels and may potentiate GABA receptors; decreases synaptic transmission within CNS

 

Valproic acid (valproate)

• Blocks voltage-gated sodium channels and T-type calcium channels. Also affects GABA resulting in decreased synaptic transmission within CNS

 

Lithium

• Alters sodium transport in nerve and muscle cells and Inhibit the intracellular formation of cyclic AMP; enhances serotonin transmission by reducing the activity of post-synaptic serotonin or 5-HT receptors

 

Use: Acute manias/ mood stabilizers

 

Dose:

Carbamazepine

• Start 100-200 mg/day; increase dose gradually by 100 mg/day as tolerated to an effective level or therapeutic level of 5-12 mcg/ml; Max. 1200-1600 mg/day

 

Valproic acid (valproate)

• Start 125-250 mg PO BID; increase dose gradually to effective level or reach a blood level of 50-150 mcg/ml; Max. 1000-2000 mg PO divided BID or TID

 

Lithium

• Start 900-2100 mg (15-20 mg/kg/day) in 3 divided doses - adjust dose to target levels range from 0.8-1.2 mmol/L, as needed and tolerated
• For maintenance therapy, adjust the dose to maintain serum lithium concentrations between 0.6 and 1 mmol/L; once the patient is stabilized than change maintenance dosage to once daily regimen

Renal impairment:

• CrCl 10-50 mL/minute: Administer 50% to 75% of normal dose
• CrCl <10 mL/minute: Administer 25% to 50% of normal dose

 

Clinical Trials:

• The effect of video game-based exercise on dynamic balance and mobility in individuals with Huntington's disease

 

Pipeline Agents:

• Pridopidine for the treatment of motor function in patients with Huntington's disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial

 

Pharmacist Resources:

1. Tips for Patient Care

Encourage:

• Educate patients and caregivers about HD and its treatment
• To get involve more in relaxation techniques
• Restful sleep schedule because sleep disturbance is a common problem in Huntington disease
• >HD patients to do things for him/herself and to participate in primary decision-making as long as possible if it is safe to do so
• Communication in HD patients, if dysarthria is present to promote successful communication, allow enough time to the patient.
• To concentrate on chewing and swallowing by avoiding doing other activities while eating, e.g. avoid talk while eating
• Patients to discuss their ideas about alternate treatments and tell their physicians if they are trying them

 

Drugs:

• Treatment requires integrated, multidisciplinary approach
• Treatment should be individually tailored
• Currently, no treatment can alters, slows, or reverse the progression of HD
• Initially low dose medications are used, whenever possible
• Evaluate cost and affordability and insurance coverage for patients

 

Unlabeled/Alternate uses:

Include, but are not limited to the following:

 

• Haloperidol
  • Nonschizophrenic psychosis
  • Postoperative nausea and vomiting
  • Ethanol dependence (adjunct)
• Risperidone
  • Post-traumatic stress disorder
  • Migraine
  • Post-traumatic stress disorder (PTSD)
• Amitriptyline
  • Neuropathic pain
  • Migraine headaches, prophylaxis
• Fluoxetine
  • Selective mutism
  • Raynaud's phenomenon
  • Fibromyalgia

 

Counseling:

• Genetic counseling is advised if there is a family history of Huntington's disease and also for those couples with a family history of this disease who are considering having children
• Dysphagia and communication difficulties are common problems in HD patients
• Counseling for offspring is also important

 

Alerts:

• Caregiver should monitor periodically for behavioral changes
• Dysphagia is, directly or indirectly, the most common cause of death in people with late stage HD
• In HD patients, falls are common
• Chorea is exacerbated by stress, anxiety, or depression

 

Tips:

• The disease affects everyone differently
• Symptoms may vary from individual to individual, even within a family
• Usually the patient passed the disease to another generation by the time of diagnosis
• Soft diet with liquid supplements may be needed
• Chorea is the most evident feature of HD
• Depression is the most common specific psychiatric disorder in HD

 

Expected outcome:

• There is no cure for Huntington's disease
• Progressive impairment
• Persons with HD usually die within 15 to 20 years

 

2. Scales and Table

• Clinical features of Huntington's disease
• Clinical stages of Huntington's disease
• Interpretation of genetic testing for CAG repeats

 

References:

Core Resources:

• Compendium of Pharmaceuticals and Specialties (CPS). Canadian Pharmacist association. Toronto: Webcom Inc. 2012
• Day RA, Paul P, Williams B, et al (eds). Brunner & Suddarth's Textbook of Canadian Medical-Surgical Nursing. 2^nd ed. Philadelphia: Lippincott Williams and Wilkins; 2010
• Foster C, Mistry NF, Peddi PF, Sharma S, eds. The Washington Manual of Medical Therapeutics. 33^rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010
• Gray J, ed. Therapeutic Choices. Canadian Pharmacists Association. 6^th ed. Toronto: Webcom Inc. 2011
• Katzung BG, Masters SB, Trevor AJ, eds. Basic and Clinical Pharmacology. 11^th ed. New York: McGraw-Hill; 2009
• Longo D, Fauci A, Kasper D, et al (eds). Harrison's Principles of Internal Medicine. 18^th ed. New York: McGraw-Hill; 2011
• Management of thyroid dysfunction during pregnancy and postpartum. An endocrine society clinical practice guidelines. 2007 J Clin Endocrinol Metab:92 ; S1-S47
• McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis & Treatment. 49^th ed. New York: McGraw-Hill; 2010
• Pagana KD, Pagana TJ eds. Mosby's Diagnostic and Laboratory Test Reference. 9^th ed. St. Louis: Elsevier-Mosby; 2009
• Skidmore-Roth L. ed. Mosby's drug guide for nurses. 9^th ed. St. Louis: Elsevier-Mosby; 2011
• Skidmore-Roth L, ed. Mosby's nursing drug reference. 24^th ed. St. Louis: Elsevier-Mosby; 2011

 

• Online Resourses:
  • http://bjp.rcpsych.org/content/149/6/682
  • http://www.ncbi.nlm.nih.gov/books/NBK1305/
  • http://www.hdfoundation.org/html/testwfn.php
  • http://www.hdac.org/features/article.php?p_articleNumber=519
  • http://www.huntingtonsociety.ca/english/content/?page=91
  • http://www.hdac.org/features/article.php?p_articleNumber=519
  • http://ghr.nlm.nih.gov/gene/HTT
  • www.wemove.org

 

Online Pharmacological Resources:

• e-Therapeutics
• Lexicomp
• RxList
• Epocrates

 

Journals/Clinical Trials:

• Bonelli RM, Wenning GK. Pharmacological management of Huntington's disease: an evidence-based review. Curr Pharm Des 2006; 12:2701
• de Yebenes JG, Landwehrmeyer B, Squitieri F, Reilmann R, Rosser A, Barker RA, Saft C, Magnet MK, Sword A, Rembratt A, Tedroff J; MermaiHD study investigators.Pridopidine for the treatment of motor function in patients with Huntington's disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2011 Dec; 10(12):1049-1057
• Duff K, Paulsen J, Mills J, et al. Mild cognitive impairment in prediagnosed Huntington disease. Neurology 2010; 75:500
• Gil JM, Rego AC. Mechanisms of neurodegeneration in Huntington's disease. Eur J Neurosci 2008; 27:2803
• Huntington Study Group (HSG) A Phase III, Randomized, Double-Blind, Placebo-Controlled, Safety and Efficacy Study of Dimebon in Patients with Mild-To-Moderate Huntington Disease (http://www.hdsa.org/research/clinical-trials/ongoing-clinical-trials/dimebontrial.html)
• Kegelmeyer D, Fritz N, Kostyk S, Kloos A, et al. The effect of video game-based exercise on dynamic balance and mobility in individuals with Huntington's disease. J Neurol Neurosurg Psychiatry 2010;81:A40 doi:10.1136/jnnp.2010.222661.4
• Leigh RJ, Newman SA, Folstein SE, et al. Abnormal ocular motor control in Huntington's disease. Neurology 1983; 33:1268
• Mestre T, Ferreira J, Coelho MM, et al. Therapeutic interventions for symptomatic treatment in Huntington's disease. Cochrane Database Syst Rev 2009;CD006456
• Ondo WG, Tintner R, Thomas M, Jankovic J. Tetrabenazine treatment for Huntington's disease-associated chorea. Clin Neuropharmacol 2002; 25:300
• Potter NT, Spector EB, Prior TW. Technical standards and guidelines for Huntington disease testing. Genet Med 2004:6:61-65
• Pringsheim T, Wiltshire K, Day L, et al. The incidence and prevalence of Huntington's disease: a systematic review and meta-analysis. Mov Disord 2012; 27:1083
• Seneca S, Fagnart D, Keymolen K, et al. Early onset Huntington disease: a neuronal degeneration syndrome. Eur J Pediatr 2004; 163:717
• Walker FO. Huntington's disease. Lancet 2007; 369:218
• Warby SC, Graham RK, and Hayden MR. Huntington Disease. NCBI Bookshelf. Initial Posting: October 23, 1998; Last Update: April 22, 2010