REVIEW

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Managing chorea in
Huntingtonsdisease

Okeanis Vaou1 & Samuel Frank1

Practice Points

Huntingtons disease (HD) is an autosomal, dominantly inherited, neurodegenerative disorder

characterized by progressive motor dysfunction, abnormal involuntary movements, emotional
disturbances and cognitive decline.

The mutation responsible for HD is an expanded CAG repeat on chromosome 4 in the huntingtin gene
(Htt). Only experienced clinicians should perform genetic testing.

One of the earliest pathological changes in HD is the loss of the medium spiny neurons in the caudate
nucleus; however, there are changes found throughout the cortex and basal ganglia.

Chorea is involuntary, excessive, rapid, brief movements that flow between body parts and may lead to
social withdrawal, injury, falls or poor positioning.

Medical treatment options to reduce chorea include a dopamine-depleting agent, neuroleptics,

N-methyl-d-aspartate (NMDA) antagonists, g-aminobutyric acid (GABA) inhibitors and cannabinoids.

Tetrabenazine, a vesicular monoamine transporter 2 inhibitor is the only US FDA-approved medication

for chorea associated with HD; however, other agents are in development.

HD is a progressive disorder that is constantly changing. Treatment of chorea may be less of an issue at
certain points during the disease process, as dystonia and bradykinesia become more prominent and
when behavioral and cognitive issues predominate.

SUMMARY Huntingtons disease (HD) is an inherited, neurodegenerative disorder

characterized by progressive motor dysfunction, abnormal involuntary movements, emotional
disturbances and cognitive decline. There is currently no treatment to modify the progression of HD.
Until disease modifying agents are established, symptomatic treatment remains the cornerstone
of management. Treating chorea and other motor symptoms may improve the quality of life of
sufferers. Multiple interventions have been studied for the treatment of chorea, but tetrabenazine
is the only US FDA-approved drug indicated for the treatment of chorea associated with HD. In this
article, medications available for the treatment of chorea will be summarized and investigational
interventions for the management of chorea will also be briefly reviewed. Although chorea only
constitutes part of HD, the movements can be disabling, injurious or bothersome.

1
Boston Medical Center, 72 East Concord St, C3, Boston, MA 02118, USA

Author for correspondence: Tel.: +1 617 638 8647; Fax: +1 617 638 5354; samfrank@bu.edu

10.2217/NMT.11.40 2011 Future Medicine Ltd Neurodegen. Dis. Manage. (2011) 1(4), 295306 ISSN 1758-2024 295
Review Vaou & Frank
Huntingtons disease (HD) is an autosomal,
dominantly inherited, neurodegenerative dis-
order characterized by progressive motor dys-
function, abnormal involuntary movements,
emotional disturbances and cognitive decline.
The disease is currently diagnosed based on a
constellation of motor signs, including the clini-
cal hallmark, chorea. Chorea is defined as invol-
untary, excessive, rapid, brief movements that
flow between body parts (SupplementaryVideo1)
(see online www.futuremedicine.com/doi/
suppl/10.2217/nmt.11.40). George Huntington
was the first to clearly describe HD in the
English literature in his 1872 essay On
Chorea[1] . The gene responsible for HD codes
for an expanded CAG (glutamine) repeat expan-
sion in exon 1 of the huntingtin (htt) gene at
the location 4p16.9 [2] . In normal individuals,
the CAG repeats are typically fewer than 30.
Generally, most patients with 39 repeats will
develop clinical signs of HD, and the penetrance
rate is reduced with each downward step in the
number of repeats [3] ; there are case reports of
individuals with as few as 29 repeats expressing
the disease[4] . There is a strong inverse relation-
ship between the age of onset of HD and the
number of CAG repeats [5] . The exact function
of htt is unknown, but it may be involved in
intracellular signaling and trafficking, regula-
tion of transcription or may have anti-apoptotic
properties [6] . There is some evidence to suggest
that the binding of the Ras homolog enriched in
striatum (Rhes) protein to htt may be necessary
to cause cellular toxicity [7] .
There is no treatment to modify the progres-
sion of HD. However, treating some of the dis-
ruptive symptoms of HD, such as chorea, may
provide significant benefit to the patients motor
function, quality of life and safety [811] .
Pathogenesis
The earliest and most striking neuropathologi-
cal changes in HD are found in the neostriatum
and cerebral cortex, particularly the caudate
nucleus, with subsequent progression to the
remainder of the basal ganglia. The main vis-
ible pathology of HD are neuronal intranuclear
and cytoplasmic inclusions of mutant htt pro-
tein aggregates. However, there is recent debate
as to whether the inclusions, soluble forms or
a distinct process may actually cause neuronal
dysfunction.
There
are multiple theories pro-
posed regarding the pathogenesis of HD, most
of which suggest that a combination of different
296 Neurodegen. Dis. Manage. (2011) 1(4)
mechanisms such as transcriptional dysregula-
tion, mitochondrial dysfunction with altered
energy metabolism, excitotoxicity, changes
in axonal transport and synaptic dysfunction
contribute to the disorder. Pathological stud-
ies have suggested that the earliest changes
associated with HD consist of degeneration of
striatosubstantia nigra pars compacta neurons,
followed by striatoglobus pallidus externa and
striatosubstantia nigra reticulata neurons and,
finally, striatoglobus pallidus interna neu-
rons [12,13] . The earliest degenerative changes,
the loss of medium sized spiny neurons contain-
ing calbindin, g-aminobutyric acid (GABA),
enkephalin and substanceP, occur in the dor-
somedial aspect of the caudate and putamen [14] .
The enkephalin neurons appear to die before
the substance P neurons. By contrast, the spiny
striatal cholinergic and somatostatin-containing
interneurons are spared. The preferential loss
of enkephalinergic striatal neurons correlates
with the appearance of chorea [15] . Loss of sub-
stance P/dynorphin neurons correlates with
the increase in dystonia in the later stage of the
disease. Other neuropeptide alterations in HD
include a decrease in cholecystokinin, and met-
enkephalin and an increase in somatotstatin,
thyrotropin-releasing hormone, neurotensin and
neuropeptide Y. Prior to any clinical signs, in
addition to the loss of cannabinoid (CB) recep-
tors, there is also loss of adenosine A2a receptor
binding and an increase in GABA-A receptor
binding in the globus pallidum pars interna. As
the disease progresses, there is typically a loss
of dopamine (DA) D1 receptors in the striatum
as well as CB and D1 in the substantia nigra,
eventually involving the rest of the basal ganglia.
Epidemiology
Most European populations display a prevalence
rate of 37/100,000 [16] . However, a recent study
suggests that the prevalence of HD may be as
high as 12.4/100,000 [17] . In Chinese popula-
tions, HD prevalence is only 0.38/100,000,
and there is inadequate information regarding
black African populations [17] . The distribution
of HD is not homogenous, perhaps owing to a
founder effect in particular regions. There are
well known large populations in Scotland with
a prevalence of 560/100,000 and in the Lake
Maracaibo region of Venezuela with a preva-
lence of 700/100,000 [18,19] . There have been
no widespread epidemiological studies of HD
in the USA since the wide availability of genetic
future science group

testing, but it is estimated that approximately
25,00030,000 individuals have manifest HD,
and a further 150,000250,000 individuals are
at risk for the disorder [16] .
Clinical symptoms of HD
Typically, patients become symptomatic in the
third and fourth decade, impacting men and
women equally. Approximately 510% of cases
are classified as juvenile onset, with symptoms
presenting before 20years of age. The vast major-
ity of juvenile cases are inherited paternally and
patients may exhibit more Parkinsonian signs
of bradykinesia, dystonia, tremors and a cogni-
tive deficit, instead of chorea as the predominant
movement disorder [20] . Progressive functional
decline, dementia, motor impairment, dysphagia
and incontinence eventually lead patients with
HD to institutionalization and death from
complications of immobility such as aspira-
tion pneumonia, infections, skin breakdown
and poor nutrition. The average length of life
from onset of symptoms to death ranges from
1520years, but can be shorter when dystonia
and bradykinesia predominate [21] . In patients
with early symptoms or change in functional
status, suicide needs to be considered since 25%
of HD patients attempt suicide and is the cause
of death in 89% of patients [22,23] .
Cognitive decline and psychiatric symp-
toms are also cardinal features of HD patients.
Behavioral dyscontrol can be a very disabling
symptom of HD, causing distress to the patient,
family and caregivers. Although the motor signs
are necessary for diagnosis and remain the most
overt signs of HD, depressive mood changes
and functional disability matter most in health-
related quality of life in patients with HD [24] .
Environmental approaches and cognitive inter-
ventions are key treatments but pharmacological
agents can augment disruptive behaviors, depres-
sion, anxiety and obsessive-compulsive behav-
iors. Caution is advised when relying on medica-
tions for these issues to avoid oversedation and
apathy, already too common in HD patients.
In addition to cognitive and behavioral issues,
chorea may become a safety issue with larger
amplitude movements, causing injury, poor
positioning, skin injuries or even fractures and
head trauma. Patients may not be aware of cho-
rea or the extent of the chorea, but it may cause
distress for the patient or caregiver. Objects
in the house may need to be moved to mini-
mize injuries resulting from chorea. In medical
future science group
Managing chorea in Huntingtonsdisease Review
settings, hospital staff may misinterpret move-
ments to be purposeful, when in fact the chorea
is not voluntary. Small voluntary movements
can become large amplitude owing to chorea
and a lack of modulation of the motor system.
The large amplitude movements may cause diffi-
culty with routine aspects of care, such as dress-
ing, bathing or repositioning. Weight loss is far
too common in HD and excessive movements
may burn additional calories, making eating or
feeding patients more difficult.
Chorea is typically measured using
the total maximal chorea score from the
Unified Huntingtons Disease Rating Scale
(UHDRS) [25] . The item on this scale rates the
amplitude and frequency of chorea in all four
limbs, the trunk, face and buccalorallin-
gual regions. Movements are recorded as the
maximum frequency and amplitude observed
throughout the time clinicians spend with
patients. Excessive abnormal involuntary move-
ments can also be assessed using the Abnormal
Involuntary Movement Scale [26] .
Agents studied for chorea in HD
There are other comprehensive recent reviews
of agents studied to treat chorea [2729] ; there-
fore this article will focus on commonly consid-
ered interventions. The majority of treatments
for chorea have focused on altering DA in the
basal ganglia. However, as our understanding
of the many neurotransmitters involved in HD
expands, treatments may also expand beyond
those that focus solely on DA. Many agents and
surgical procedures have been evaluated in HD
for their efficacy in suppressing chorea, includ-
ing DA-depleting agents, DA antagonists, DA
stabilizing agents, benzodiazepines, glutamate
antagonists, acetylcholinesterase inhibitors, DA
agonists, antiseizure medications, CBs, lithium,
deep brain stimulation and fetal cell transplan-
tation. In this article, we will focus on the agents
that have been studied with some suggestion
of benefit on chorea (Table 1) . The most com-
monly reported or most serious side effects are
summarized in Table 2 .
Dopamine-depleting agents
Tetrabenazine (TBZ) is the only US FDA-
approved drug for HD, indicated for the treat-
ment of chorea associated with HD. TBZ
functions by inhibiting vesicular monoamine
transporter 2 (VMAT2) binding, preventing the
presynaptic release of monoamines and causing
www.futuremedicine.com 297
Review Vaou & Frank
Table 1. Agents studied or reported to have beneficial effects on chorea.
Class Medication(s)
Dopamine depleter Tetrabenazine
Older neuroleptics Haloperidol, risperidone, sulpiride and tiapride
Newer neuroleptics Aripiprazole and olanzapine
Dopamine agonists Lisuride and apomorphine
Cholinesterase inhibitors Galantamine and rivastigmine
NMDA antagonists Amantadine, lamotrigine, memantine and riluzole
Cannabinoids Nabilone
GABA inhibitors Clonazepam
GABA: g-aminobutyric acid; NMDA: N-methyl- d -aspartate.
a functional depletion. Unlike reserpine, the
effects of TBZ are reversible, last hours and are
not modified by long-term treatment [30,31] . To
date, reduced neurodegeneration has not been
documented in human patients exposed to TBZ.
Reserpine binds to both VMAT1 and VMAT2,
with VMAT1 accounting for the peripheral side
effects such as hypotension anddiarrhea.
In a double-blind, placebo-controlled trial,
TBZ was demonstrated to be an effective anti-
choreic drug [32,33] . In this study, TBZ was
titrated weekly in 12.5 mg increments to a
maximum of 100 mg/day or the development
of intolerable adverse effects. Approximately
50% of TBZ-treated patients had a six point
or greater improvement on the UHDRS total
maximal chorea score, compared with 7% of
placebo subjects. The most frequent adverse
effects noted were drowsiness/somnolence,
insomnia, depressed mood, agitation, akathisia
and hyperkinesia. Fatigue was reported as the
most common side effect amongst the subjects
completing the study. In the extension study,
dysarthria was also significantly increased at
80weeks compared with baseline. There was
one suicide in the double-blind study in a sub-
ject taking TBZ. Depression is common and
depressed mood can be exacerbated by TBZ.
However, suicidality in HD does not neces-
sarily correlate with severity of depression and
may also be related to impulsiveness, aggres-
sion, obsessive-compulsive behavior, change in
functional status and a variety of socioeconomic
factors. Nevertheless, all patients taking TBZ
need to be monitored for signs of depressed
mood and suicidal ideation or tendencies.
Neuroleptics
Drugs that block DA receptors are commonly
considered for the management of chorea in
HD owing to their combined ability to reduce
298 Neurodegen. Dis. Manage. (2011) 1(4)
chorea, improve psychosis and increase weight.
Given the frequency of their use, there are sur-
prisingly few double-blind, placebo-controlled
studies evaluating the efficacy and safety of
suchagents.
Older neuroleptics
Haloperidol was found to have no effect
on chorea in a double-blind, randomized,
cross-over study of six patients with HD [34] .
There was worsened depression reported but
improved chorea in a single-blind study of 13
HD patients[35] . Another study of haloperidol
in 20subjects studied the relationship between
serum haloperidol and improvement in abnor-
mal movements [36] . Again, there was signifi-
cant improvement of abnormal movements as
demonstrated by the greater than 30% reduc-
tion from baseline (this study, like many early
trials, was completed prior to the availability
of the UHDRS). The improvement occurred
at serum concentrations that corresponded to
doses of 1.510 mg/day. Clinically, the most
problematic side effects of haloperidol and
the older neuroleptics are sedation, cognitive
slowing, increased mobility problems, apathy,
akathisia, dysphagia, tardive dyskinesia and
worsened orthostatic hypotension. Apathy and
akathisia can be particularly problematic in
patients with HD, as they may not have the
insight to recognize these problems or the
side effects may be wrongly attributed to HD.
Behavior with poor attention and inability to
complete even simple tasks may be the only sign
of akathisia in HD. Tardive dyskinesia can be
difficult to diagnose in HD, but if there are
new movements, particularly periorally, tar-
dive movements need to be considered. Older
neuroleptics do not necessarily improve func-
tional capacity, despite ameliorating chorea, in
part explained by the possibility of suppressed
voluntary motor activity [36] .
There are no clinical trials of risperidone
but a few reports suggest a positive effect on
the disease with a tolerable adverse-effect pro-
file[3740] . A retrospective chart review study in
17 patients taking risperidone and 12 patients
not taking risperidone suggested that the use
of risperidone significantly improved motor
symptoms [41] .
Sulpiride improved movement scores but
not functional status in a randomized, dou-
ble-blind, cross-over trial [42] . This drug is not
currently available in the USA but may cause
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 Managing chorea in Huntingtonsdisease Review

less tardive dyskinesia than the other older
neuroleptics. Tiapride improved chorea com-
pared with placebo, but did not significantly
reduce involuntary movements overall in a
double-blind, placebo-controlled, cross-over
study [43,44] .
Newer neuroleptics
limited owing to adverse events such as drow-
Owing to their relatively better tolerability,
atypical neuroleptics have been evaluated for
the treatment of chorea in HD. Quetiapine has
been tested in multiple, small, uncontrolled,
nonrandomized trials for HD with some suc-
cess on psychiatric symptoms, but little impact
on chorea [4547] . Quetiapine was well tolerated
at starting doses 2550 mg/day and titrated
upward to 2550mg/week.
Clozapine was studied in HD for 31days after
a rapid titration to 150mg/day. The study was
siness, fatigue, anticholinergic symptoms and
walking difficulties. The adverse events occurred
without beneficial effects [48] . Another study dem-
onstrated improvement in chorea in a dosage of

Table 2. Common or serious side effects reported for medications used for chorea.
Medication Side effects
Dopamine depleters
Tetrabenazine Drowsiness/somnolence, insomnia, depressed mood (including suicidality), agitation,
akathisia, fatigue and dysarthria
Older neuroleptics
Haloperidol Sedation, depression, cognitive slowing, increased mobility problems, apathy,
akathisia, dysphagia, tardive dyskinesia and worsened orthostatic hypotension
Risperidone Sedation and increased appetite
Sulpiride Sedation and akathisia
Tiapiride Sedation and extrapyramidal signs
Newer neuroleptics
Quetiapine Hypotension, syncope and tardive dyskinesia
Clozapine Drowsiness, fatigue, anticholinergic symptoms, walking difficulties, hypotension,
confusion and agranulocytosis
Olanzapine Weight gain and sedation
Aripiprazole Akathisia, tardive dyskinesia and dystonia
Dopamine agonists
Apomorphine Nausea and sedation
Lisuride Nausea, hypotension, confusion, drowsiness and hallucinations
Cholinesterase inhibitors
Rivastigmine Nausea and vomiting
Galantamine Nausea and vomiting
Donepezil Diarrhea, sedation, fatigue, vomiting and anorexia
NMDA antagonists
Amantadine Irritability, aggressiveness, confusion and hallucinations
Memantine Sedation, worsening of balance and speech and confusion
Riluzole Fatigue, urinary incontinence and diaphoresis
Remacemide Nausea, vomiting and dizziness
Lamotrigine Nausea, dizziness, headache, skin rash, depression, insomnia and night sweats, as well
as mild increase in liver enzymes
Canabinoids
Nabilone Drowsiness, forgetfulness and paranoia
GABA inhibitors
Clonazepam Sedation
GABA: g-aminobutyric acid.

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Review Vaou & Frank
200 mg/day, with some subjects receiving as
much as 500mg/day, but again side effects such
as somnolence, hypotension and confusion inter-
fered with daily activities [49] . The high side effect
profile and the frequent monitoring of the white
blood cell count, make this an unfavorable medi-
cation for the treatment of chorea in HD patients.
There are a few small open-label studies
examining the use of olanzapine for treating
chorea [5052] . Olanzapine may be a good treat-
ment for the psychiatric symptoms of HD and
is moderately effective for motor symptoms [55] .
Weight gain is a prominent side effect in the use
of this drug for the treatment of psychiatric dis-
ease, which may be of benefit to patients with
HD who are losing weight. The range of effect
on chorea has been 066% reduction [5256] .
Olanzapine was generally well tolerated at doses
of 520mg per day with sedation being the
most common CNS side effect.
Aripiprazole, an antipsychotic with a partial
agonist effect on D2 and 5-hydroxytryptamine
(5HT)-1A receptors, and an antagonistic effect
on 5HT-2A, has been studied in HD in a few
small trials. Overall, the drug was well tolerated
and reduced chorea to a degree equivalent to that
of TBZ. Although aripiprazole was found to
have fewer adverse effects on mood than TBZ,
it is important to bare in mind that it may be
associated with akathisia, tardive dyskineisa/
dystonia and neuroleptic malignant syndrome,
similar to other typical and atypical neuroleptic
agents[5759] .
Dopamine agonists
Lisuride and apomorphine brought about a tran-
sient improvement of chorea, lasting approximately
1h. However, the pharmacological rationale for
the use of DA agonists in the treatment of chorea
is unclear, presumably they act by activating the
presynaptic DA receptors, leading to decreased
DA turnover. In additon, consistent with animal
studies, there is evidence that low doses of apo-
morphine preferentially stimulates self-inhibitory
DA receptors in humans as well[6063] .
Cholinesterase inhibitors
On the basis of the long-term follow-up of HD
patients, rivastigmine 6-mg daily exerted a sig-
nificant improvement of motor performances
over a period of 2years in an open-label, control-
led study, with no significant adverse effects[64] .
Rivastigmine was well tolerated, with nausea and
vomiting being the most common side effects[64] .
300 Neurodegen. Dis. Manage. (2011) 1(4)
In a case report of galantamine up to 24mg/day
for an acute psychotic episode, psychotic symp-
toms and chorea improved in a 35year-old
man [65] . Donepezil has not been demonstrated
to be effective in reducing chorea[66,67] .
NMDA antagonists
Amantadine has been demonstrated to improve
chorea in placebo-controlled, randomized trials
[11,68] . These study results suggest that increased
N-Methyl-d-aspartate (NMDA) receptor sensi-
tivity may contribute to the clinical expression of
chorea in HD and that selective antagonists can
be safely administered and can reduce chorea.
Dosages used in these trials ranged from 300 up
to 400mg daily. Similar to the haloperidol trials,
there was an improvement in chorea that corre-
lated with plasma amantadine levels. However,
even in lower dosages, amantadine may increase
irritability and aggressiveness or cause confu-
sion and hallucinations [11,68,69] . Memantine was
found to significantly reduce chorea in an open-
label study of 12 subjects in doses titrated from
5 to 20mg/day and followed for 3months [70] .
However, despite its use in Alzheimers disease,
memantine failed to improve cognitive, behav-
ioral or functional ratings in HD. Riluzole was
found to reduce chorea at a daily dose of 200mg
but not 100mg in one trial [71] . However, after
adjusting for the concomitant use of neurolep-
tic treatment, this trial failed to demonstrate a
significant effect of Riluzole on chorea treatment
[7174] . Remacemide was an investigational non-
selective NMDA receptor antagonist. In one of
the largest studies to date involving patients with
HD, remacemide failed to demonstrate a sig-
nificant improvement in functional decline and
did not improve chorea [75] . In a double-blind,
placebo-controlled, randomized study of 64 HD
patients, administered lamotrigine, another gluta-
mate-releasing inhibitor, produced a trend toward
decreased chorea at a dose of 400mg/day [76] .
Cannabinoids
Nabilone is a synthetic analogue of D-9-
tetrahydrocannabinol, the major psychoactive
component of cannabis. High densities of CB
receptors in the basal ganglia raise the possibility
that drugs acting upon the CB systems could be
beneficial. In a double-blind, placebo-controlled,
cross-over pilot study, nabilone demonstrated an
improvement in chorea with doses of 12mg/day,
with a suggestion of improving the vague notion
of agitation [77,78] .
future science group

GABA inhibitors
Benzodiazepines are frequently used to treat
anxiety as well as chorea in HD patients. A
case report demonstrated significant improve-
ment in chorea after titration of clonazepam
up to 1mg three times a day [79] . In a study of
three patients, the effective dose of clonazepam
varied up to 5.5mg/day [80] . However, at this
dosage, sedation became a significant adverse
effect. In a placebo-controlled trial, baclofen was
found to be ineffective for HD in doses of up to
60mg/day[81] .
Other interventions
In three double-blind, placebo-controlled trials,
lithium did not seem to be of therapeutic value
for motor or nonmotor symptoms in HD [35,82,83] .
There have been a few case reports of the use
of deep brain stimulation (DBS) for chorea in
patients with HD [8486] . In general, there are
positive results of bilateral globus pallidus pars
interna stimulation with the best clinical effects
on chorea obtained with high-frequency stimu-
lation. Stimulation at a lower frequency resulted
in worsening of the hyperkinetic movements but
improvement of bradykinesia. In a case report,
4years after bilateral globus pallidus pars interna
DBS surgery, the improvement of chorea remained
stable [87] . Appropriate selection of the best can-
didates for DBS is challenging given the variable
disease course and cognitive decline.
Neural transplantation has been proposed as a
potential treatment for those neurodegenerative
diseases in which there is regional cell loss. There
have been multiple, small, open-label clinical stud-
ies assessing the safety and efficacy of fetal and
porcine cell transplantation in the treatment of
chorea in HD patients but the technique, location
of inoculation, cell type and other factors continue
to be studied [8890] . In a study of five patients
with fetal neural transplants, clinical improvement
leveled off after 2years and then faded variably
46 years after surgery. Dystonia deteriorated
consistently, whereas chorea did not[91] .
Interventions under investigation
Pridopidine is the first drug in a new class of
therapeutic agents termed dopaminergic stabiliz-
ers, which has completed a PhaseIII trial with
positive results. In a trial of 437 HD subjects
treated with 45mg of pridopidine once or twice
daily for 26weeks, there was an improvement in
voluntary motor function and some involuntary
motor symptoms. Although pridopidine reduced
future science group
Managing chorea in Huntingtonsdisease Review
dystonia, there was little effect on chorea. The
medication was well tolerated, with a safety profile
similar to that of placebo [92] .
How to choose a medication for chorea
There are many choices of treatment options for
chorea when it becomes bothersome or injurious.
If there is clear bradykinesia, amantadine may
be the best choice since it may address some of
the underlying slowness. When weight loss is an
issue, medications such as olanzapine or a CB
that have known weight gain or appetite stimu-
lant properties may be preferred. When there are
significant mood-related issues, aripiprazole may
be the drug of choice. Currently, there is the best
evidence for TBZ, and this agent remains the only
FDAapproved medication in the USA.
Huntingtons disease is a disease that is con-
stantly changing. Typically, during the middle
and advancing stages of HD, chorea temporar-
ily becomes less of an issue as bradykinesia, gait
imbalance and dystonia become more prominent.
In more advanced stages of the disease, chorea
often re-emerges and becomes a movement that
is higher in amplitude but lower in frequency than
earlier in the disease process. When chorea is less
of a significant issue, the medications for chorea
need to be reassessed rather than simply continued
owing to inertia of care. Some of the medications
can have akathisia, dysphagia, dysarthria or other
side effects that can impact quality of life in later
stages of the disease. At that point, all medications,
including those for chorea should be reconsidered.
Conclusion & future perspective
Huntingtons disease is a devastating, fatal neu-
rodegenerative disease. The movements associ-
ated with HD are the most overt signs of the dis-
ease, and the aspect that can be addressed best.
There are many agents to choose from, but every
patient needs careful individual assessment by
clinicians familiar with HD to help decide
whether a medication for chorea is needed and
which one is best suited for that patient (Table3) .
The future of treating this disease will need to
focus beyond the movement disorder. Of course,
altering the onset and progression of the disease
is the ultimate goal. In the interim, the cog-
nitive and behavioral aspect of the disease is
vastly understudied and there are few effective
medical interventions at present. Over the next
510years, we speculate that other treatments
for the disease as a whole will be in development.
New technologies that use cell/gene transfer,
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Review Vaou & Frank

Table 3. Abbreviated summary of medications used for chorea.

Mechanism of action Study design Dosage range Effect on measure No. Ref.
actively
treated
Dopamine depleters
Tetrabenazine Inhibition of VMAT2 Double-blind, placebo- 12.5100mg/day 3.5-point reduction in UHDRS-c 54 [32]
binding controlled trial
Older neuroleptics
Haloperidol Antagonizes dopamine D2 Double-blind, 1.510mg/day Positive improvement of subjective 6 [35]
receptors randomized, crossover impression
study
Single-blinded study Positive improvement of subjective 13 [34]
impression
Unblinded 140mg/day 30% improvement of abnormal 20 [36]
movements
Risperidone Antagonizes dopamine D2 Case reports 24mg/day Positive improvement of subjective 17
receptors and serotonin impression
5-HT2 receptors Chart review Positive improvement of subjective [41]
impression
Sulpiride Selective dopamine D2, Randomized double- 3001200mg/day Reduction in median movement 11 [42]
D3 receptor antagonist blind cross-over trial count on the Chorea Severity Score

Tiapiride Selective D2 receptor Double-blind, placebo- 3mg/day Positive improvement of subjective 23 [43]
antagonist controlled cross-over impression
study
Double-blind controlled No improvement of subjective 22 [44]
cross-over trial impression with video
Newer neuroleptics
Quetiapine Antagonizes dopamine D2 Case reports 25600mg/day No improvement of
receptors and serotonin subjectiveimpression
5-HT2 receptors
Clozapine Dopamine D1, D4 Double-blind, 150mg/day Reduction in chorea in naive 26 [48]
and serotonin 5-HT2, randomized trial patients on AIMS, UHDRS and video
cholinergic muscarinic Double-blind, A marked decrease in movements 2 [49]
receptor antagonist placebocontrolled trial
Olanzapine Antagonizes dopamine D2 Prospective open-label 520mg/day 44-point reduction on UHDRS 9 [52]
receptors and serotonin study
5-HT2 receptors Open-pilot study 5mg No significant reduction in 11 [56]
UHDRS-c, but improved behavioral
score
Aripiprazole Partial dopamine D2 Cross-over study 10.76 5.2-point reduction of UHDRS-c 6 [57]
receptor agonist and 4.91mg/day
serotonin 5-HT1,
5-HT2 receptor antagonist
5-HT: 5-hydroxytryptamine; ADAS: Alzheimers Disease Assessment Scale; AIMS: Abnormal Involuntary Movement Scale; GABA: g-aminobutyric acid; IM: Intramuscular;
NMDA:N-Methyl- d -aspartate; TFC: Total functional capacity; UHDRS:Unified Huntingtons Disease Rating Scale; UHDRS-c: Unified Huntingtons Disease Rating Scale chorea score;
VMAT2: Vesicular monoamine transporter 2.

302 Neurodegen. Dis. Manage. (2011) 1(4) future science group

 Managing chorea in Huntingtonsdisease Review

Table 3. Abbreviated summary of medications used for chorea (cont.).

Mechanism of action Study design Dosage range Effect on measure No. Ref.
actively
treated
Dopamine agonists
Apomorphine Nonselective dopamine Double-blind, Continuous 6-point reduction of UHDRS-c and 5 [62]
D1, D2 receptor agonist randomized, crossover infusion of 34.4% reduction in AIMS score
study 1020g/kg
bodyweight
Case reports 14mg/day IM 4085% reduction in AIMS score 5 [63]
Lisuride Dopamine D2, D3, D4 Open-label study 150mg/day Positive improvement of subjective 11 [61]
receptor and serotonin impression
5-HT1A, 5-HT2A/C
receptor partial agonist
Cholinesterase inhibitors
Rivastigmine Butylcholin-esterase and Open-label, controlled 6mg/day Improvement in Marsden and 11 [64]
acetylcholin- esterase study Quinn Chorea Severity Scale, TFC,
inhibition UHDRS-motor and AIMS
Galantamine Reversible cholinesterase Case report Up to 24mg/day Positive improvement of subjective 1 [65]
inhibitor impression
Donepezil Reversible cholinesterase Open-label study 10mg No change in UHDRS or ADAS 12 [67]
inhibitor
NMDA antagonists
Amantadine NMDA receptor Open-label study 300400mg/day Improved UHDRS and AIMS 8 [68]
antagonist
Double-blind Up to 400mg/day 36% reduction in UHDRS-c, 56% 22 [11]
placebocontrolled reduction in UHDRS-c for those
cross-over study with highest plasma levels
Memantine NMDA receptor Open-label study 520mg/day 11.5 6.3 to 4.8 3.8 improvement 12 [70]
antagonist of UHDRS-c
Riluzole NMDA receptor Double-blind 100200mg/day 4.0 7.1 UHDRS motor unit 41 [71]
antagonist, inhibitory multicenter trial reduction
effect on glutamate Randomized No change in UHDRS 251 [72]
release doubleblind trial
Open-label trial 35% reduction of UHDRS-c 8 [73]

Open-label study 2830% reduction of UHDRS-c at 9 [74]

3months, but no sustained effect
Remacemide Nonselective NMDA Multicenter, 200mg No change in UHDRS-c 142 [75]
receptor antagonist randomized, threetimes daily
doubleblind study
Lamotrigine Blocks voltage-activated Double-blinded, 50400 mg/day No change in TFC or Quantified 28 [76]
sodium channels and thus placebo-controlled Neurological Examination
inhibits glutamate release study
in invitro models
Cannabinoids
Nabilone Cannabinoid receptor Double-blind, placebo- 12 mg/day 1.68-unit reduction in UHDRS-c 44 [78]
binding controlled, cross-over
pilot study
GABA inhibitors
Clonazepam Enhances GABA activity Case studies 35.5 mg/day Positive improvement of subjective 3
and binds benzodiazepine impression
receptors
5-HT: 5-hydroxytryptamine; ADAS: Alzheimers Disease Assessment Scale; AIMS: Abnormal Involuntary Movement Scale; GABA: g-aminobutyric acid; IM: Intramuscular;
NMDA:N-Methyl- d -aspartate; TFC: Total functional capacity; UHDRS:Unified Huntingtons Disease Rating Scale; UHDRS-c: Unified Huntingtons Disease Rating Scale chorea score;
VMAT2: Vesicular monoamine transporter 2.

future science group www.futuremedicine.com 303

Review Vaou & Frank

neurotrophic factors or silencing RNA will also
probably emerge as potential new therapies. For
the patients and families today who survive with
HD, addressing chorea and other aggravating
symptoms remains the only option. TBZ is per-
haps the best studied, but the choice of medica-
tion depends on the unique situation for each
individual patient.
Financial & competing interests disclosure
S Frank has received speaking fees and grant support from
Lundbeck. The authors have no other relevant affiliations
or financial involvement with any organization or entity
with a financial interest in or financial conflict with the
subject matter or materials discussed in the manuscript
apart from those disclosed. No writing assistance was
utilized in the production of thismanuscript.

7 Subramaniam S, Sixt KM, Barrow R, 19 Simpson SA, Johnston AW. The prevalence
Bibliography SnyderSH. Rhes, a striatal specific protein, and patterns of care of Huntingtons chorea in
Papers of special note have been highlighted as: mediates mutant-huntingtin cytotoxicity. Grampian. Br. J. Psychiatry 155, 799804
n
of interest Science 324(5932), 13271330 (2009). (1989).
of considerable interest
n n

8 Andrich J, Saft C, Ostholt N, Muller T. 20 Ribai P, Nguyen K, Hahn-Barma V etal.

1 Huntington G. On chorea. George
Huntington, M.D. J. Neuropsychiatry Clin.
Neurosci. 15(1), 109112 (2003).
n
A modern reproduction of the first
description of chorea in the English
language. George Huntington was not the
first, but he was the first to describe the
disease in a widelypublished
Englishjournal.
2 A novel gene containing a trinucleotide
repeat that is expanded and unstable on
Huntingtons disease chromosomes. The
Huntingtons disease collaborative research
group. Cell 72(6), 971983 (1993).
n n
This groundbreaking paper was the
culmination of an extensive collaborative
effort to find the gene that causes
Huntingtons disease (HD).
3 ACMG/ASHG statement. Laboratory
guidelines for Huntington disease genetic
testing. The american college of medical
genetics/american society of human genetics
Huntington disease genetic testing working
group. Am. J. Hum. Genet. 62(5), 12431247
(1998).
n
The information in this paper remains the
established standard in guidelines for
genetic testing inHD.
4 Kenney C, Powell S, Jankovic J. Autopsy-
proven Huntingtons disease with 29
trinucleotide repeats. Mov. Disord. 22(1),
127130 (2007).
5 Snell RG, MacMillan JC, Cheadle JP etal.
Relationship between trinucleotide repeat
expansion and phenotypic variation in
Huntingtons disease. Nat. Genet. 4(4),
393397 (1993).
6 Nucifora FC Jr, Sasaki M, Peters MF etal.
Interference by huntingtin and atrophin-1
with cbp-mediated transcription leading to
cellular toxicity. Science 291(5512),
24232428 (2001).
Complex movement behaviour and progression
of huntingtons disease. Neurosci.Lett. 416(3),
272274 (2007).
9 Bates G. Huntingtin aggregation and toxicity
in Huntingtons disease. Lancet361(9369),
16421644 (2003).
10 Frank S, Marshall F, Plumb S etal. Functional
decline due to chorea in Huntingtons disease.
Neurology 56(Suppl. 3), A204 (2004).
11 Verhagen ML, Morris MJ, Farmer C etal.
Huntingtons disease, a randomized, controlled
trial using the NMDA-antagonist amantadine.
Neurology 59(5), 694699 (2002).
12 Hedreen JC, Folstein SE. Early loss of
neostriatal striosome neurons in Huntingtons
disease. J. Neuropathol. Exp. Neurol. 54(1),
105120 (1995).
13 Albin RL. Selective neurodegeneration in
Huntingtons disease. Ann. Neurol. 38(6),
835836 (1995).
14 Ferrante RJ, Kowall NW, Richardson EP Jr.
Proliferative and degenerative changes in
striatal spiny neurons in Huntingtons disease: a
combined study using the section-Golgi
method and calbindin D28k
immunocytochemistry. J. Neurosci. 11(12),
38773887 (1991).
15 Albin RL, Reiner A, Anderson KD etal.
Preferential loss of striato-external pallidal
projection neurons in presymptomatic
Huntingtons disease. Ann. Neurol. 31(4),
425430 (1992).
16 Harper PS. The epidemiology of
Huntingtons disease. Hum. Genet. 89(4),
365376 (1992).
17 Spinney L. Uncovering the true prevalence of
Huntingtons disease. Lancet Neurol. 9(8),
760761 (2010).
18 Penney JB Jr, Young AB, Shoulson I etal.
Huntingtons disease in Venezuela: 7years of
follow-up on symptomatic and asymptomatic
individuals. Mov. Disord. 5(2), 9399 (1990).
Psychiatric and cognitive difficulties as
indicators of juvenile huntington disease
onset in 29 patients. Arch. Neurol. 64(6),
813819 (2007).
21 Martin B, Golden E, Keselman A etal.
Therapeutic perspectives for the treatment of
Huntingtons disease: treating the whole body.
Histol. Histopathol. 23(2), 237250 (2008).
22 Farrer LA. Suicide and attempted suicide in
Huntington disease: implications for
preclinical testing of persons at risk.
Am.J.Med. Genet. 24(2), 305311
(1986).
23 Schoenfeld M, Myers RH, Cupples LA,
Berkman B, Sax DS, Clark E. Increased rate
of suicide among patients with Huntingtons
disease. J. Neurol. Neurosurg. Psychiatry
47(12), 12831287 (1984).
24 Ho AK, Gilbert AS, Mason SL,
GoodmanAO, Barker R A. Health-related
quality of life in Huntingtons disease:
Which factors matter most? Mov. Disord.
24(4), 574578 (2009).
25 Huntington Study Group. Unified
Huntingtons Disease Rating Scale:
reliability and consistency. Mov. Disord.
11(2), 136142 (1996).
n
The UHDRS remains the gold standard,
reliable and validated scale to assess and
follow HD in the clinic and clinical trials.
26 ECDEU Assessment Manual for
Psychopharmacology. Guy W (Ed.). United
States Department of Health EaW 534537
Rockville, MD, USA (1976).
27 Bonelli RM, Hofmann P. A review of the
treatment options for Huntingtons disease.
Expert. Opin. Pharmacother. 5(4), 767776
(2004).
28 Frank S, Jankovic J. Advances in the
pharmacological management of
Huntingtons disease. Drugs 70(5), 561571
(2010).

304 Neurodegen. Dis. Manage. (2011) 1(4) future science group


29 Frank S. Tetrabenazine: the first approved
drug for the treatment of chorea in US
patients with Huntington disease.
Neuropsychiatr. Dis. Treat. 6, 657665
(2010).
30 Kenney C, Hunter C, Davidson A,
JankovicJ. Short-term effects of
tetrabenazine on chorea associated with
Huntingtons disease. Mov. Disord. 22(1),
1013 (2007).
31 Scherman D, Henry JP. Reserpine binding to
bovine chromaffin granule membranes.
Characterization and comparison with
dihydrotetrabenazine binding. Mol.
Pharmacol. 25(1), 113122 (1984).
32 Huntington Study Group. Tetrabenazine as
antichorea therapy in Huntington disease: a
randomized controlled trial. Neurology 66(3),
366372 (2006).
33 Frank S. Tetrabenazine as anti-chorea
therapy in Huntington disease: an open-label
continuation study. Huntington Study
Group/TETRA-HD Investigators. BMC
Neurol. 9, 62 (2009).
34 Koller WC, Trimble J. The gait abnormality
of Huntingtons disease. Neurology 35(10),
14501454 (1985).
35 Leonard DP, Kidson MA, Brown JG,
Shannon PJ, Taryan S. A double blind trial of
lithium carbonate and haloperidol in
Huntingtons chorea. Aust. NZ J. Psychiatry
9(2), 115118 (1975).
36 Barr AN, Fischer JH, Koller WC, Spunt AL,
Singhal A. Serum haloperidol concentration
and choreiform movements in Huntingtons
disease. Neurology 38(1), 8488 (1988).
37 Cankurtaran ES, Ozalp E, Soygur H,
CakirA. Clinical experience with
risperidone and memantine in the treatment
of Huntingtons disease. J. Natl Med. Assoc.
98(8), 13531355 (2006).
38 Erdemoglu AK, Boratav C. Risperidone in
chorea and psychosis of Huntingtons disease.
Eur. J. Neurol. 9(2), 182183 (2002).
39 Madhusoodanan S, Brenner R. Use of
risperidone in psychosis associated with
Huntingtons disease. Am. J. Geriatr.
Psychiatry 6(4), 347349 (1998).
40 Parsa MA, Szigethy E, Voci JM, MeltzerHY.
Risperidone in treatment of choreoathetosis
of Huntingtons disease. J.Clin.
Psychopharmacol. 17(2), 134135 (1997).
41 Duff K, Beglinger LJ, ORourke ME,
Nopoulos P, Paulson HL, Paulsen JS.
Risperidone and the treatment of psychiatric,
motor, and cognitive symptoms in
Huntingtons disease. Ann. Clin. Psychiatry
20(1), 13 (2008).
future science group
Managing chorea in Huntingtonsdisease
42 Quinn N, Marsden CD. A double blind trial
of sulpiride in Huntingtons disease and
tardive dyskinesia. J. Neurol. Neurosurg.
Psychiatry 47(8), 844847 (1984).
43 Deroover J, Baro F, Bourguignon RP,
SmetsP. Tiapride versus placebo: a double-
blind comparative study in the management
of Huntingtons chorea. Curr. Med. Res. Opin.
9(5), 329338 (1984).
44 Roos RA, Buruma OJ, Bruyn GW, Kemp B,
van der Velde EA. Tiapride in the treatment
of Huntingtons chorea. Acta. Neurol. Scand.
65(1), 4550 (1982).
45 Alpay M, Koroshetz WJ. Quetiapine in the
treatment of behavioral disturbances in
patients with Huntingtons disease.
Psychosomatics 47(1), 7072 (2006).
46 Bonelli RM, Niederwieser G. Quetiapine in
Huntingtons disease: a first case report.
J.Neurol. 249(8), 11141115 (2002).
47 Seitz DP, Millson RC. Quetiapine in the
management of psychosis secondary to
Huntingtons disease: a case report.
Can.J.Psychiatry 49(6), 413 (2004).
48 van Vugt JP, Siesling S, Vergeer M,
vanderVelde EA, Roos RA. Clozapine versus
placebo in Huntingtons disease: a double
blind randomised comparative study.
J.Neurol. Neurosurg. Psychiatry 63(1), 3539
(1997).
49 Caine ED, Polinsky RJ, Kartzinel R,
EbertMH. The trial use of clozapine for
abnormal involuntary movement disorders.
Am. J. Psychiatry 136(3), 317320 (1979).
50 Laks J, Rocha M, Capitao C etal.
Functional and motor response to low dose
olanzapine in Huntingtons disease: case
report. Arq. Neuropsiquiatr. 62(4),
10921094 (2004).
51 Grove VE Jr, Quintanilla J, DeVaney GT.
Improvement of Huntingtons disease with
olanzapine and valproate. N. Engl. J. Med.
343(13), 973974 (2000).
52 Bonelli RM, Niederwieser G, Tribl GG,
Koltringer P. High-dose olanzapine in
Huntingtons disease. Int. Clin.
Psychopharmacol. 17(2), 9193 (2002).
53 Bonelli RM, Mahnert FA, Niederwieser G.
Olanzapine for Huntingtons disease: an open
label study. Clin. Neuropharmacol. 25(5),
263265 (2002).
54 Dipple HC. The use of olanzapine for
movement disorder in Huntingtons disease:
a first case report. J. Neurol. Neurosurg.
Psychiatry 67(1), 123124 (1999).
55 Paleacu D, Anca M, Giladi N. Olanzapine in
Huntingtons disease. Acta. Neurol. Scand.
105(6), 441444 (2002).
www.futuremedicine.com
Review
56 Squitieri F, Cannella M, Piorcellini A,
BrusaL, Simonelli M, Ruggieri S. Short-term
effects of olanzapine in Huntington disease.
Neuropsychiatry Neuropsychol. Behav. Neurol.
14(1), 6972 (2001).
57 Brusa L, Orlacchio A, Moschella V, Iani C,
Bernardi G, Mercuri NB. Treatment of the
symptoms of Huntingtons disease:
preliminary results comparing aripiprazole
and tetrabenazine. Mov. Disord. 24(1),
126129 (2009).
58 Ciammola A, Sassone J, Colciago C etal.
Aripiprazole in the treatment of Huntingtons
disease: a case series. Neuropsychiatr. Dis.
Treat. 5, 14 (2009).
59 Oulis P, Mourikis I, Konstantakopoulos G,
Papageorgiou SG, Kouzoupis AV. Aripiprazole
in the treatment of olanzapine-resistant
psychotic and motor symptoms of
Huntingtons disease. J. Neuropsychiatry Clin.
Neurosci. 22(3), 352C.E4352C.E5 (2010).
60 Caraceni TA, Girotti F, Giovannini P,
Pederzoli M, Parati EA. Effects of DA agonist
in Huntington disease hyperkinesia. Ital. J.
Neurol. Sci. 1(3), 155161 (1980).
61 Frattola L, Albizzati MG, Alemani A,
BassiS, Ferrarese C, Trabucchi M. Acute
treatment of Huntingtons chorea with
lisuride. J. Neurol. Sci. 59(2), 247253
(1983).
62 Vitale C, Marconi S, Di ML etal. Short-term
continuous infusion of apomorphine
hydrochloride for treatment of Huntingtons
chorea: a double blind, randomized cross-over
trial. Mov. Disord. 22(16), 23592364 (2007).
63 Corsini GU, Onali P, Masala C,
CianchettiC, Mangoni A, Gessa G.
Apomorphine hydrochloride-induced
improvement in Huntingtons chorea:
stimulation of dopamine receptor. Arch.
Neurol. 35(1), 2730 (1978).
64 de TM, Difruscolo O, Sciruicchio V,
Specchio N, Livrea P. Twoyears follow-up of
rivastigmine treatment in Huntington
disease. Clin. Neuropharmacol. 30(1),
4346 (2007).
65 Petrikis P, Andreou C, Piachas A, BozikasVP,
Karavatos A. Treatment of Huntingtons
disease with galantamine. Int.Clin.
Psychopharmacol. 19(1), 4950 (2004).
66 Cubo E, Shannon KM, Tracy D etal. Effect
of donepezil on motor and cognitive
function in Huntington disease. Neurology
67(7), 12681271 (2006).
67 Fernandez HH, Friedman JH, Grace J,
Beason-Hazen S. Donepezil for
Huntingtons disease. Mov. Disord. 15(1),
173176 (2000).
305
Review Vaou & Frank
68 Lucetti C, Gambaccini G, Bernardini S etal.
Amantadine in Huntingtons disease:
open-label video-blinded study. Neurol. Sci.
23(Suppl. 2), S83S84 (2002).
69 Stewart JT. Adverse behavioral effects of
amantadine therapy in Huntingtons disease.
South Med. J. 80(10), 13241325 (1987).
70 Ondo WG, Mejia NI, Hunter CB. A pilot
study of the clinical efficacy and safety of
memantine for Huntingtons disease.
Parkinsonism Relat. Disord. 13(7), 453454.
(2007)
71 Huntington Study Group. Dosage effects of
riluzole in Huntingtons disease: a multicenter
placebo-controlled study. Neurology 61(11),
15511556 (2003).
72 Landwehrmeyer GB, Dubois B,
deYebenesJG etal. Riluzole in Huntingtons
disease: a 3year, randomized controlled
study. Ann. Neurol. 62(3), 262272 (2007).
73 Rosas HD, Koroshetz WJ, Jenkins BG etal.
Riluzole therapy in Huntingtons disease
(HD). Mov. Disord. 14(2), 326330 (1999).
74 Seppi K, Mueller J, Bodner T etal. Riluzole
in Huntingtons disease (HD): an open label
study with one year follow up. J. Neurol.
248(10), 866869 (2001).
75 Huntington Study Group. A randomized,
placebo-controlled trial of coenzyme Q10
and remacemide in Huntingtons disease.
Neurology 57(3), 397404 (2001).
n n
A large trial that was one of the first
toexamine coenzyme Q10 in
neurodegenerative disease. Although there
was no significant effect on slowing disease
progression, other trials in Parkinsons
disease, amyotrophic lateral sclerosis and
HD were based on the results of this trial.
306 Neurodegen. Dis. Manage. (2011) 1(4)
76 Kremer B, Clark CM, Almqvist EW etal.
Influence of lamotrigine on progression of
early Huntington disease: a randomized
clinical trial. Neurology 53(5), 10001011
(1999).
77 Curtis A, Rickards H. Nabilone could treat
chorea and irritability in Huntingtons
disease. J. Neuropsychiatry Clin. Neurosci.
18(4), 553554 (2006).
78 Curtis A, Mitchell I, Patel S, Ives N,
RickardsH. A pilot study using nabilone for
symptomatic treatment in Huntingtons
disease. Mov. Disord. 24(15), 22542259
(2009).
79 Stewart JT. Treatment of Huntingtons disease
with clonazepam. South Med. J. 81(1), 102
(1988).
80 Peiris JB, Boralessa H, Lionel ND.
Clonazepam in the treatment of choreiform
activity. Med. J. Aust. 1(8), 225227 (1976).
81 Shoulson I, Odoroff C, Oakes D etal.
Acontrolled clinical trial of baclofen as
protective therapy in early Huntingtons
disease. Ann. Neurol. 25(3), 252259
(1989).
82 Vestergaard P, Baastrup PC, Petersson H.
Lithium treatment of Huntingtons chorea.
Aplacebo-controlled clinical trial. Acta.
Psychiatr. Scand. 56(3), 183188 (1977).
83 Aminoff MJ, Marshall J. Treatment of
Huntingtons chorea with lithium carbonate.
A double-blind trial. Lancet 1(7848),
107109 (1974).
84 Fasano A, Mazzone P, Piano C,
QuarantaD, Soleti F, Bentivoglio AR.
GPi-DBS in Huntingtons disease: results on
motor function and cognition in a
72year-old case. Mov. Disord. 23(9),
12891292 (2008).
85 Hebb MO, Garcia R, Gaudet P, MendezIM.
Bilateral stimulation of the globus pallidus
internus to treat choreathetosis in
Huntingtons disease: technical case report.
Neurosurgery 58(2), E383 (2006).
86 Moro E, Lang AE, Strafella AP etal.
Bilateral globus pallidus stimulation for
Huntingtons disease. Ann. Neurol. 56(2),
290294 (2004).
87 Biolsi B, Cif L, Fertit HE etal. Long-term
follow-up of Huntington disease treated by
bilateral deep brain stimulation of the internal
globus pallidus. J. Neurosurg. 109(1),
130132 (2008).
88 Madrazo I, Franco-Bourland RE,
CastrejonH, Cuevas C, Ostrosky-Solis F.
Fetal striatal homotransplantation for
Huntingtons disease: first two case reports.
Neurol. Res. 17(4), 312315 (1995).
89 Philpott LM, Kopyov OV, Lee AJ etal.
Neuropsychological functioning following
fetal striatal transplantation in Huntingtons
chorea: three case presentations. Cell
Transplant 6(3), 203212 (1997).
90 Kopyov OV, Jacques S, Lieberman A,
DumaCM, Eagle KS. Safety of intrastriatal
neurotransplantation for Huntingtons
disease patients. Exp. Neurol. 149(1), 97108
(1998).
91 Bachoud-Levi AC, Gaura V, Brugieres P
etal. Effect of fetal neural transplants in
patients with Huntingtons disease 6years
after surgery: a long-term follow-up study.
Lancet. Neurol. 5(4), 303309 (2006).
92 Trial watch. NeuroSearchs dopaminergic
stabilizer improves movement disorders in
Huntingtons disease. Nat. Rev. Drug Discov.
9(4), 260 (2010).
future science group
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