Chorea

Chorea REVIEW ARTICLE

By Erin Furr Stimming, MD, FAAN; Danny Bega, MD C O N T I N U UM A U D I O
I NT E R V I E W A V A I L AB L E
ONLINE
ABSTRACT 
VIDEO CONTENT
PURPOSE OF REVIEW: Thisarticle provides an overview of the diagnostic and A V AI L A B L E O N L I N E
therapeutic approach to a patient with chorea. The phenomenology of
chorea is described in addition to other common hyperkinetic movements CITE AS:
that may be mistaken for or coexist with chorea. Chorea can be acquired or CONTINUUM (MINNEAP MINN)
hereditary. Key historical and clinical features that can aid in determining 2022;28(5, MOVEMENT DISORDERS):
1379–1408.
the etiology are reviewed, and pharmacologic and nonpharmacologic
treatment strategies are discussed. Address correspondence to
Dr Erin Furr Stimming, 6431
Fannin St, MSB 7.004, Houston,
RECENT FINDINGS: Clinical investigations are under way to target transcription
TX 77030, erin.e.furr@uth.tmc.
and translation of the mutant huntingtin protein as a potential disease- edu.
modifying strategy in Huntington disease (HD). Additional heritable factors
RELATIONSHIP DISCLOSURE :
have been revealed through genome-wide association studies. Symptom- Dr Furr Stimming has received
focused treatments for HD are are being studied, including a third vesicular personal compensation in the
monoamine transporter-2 (VMAT2) inhibitor for chorea attenuation and range of $500 to $4999 for
serving as a consultant for Teva
drugs to target irritability and cognitive impairment. Increased availability Pharmaceutical Industries Ltd
of genetic testing has led to increased awareness of HD mimics (eg, and Wave Life Sciences, on a
C9orf72 and IgLON5). scientific advisory board for
Amneal Pharmaceuticals LLC,
and on speakers bureaus for
SUMMARY: Chorea is a relatively common hyperkinetic disorder with a broad Sunovion Pharmaceuticals Inc
and Teva Pharmaceutical
differential. The first step in the approach to a patient with chorea is accurately Industries Ltd. Dr Furr Stimming
defining the phenomenology. Once it has been determined that the patient has served as an editor and
has chorea, the investigation into determining an etiology can begin. Factors author for McGraw Hill and
Oxford University Press. The
such as age of onset, time course, family history, unique clinical features, and institution of Dr Furr Stimming
imaging and laboratory findings can guide the diagnosis. Treatments for most has received research support
causes of chorea are purely symptomatic, although it is important to recognize from the CHDI Foundation;
Cures Within Reach; Huntington
causes that are reversible or have disease-modifying interventions. Study Group/Neurocrine
Biosciences, Inc; the
Continued on page 1408
INTRODUCTION
C
UNLABELED USE OF
horea is a hyperkinetic movement disorder that derives its name PRODUCTS/INVESTIGATIONAL
from choreia, a Greek term for dance. Using the term chorea in USE DISCLOSURE :
medicine dates back to the Middle Ages when Chorea Sancti Viti, or Drs Furr Stimming and Bega
discuss the unlabeled/
dancing mania, occurred during the black plague epidemics. investigational use of
Although it is not clear whether this was mass functional neurologic amantadine, benzodiazepines,
botulinum toxin injections,
disorder or a temporal coincidence, the terminology was coined in this era and
cannabinoids, carbamazepine,
later used by Thomas Sydenham to describe a specific type of chorea.1 clozapine, deep brain
In modern-day neurology, chorea refers to involuntary random, irregular, stimulation, olanzapine,
quietipine, risperidone, and
purposeless movements that flow from one body part to the next. The valbenazine for the treatment of
unpredictable fragmented movements may involve the limbs, trunk, neck, face, Huntington disease and other
and tongue. The velocity of chorea can vary from fast (which may make it causes of chorea.
difficult to differentiate from myoclonus) to slow (which may make it difficult © 2022 American Academy
to differentiate from dystonia). The intensity, frequency, and amplitude of of Neurology.
CONTINUUMJOURNAL.COM 1379
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

CHOREA
chorea may vary from subtle low-amplitude movements of varying frequency

in the upper face to severe large-amplitude movements in the limbs and trunk.2-4
Chorea may initially manifest as fidgeting and go unnoticed or denied by
patients, despite usually being detectable by others. Some patients disguise
chorea by incorporating it into a voluntary movement. Motor impersistence is
another common associated feature of chorea (independent of the etiology) and
is demonstrated by the inability to maintain a grasp on the examiner’s hand
(ie, milkmaid’s grip) or sustain tongue protrusion.2,5
CHOREA VERSUS OTHER HYPERKINETIC MOVEMENTS

Differentiating chorea from other hyperkinetic movements can be challenging,
especially when various movements coexist. Recognizing the phenomenology of
the movements observed can direct the diagnostic approach and treatment strategy.
Dystonia
Dystonia is defined by sustained muscle contractions and abnormal postures that
are repetitive, patterned, twisting, and sometimes tremulous. Compared to
chorea, dystonic movements are generally slower. Dystonia may occur at rest;
however, it is typically triggered by voluntary actions. Unique features of
dystonia include an alleviating maneuver (previously described as a sensory
trick), a null point, and mirror movements.6,7 Of note, dystonic movements can
coexist with chorea.
Dyskinesia
Dyskinesia is a general term for abnormal movements, one of which is chorea.
The term is most frequently used for specific medication-induced hyperkinetic
conditions, such as levodopa-induced dyskinesia in Parkinson disease (PD) or
tardive dyskinesia induced by neuroleptic medications.8 Chorea and
choreoathetoid movements are the most common forms of levodopa-induced
dyskinesia9; however, dyskinesia is not synonymous with chorea.
Myoclonus
Myoclonus is a brief lightninglike jerk that is usually described as the quickest
movement a body part can produce, ranging from approximately 50 to 200
milliseconds.10 This movement disorder can be caused by muscle contraction
(positive myoclonus) or sudden interruption of muscle activity (negative
myoclonus). Asterixis, which often appears in metabolic encephalopathies, is a
form of negative myoclonus. Chorea also has fast movement fragments, but,
unlike in myoclonus, the movements occur together with slower movements to
produce a flowing quality.10,11
Tremor
Rhythmicity, oscillation, and predictability are important factors that distinguish
tremor from chorea. Tremors are generally classified by their location, the
posture in which they occur, amplitude, and frequency. Tremors may
accompany other movement disorders, such as dystonia.12
Tics
Tics are nonrhythmic, recurrent, patterned movements or vocalizations usually
associated with a premonitory urge and some degree of suppressibility. Tics may
1380 OCTOBER 2022

be simple or complex and can vary in type, severity, and anatomic location. The KEY POINTS
repetitiveness, accompanying urge, and suppressibility of tics differentiate them
● Chorea refers to random,
from chorea.13-15 irregular, purposeless
movements that flow from
Ballism one body part to the next.
Ballism, or ballismus, is a high-amplitude movement that usually involves
● Chorea is generalized in
proximal parts of the limbs (ie, shoulder or hip), often described as a flinging or
many patients; however, its
kicking movement.16 localized distribution may
act as an important
Athetosis diagnostic factor to
Athetosis is of lower amplitude than chorea and often distal, although it may determine the underlying
etiology. For example,
involve the trunk. It is a writhing movement with slow continuous flow rather forehead involvement is
than the fragmented sequence seen in chorea.17,18 Chorea may coexist more common in Huntington
with athetosis. disease. Orobuccolingual
chorea is more common in
tardive syndromes.
EVALUATING CHOREA
In addition to associated neurologic signs, the location or distribution of chorea
can be an important clue when narrowing the differential diagnosis.
Body Distribution
Chorea is generalized in many cases; however, its localized distribution may
act as an important diagnostic factor to determine the underlying etiology
(FIGURE 8-1).19,20
HEMICHOREA. Hemichorea has been classically associated with focal vascular

lesions of the contralateral subthalamic nucleus or basal ganglia. However,
vascular lesions in other territories, such as the thalamus or temporoparietal
cortex, have also been implicated in causing chorea.21 Other etiologies that
may cause hemichorea with focal lesions are nonketotic hyperglycemia and
opportunistic infections in the setting of human immunodeficiency virus
FIGURE 8-1
Distribution of chorea and potential causes.

CHOREA
(HIV) and acquired immunodeficiency syndrome (AIDS).16,22,23 Some

conditions may cause hemichorea in the absence of an apparent brain lesion.
Examples include autoimmune chorea (eg, Sydenham chorea), paraneoplastic
syndromes, and variant Creutzfeldt-Jakob disease.24,25 However, these
conditions may also present as generalized chorea.
OROBUCCOLINGUAL CHOREA. Orobuccolingual chorea may present in several

conditions, with the most common being tardive syndromes.8 Involvement of
the orobuccolingual muscles may occur in paraneoplastic syndromes (eg,
N-methyl-D-aspartate [NMDA] receptor encephalitis), polycythemia vera,
and chorea-acanthocytosis.25-27 In chorea-acanthocytosis, chorea is frequently
accompanied by oromandibular and lingual dystonia, leading to tongue
protrusion and feeding dystonia.19,28 Other etiologies of chorea may present
with oromandibular dystonia. Some examples are Lesch-Nyhan syndrome,
Lubag disease (X-linked dystonia-parkinsonism), Wilson disease, and
pantothenate kinase–associated neurodegeneration (PKAN).29-32
FACIAL OR FOREHEAD CHOREA. Chorea involving the forehead/upper face,

manifested by frontalis contraction, intermittently widened palpebral
fissures, and irregular blinking, is common in Huntington disease (HD). This
is not a pathognomonic feature of HD but is far less common in tardive
syndromes and can therefore help when seen in addition to delayed ocular
saccade initiation and velocity or other features common in HD.
Evaluation
Observation throughout the encounter is of utmost importance when evaluating
an individual with chorea. Multiple scales are available to rate chorea severity;
however, if a rating scale is not used, describing the location and severity of the
chorea is sufficient. One of the most widely recognized validated scales is the
Unified Huntington’s Disease Rating Scale (UHDRS), in which the total maximal
chorea score within the motor section of the scale is used to measure the severity
of chorea ranging from absent to severe. The chorea is rated in seven body
regions: the face, orobuccolingual, trunk, and each limb independently.33 The
Abnormal Involuntary Movement Scale (AIMS) is another commonly used scale
to evaluate chorea in the setting of tardive dyskinesia and assess chorea severity
in various locations.34
When evaluating chorea, the entire body should be visible, including the feet
(without socks), with the patient sitting on an examination table. It is imperative
to evaluate the chorea throughout the encounter, as the severity can fluctuate
with distraction.33 Like most hyperkinetic movements, the severity may increase
with heightened emotion. Observing gait (more specifically, tandem gait) can
illuminate the severity of the chorea.
Although mild chorea may go unnoticed by patients and their caregivers,
moderate chorea is typically more apparent. In HD, anosognosia is common;
therefore, individuals may be unaware of even severe chorea. Chorea usually
affects the limbs, trunk, and face. Less frequently, it can interfere with
respiration and phonation, presenting with slurred speech or involuntary
vocalizations (eg, grunting, humming). Chorea usually presents at rest,
disappears during sleep, and may increase with distracting maneuvers such as
counting backward. Chorea may be partially suppressible or camouflaged by
1382 OCTOBER 2022

the patient. Motor impersistence, as mentioned above, is a common KEY POINTS
phenomenon in individuals with chorea. This can be demonstrated by asking the
● Because the differential
patient to squeeze the examiner’s finger or sustain tongue protrusion for diagnosis for chorea is
10 seconds.35,36 broad, it is generally helpful
to begin by categorizing
PATHOPHYSIOLOGY chorea as (1) inherited versus
acquired and (2) childhood
The pathophysiology of chorea is linked to the neural network connecting the
onset versus adult onset.
thalamus to the basal ganglia, including the striatum, globus pallidus externus,
and globus pallidus internus as well as related nuclei (eg, the subthalamic nucleus ● Clues to differentiate
and substantia nigra). The classic model of basal ganglia function describes the inherited choreas from
direct and indirect pathways that originate from striatal medium spiny neurons. acquired choreas include
the timeline (acute,
According to this model, a cortical impulse activates medium spiny neurons subacute, or chronic
with the release of glutamate. Medium spiny neurons control downstream [>1 year]) and course (static,
pathways with γ-aminobutyric acid (GABA), a naturally inhibitory signal. In the paroxysmal, or progressive).
direct pathway, the inhibition of the globus pallidus internus, which is also
γ-aminobutyric acid–mediated (GABAergic), results in disinhibition of the
thalamus and locomotor activation. Conversely, the indirect pathway activates
the globus pallidus internus with inhibition of the excitatory subthalamic nucleus
and ultimately reduces locomotion. In addition to the cortical impulses, the
substantia nigra pars compacta controls medium spiny neurons and downstream
pathways by releasing dopamine. Although chorea has different etiologies, many
of its various forms can be explained by decreased inhibitory input of the globus
pallidus internus to the thalamus, resulting in facilitation of thalamocortical
motor drive.23,37
However, some discrepancies exist. For example, internal pallidal ablation
(globus pallidus internus pallidotomy) has been successfully used in treating
some forms of chorea, whereas according to the classic model, it should actually
increase thalamocortical motor drive and worsen chorea. In another example,
findings on positron emission tomography (PET) have shown evidence of striatal
hypometabolism in HD and some other causes of chorea, which correlates with
neuronal loss. Conversely, in patients with hyperthyroidism, polycythemia vera,
and Sydenham chorea, hypermetabolism of the striatum was found. These
inconsistencies suggest a more complex mechanism and even different
pathophysiology among variants of chorea.23,38
APPROACH TO THE DIAGNOSIS OF CHOREA

The differential diagnosis for chorea is broad, but it is generally helpful to begin
by categorizing chorea as (1) inherited versus acquired and (2) childhood onset
versus adult onset. Many algorithms have been published to help work through
the differential diagnosis of chorea, and these general categories serve as
guidelines.16,23,39,40 When assessing chorea, a careful family history should
always be elicited, although the absence of a family history should not be relied
on as an exclusion for a hereditary etiology.
Among acquired choreas, causes include postinfectious, autoimmune,
drug-induced, vascular, and metabolic abnormalities; however, the emphasis is
typically on identifying potentially treatable or reversible conditions.41
Additional features that aid in the differential diagnosis discussed in this article
include time course (acute, subacute, or chronic [>1 year] and static, paroxysmal,
or progressive), comorbid history and examination features, and comorbid
imaging or laboratory features.

CHOREA
Hereditary Choreas
HD is the most common cause of adult-onset hereditary chorea, but even in
HD, 5% of cases represent a de novo HTT pathogenic variant or expansions in
the nonpathogenic but mutable range (ie, CAG repeats may expand in
successive generations into the pathogenic range), and family history may be
incomplete, incorrect, or unknown.42 Among other hereditary causes, some
share phenotypic characteristics with HD and are considered HD mimics or
phenocopies and others have different inheritance patterns and unique
features that may lead to their consideration, but all are considered rarer than
HD and therefore considered only after a negative test for the HTT
pathogenic variant.
HUNTINGTON DISEASE. HD is the most common cause of adult-onset hereditary

chorea (VIDEO 8-1 and VIDEO 8-2), affecting approximately 5 per 100,000 to 12
per 100,000 people.43 It is caused by an autosomal dominant trinucleotide
repeat expansion (CAG) in the huntingtin gene (HTT) on chromosome 4p16.3.
Repeat lengths of 40 and above have full penetrance, with a phenotype
consisting of progressive motor, cognitive, and behavioral changes. The precise
mechanism for the degenerative changes in HD is unclear, but mutant
huntingtin protein forms nuclear aggregates in the striatum, particularly leading
to loss of medium spiny neurons. A CAG repeat length of 26 or lower is
considered normal (TABLE 8-144). Individuals who have 36 to 39 CAG repeats are
considered to have reduced penetrance but can still develop the disease. In those
with 27 to 35 CAG repeats, the phenomenon of “anticipation” via paternal
inheritance can pose risk for expansion into the HD range in the next generation.
Although HD symptom onset can occur at any age, the average age of onset
is in the third or fourth decade of life, and the average lifespan is approximately
15 to 20 years after symptom onset. The age of motor onset is inversely correlated
with the number of CAG repeats; however, this only accounts for approximately
50% to 70% of the variance.45 Through genome-wide association studies
evaluating large cohorts, the Genetic Modifiers of Huntington’s Disease
(GeM-HD) Consortium has identified genes involved in DNA maintenance and
repair that have been implicated in modifying motor symptom onset by likely
influencing somatic expansion of the HTT CAG repeat.46,47 The GeM-HD
Consortium and others determined that the uninterrupted CAG repeat length
TABLE 8-1 CAG Repeats in Huntington Diseasea
Risk to
CAG repeat count Classification Disease status offspring
<26 Normal Will not be affected None
27-35 Intermediate Will not be affected? (case reports of symptomatic individuals) Increased
36-39 Reduced penetrance May or may not be affected 50%
40+ Full penetrance Will be affected 50%
a
Data from Nance MA, et al.44
1384 OCTOBER 2022

is more influential in contributing to the age of motor onset than the KEY POINTS
polyglutamine length.47
● Huntington disease is the
Prodromal HD can occur approximately 10 years before a clinical most common cause of
diagnosis.46 During this period, subtle motor and nonmotor symptoms maybe adult-onset hereditary
be present but are not significant enough to warrant a clinical diagnosis. chorea. It is imperative that
A clinical diagnosis of HD has historically been based on motor symptoms. genetic counseling occur
before testing.
However, cognitive and behavioral symptoms can be deleterious and may
precede significant motor symptoms. Reilmann and colleagues48 proposed a ● Huntington disease
revision of the diagnostic criteria to include nonmotor features, more mimics or phenocopies
specifically cognitive symptoms, when making a diagnosis. Subsequently, a include several inherited
Movement Disorder Society task force proposed a refinement of the clinical rare degenerative
conditions and may be
diagnostic criteria.49,50 Efforts are under way to expand upon this for both associated with the triad of
clinical and research purposes. chorea, dementia, and
Juvenile HD (also known as the Westphal variant) occurs before the age of 20 behavioral disturbances.
and is associated with CAG repeat lengths higher than 55; it phenotypically can
present with akinesia, parkinsonism, and seizures rather than chorea. Although
chorea is the most common and prototypical movement disorder associated with
HD, especially among those with onset in middle age or older adult life, other
movements often seen include ataxia, dystonia, parkinsonism, tics, dysarthria,
dysphagia, and impaired ocular saccade initiation and velocity.43 In fact, delayed
ocular saccade initiation can be a helpful clue when trying to differentiate HD
from other causes of chorea.43
Cognitive decline eventually occurs in all individuals with HD. Executive
dysfunction is common, including impairments in planning, working memory,
and attention. The cognitive symptoms are progressive and lead to functional
decline and dependence. Behavioral features are variable among individuals with
HD. Depression, irritability, anxiety, and impulsivity are among the most
common psychiatric symptoms and can contribute to the high suicide rate in this
population. Obsessive-compulsive symptoms and apathy are not uncommon,
and, unlike other neuropsychiatric features, apathy longitudinally worsens over
time. Psychosis can also be seen, albeit rarely.49,51
HUNTINGTON DISEASE MIMICS/PHENOCOPIES. Hereditary conditions that mimic

HD should be considered whenever testing for the pathogenic variant does
not reveal an expansion in the HTT gene. These conditions make up 1% to
7% of HD-negative genetic choreas.16,23,52 The shared phenotype is a
hereditary progressive neuropsychiatric condition involving chorea, cognitive
impairment, and psychiatric or behavioral abnormalities. Unfortunately,
the cause of HD phenocopies remains undetermined in the majority of those
with a negative gene test.53
HUNTINGTON DISEASE–LIKE DISORDERS. Four genes associated with Huntington

disease–like (HDL) syndromes have been described. HDL2 is a rare autosomal
dominant pathogenic variant in the gene encoding junctophilin-3 (JPH3). Like
HD, it is associated with a CAG trinucleotide repeat expansion. It resembles HD
and has primarily been reported in individuals of African descent. HDL1 is
caused by a pathogenic variant in the prion protein gene ( PRNP) and can mimic
HD; however, acquired prion diseases such as Creutzfeldt-Jakob disease can also
be associated with chorea. HDL3 is exceedingly rare and is associated with
ferritin-associated basal ganglia disease.54 HDL4 is also known as spinocerebellar

CHOREA
ataxia type 17 (SCA17) and is discussed in the section on spinocerebellar ataxia

type 17 and other hereditary ataxias.
DENTATORUBRAL PALLIDOLUYSIAN ATROPHY. Similar to HD, dentatorubral

pallidoluysian atrophy (DRPLA) is inherited via an autosomal dominant pattern
with a trinucleotide CAG expansion. The pathogenic variant in DRPLA is in the
atrophin-1 gene (ATN1) on chromosome 12p13. Although very rare, DRPLA has
a higher prevalence in individuals of Japanese ancestry, in which the prevalence
is 0.2 per 100,000 to 0.4 per 100,000 people.55 Cases have also been described in
the Haw River Valley region of North Carolina.56 The clinical phenotype is
similar to HD, although epilepsy may also be seen. MRIs of individuals with
DRPLA show characteristic white matter changes and atrophy in regions
indicated in the name of the disorder: the dentate, red nucleus, and pallidum.
C9ORF72. Expanded hexanucleotide repeat pathogenic variants in the C9orf72

gene have increasingly been associated with various neurologic conditions, in
particular motor neuron disease and frontotemporal dementia. In fact, the
pathogenic variant is one of the most common genetic causes of amyotrophic
lateral sclerosis and frontotemporal lobar degeneration in some populations. The
gene is thought to have a role in membrane trafficking, which may be relevant to
various neurologic conditions. The expression can vary even among individuals
in the same family. Although chorea is a rare manifestation of this pathogenic
variant, it is now recognized among the most common phenocopies of HD,
particularly among a UK-based cohort.52
SPINOCEREBELLAR ATAXIA TYPE 17 AND OTHER HEREDITARY ATAXIAS. Many primary

chorea syndromes such as HD can have ataxia as a comorbid feature, and,
likewise, many primary ataxia disorders can have chorea as a feature. Hereditary
ataxias have heterogeneous inheritance patterns, although many, such as SCA17,
are autosomal dominant. In most cases, cerebellar atrophy is apparent on MRI.
Among the autosomal dominant forms of hereditary ataxia, SCA17 can affect
White and Asian populations and can have a phenotype that mimics HD, with
neuropsychiatric features and hyperkinetic movements; it has therefore also
been termed HDL4. Like HD, SCA17 is a trinucleotide CAG repeat expansion
disorder. In this case, the pathogenic variant is in TBP on chromosome 6q27.57
Other SCAs can also have phenotypes that overlap with HD. SCA3 is among the
most common autosomal dominant spinocerebellar ataxias and can also cause
chorea. Autosomal recessive ataxias that cause chorea include Friedreich ataxia,
ataxia telangiectasia, and ataxia with oculomotor apraxia types 1 and 2.
OTHER HEREDITARY CHOREAS. Inheritance patterns for hereditary causes of

chorea can also include autosomal recessive and X-linked disorders.
NEUROACANTHOCYTOSIS. Neuroacanthocytosis refers to a group of extremely rare

disorders with the characteristic feature of acanthocytes (spiculated, abnormally
shaped red blood cells) found on peripheral blood smear. Chorea-acanthocytosis
is a rare autosomal recessive cause of chorea seen in 1 per 1 million to 3 per
1 million individuals.58 Although generalized chorea is seen, movement in the
orofacial and orobuccolingual regions is characteristically predominant. This can
lead to self-injurious mutilation of the orobuccolingual region as well as
1386 OCTOBER 2022

prominent hypersalivation and dysphagia with lingual dystonia. Acanthocytes KEY POINTS
are characteristically seen on peripheral blood smear, although both false
● Pathogenic variants in
positives and false negatives can occur. Chorea-acanthocytosis is caused by a ATN1 dentatorubral
pathogenic variant in the VPS13A gene, which encodes for the protein chorein. pallidoluysian atrophy are
An X-linked form of the disease is known as McLeod syndrome and is associated associated with
with comorbid neuropathy and cardiomyopathy. HDL2 and the syndrome of characteristic MRI changes
in the dentate, red nucleus,
brain iron accumulation may also be causes of neuroacanthocytosis. and pallidum.
HEREDITARY DISORDERS ASSOCIATED WITH BASAL GANGLIA MINERALIZATION. ● Pathogenic variants in

Hereditary forms of chorea can result from abnormal mineral accumulation in C9orf72 can mimic
Huntington disease, but
the basal ganglia. This includes iron (neurodegeneration with brain iron
variable expression may also
accumulation [NBIA] disorders), calcium (Fahr disease), and copper (Wilson include amyotrophic lateral
disease), each of which may have corresponding MRI abnormalities. sclerosis and
frontotemporal dementia.
NEURODEGENERATION WITH BRAIN IRON ACCUMULATION. NBIA disorders are a
● Pathogenic variants in
heterogeneous group of disorders in which iron accumulates in the basal ganglia, VPS13A cause chorea-
leading to various movement disorders. Some of these disorders are related to acanthocytosis, with
genes directly involved in iron metabolism, whereas others are related to genes characteristic
involved in lysosomal or autophagy pathways.59 MRI of the brain is invariably orobuccolingual chorea and
acanthocytes on blood
abnormal in these conditions and can have characteristic patterns of iron
smear. McLeod syndrome is
accumulation in each condition. As a group, NBIA disorders vary in age of onset an X-linked form.
and inheritance patterns. NBIA disorders occur in 1 per 500,000 people, with
about half of these cases being PKAN. PKAN is an autosomal recessive disorder ● Chorea can result from
caused by a pathogenic variant in the pantothenate kinase 2 gene ( PANK2) and abnormal mineral
accumulation in the basal
can present from early childhood to midadulthood. It has a characteristic pattern ganglia. This includes iron
of signal change in the basal ganglia on MRI known as the eye of the tiger sign.60 (neurodegeneration with
PKAN is also described as a neuroacanthocytosis syndrome. Adult-onset NBIA brain iron accumulation),
disorders include the rare conditions of aceruloplasminemia and calcium (Fahr disease), and
copper (Wilson disease),
neuroferritinopathy. Aceruloplasminemia is caused by a recessive pathogenic each of which may have
variant in the CP gene encoding ceruloplasmin, whereas neuroferritinopathy is corresponding MRI
caused by a dominant pathogenic variant in the gene for ferritin light abnormalities.
chain (FTL).
BASAL GANGLIA CALCIFICATIONS/FAHR DISEASE. Minor calcifications in the basal

ganglia are not uncommon on imaging, but more significant accumulations can
lead to movement disorders. Parkinsonism and tremor are the most common
movement disorders that arise from basal ganglia calcifications, but chorea can
also be seen. The calcification will often show up prominently on head CT,
involving cerebellar and brainstem structures in addition to the basal ganglia.
The inheritance pattern is often autosomal dominant, although different genes
have been implicated, including SLC20A2 and XPR1. Secondary causes of basal
ganglia calcifications may include endocrine abnormalities such as
hypoparathyroidism, TORCH infections (toxoplasmosis, other infections,
rubella, cytomegalovirus infection, and herpes simplex), and certain toxic
exposures (eg, carbon monoxide).61
WILSON DISEASE. Wilson disease is an autosomal recessive genetic disorder that

results from pathogenic variants in the gene encoding the ATP7B protein.
ATP7B is a P-type ATPase that mediates ATP-dependent transport of copper.
ATP7B is highly expressed in hepatocytes, where it has dual roles in copper

CHOREA
CASE 8-1 A 34-year-old right-handed woman presented to the clinic for

involuntary movements. The patient had been “fidgety” since childhood
but never thought much about it until her primary care physician
recommended she see a neurologist. Her father had similar movements,
as did her 12-year-old daughter, who was delayed in meeting her motor
milestones. The patient denied any significant past medical history
except for hypothyroidism (for which she was taking levothyroxine) and
asthma, although she did not have additional details about her diagnosis.
She endorsed mild anxiety but denied any other significant psychiatric
symptoms.
Neurologic examination revealed involuntary, arrhythmic, low- to
moderate-amplitude movements in the extremities and trunk consistent
with choreoathetoid movements in addition to intermittent bilateral
upper extremity myoclonus (VIDEO 8-3). Her tone was normal throughout,
she had normal saccade initiation and velocity, and tongue protrusion
was sustained for 9 seconds. Gait revealed a slightly wide base, normal
stride, impaired tandem gait with bilateral upper extremity dystonic
posturing, and distal upper extremity chorea.
Brain MRI and laboratory studies were normal. Genetic testing (HTT
test) previously performed by her primary care physician had not
revealed a pathogenic CAG expansion on either allele. Additional genetic
testing revealed a pathogenic variant in the NKX2-1 gene. A diagnosis of
benign hereditary chorea was made. Treatment was initiated with a
vesicular monoamine transporter-2 (VMAT2) inhibitor, and the patient
was counseled about the importance of preventive cancer screening.
COMMENT In this patient, clues to the diagnosis of benign hereditary chorea included
a family history suggesting an autosomal dominant inheritance pattern,
normal brain MRI, hypothyroidism, and respiratory symptoms. In addition,
childhood onset of chorea would be atypical for juvenile-onset Huntington
disease as the phenotype is typically hypokinetic. The clinical features of
NKX2-1 benign hereditary chorea have become more clearly delineated
with increased reporting of cases caused by various pathogenic variants
within this gene, highlighting hypotonia, motor developmental delay,
chorea, hypothyroidism, and recurrent respiratory tract infections as the
core features of brain-lung-thyroid syndrome. Treatment is symptomatic,
and multiple medications have been reported as being effective, including
carbidopa/levodopa. Additional neurologic findings may include
myoclonus, tremor, dystonia, and cognitive deficits, which brings into
question the terminology currently used to describe this syndrome. A
renaming to NKX2-1–related disorder has recently been proposed.64
1388 OCTOBER 2022

metabolism. First, ATP7B facilitates incorporation of copper into ceruloplasmin, KEY POINT
which is then secreted into the bloodstream. Second, ATP7B promotes the biliary
● Mutations in ADCY5 are
excretion of copper by sequestering copper into vesicles that are excreted into bile associated with childhood
via exocytosis. Pathogenic variants in ATP7B lead to impaired copper excretion, hypotonia. The chorea that
resulting in copper accumulation in hepatocytes with resultant hepatotoxicity and may develop worsens with
accumulation of excess copper in other organs, including the brain. Neurologic sleep deprivation.
symptoms can be the presenting manifestation in about 18% to 68% of patients.
Anyone younger than 50 years of age with unexplained neurologic or hepatic
findings should be considered for screening for Wilson disease using serum
ceruloplasmin, 24-hour urine copper, and slit-lamp eye examination for
Kayser-Fleisher rings. Neurologic symptoms are broad, but common
manifestations include dysarthria, dystonia, tremor, ataxia, chorea, and
parkinsonism. MRI of the brain in patients with Wilson disease commonly reveals
changes within the bilateral basal ganglia as well as the thalami and brainstem on
T1- or T2-weighted sequences. Hyperintense T2 signal in the midbrain surrounding
the red nuclei in this condition has been dubbed the face of the giant panda sign.62
Nonwilsonian causes of liver failure with portosystemic shunting can cause an
acquired hepatolenticular degeneration due to deposition of other minerals and
toxins, such as manganese, in the basal ganglia. Similar to copper deposition,
these minerals can have a hyperintense T1 signal in the basal ganglia on MRI.
BENIGN HEREDITARY CHOREA. Familial forms of chorea that have an onset in

childhood and remain fairly stable or only mildly progressive are suggestive of
benign hereditary chorea. Although many cases are truly benign, some are
associated with increased risk of malignancy and with pulmonary or thyroid
disorders—a triad known as the brain-lung-thyroid disease—depending on the
severity of the pathogenic variant in the thyroid transcription factor 1 gene
(TITF1/NKX2-1). The pattern of inheritance is typically autosomal dominant.
In the first few years of life, some individuals with benign hereditary chorea
will experience hypotonia and some delay in motor milestones, but it is
generally stable after the first decade of life. Unlike other forms of hereditary
chorea, cognitive decline is less common (CASE 8-1).63
ADCY5-RELATED CHOREA. Adenylyl cyclase 5 (ADCY5) mutation-related

disorders are typically associated with childhood hypotonia and
developmental delay. However, chorea (particularly of the orobuccolingual
area) that fluctuates in severity (particularly worsening with drowsiness and
sleep deprivation) has been described. The gene is involved in the synthesis of
a cyclic adenosine monophosphate (cAMP) second messenger involved in
intracellular processes of medium spiny neurons. The inheritance can occur in
an autosomal dominant pattern or occur as a de novo pathogenic variant.65
PAROXYSMAL KINESIGENIC AND NONKINESIGENIC DYSKINESIA. Paroxysmal

kinesigenic dyskinesia and paroxysmal nonkinesigenic dyskinesia are
hereditary paroxysmal or episodic movement disorders that occur in
childhood and are most commonly associated with chorea or dystonia. Unlike
other conditions described here, individuals typically have a normal
neurologic examination between episodes, and the disorders can often be
confused with functional movement disorders. In paroxysmal kinesigenic
dyskinesia (also known as DYT10), episodes typically last seconds to minutes

CHOREA
and can occur countless times per day. Episodes are triggered by movement, but
individuals will often describe a prodromal sensation before an episode. The
choreiform movements can affect any body region but are often asymmetric,
and they typically respond well to carbamazepine. In paroxysmal nonkinesigenic
dyskinesia (also known as DYT8), episodes are typically longer, lasting minutes
to hours. Episodes are also less frequent than in paroxysmal kinesigenic
dyskinesia and are not triggered by movement but rather by stress, extremes of
temperature, alcohol, or excitement. Paroxysmal nonkinesigenic dyskinesia is
less responsive to pharmacotherapy than paroxysmal kinesigenic dyskinesia.
Paroxysmal kinesigenic dyskinesia is associated with autosomal dominant
pathogenic variants in the proline-rich transmembrane protein 2 gene ( PRRT2);
the same gene has been associated with other conditions such as hemiplegic
migraine and episodic ataxia. Paroxysmal nonkinesigenic dyskinesia is also an
autosomal dominant disorder, due to a pathogenic variant in the
myofibrillogenesis regulator 1 gene (MR-1). Another related condition,
paroxysmal exercise-induced chorea, is associated with a deficiency in the
glucose-transporter 1 (GLUT-1).66
Acquired/Secondary Choreas
Etiologies of acquired choreas include postinfectious, autoimmune,
drug-induced, vascular, and metabolic abnormalities. The workup emphasizes
ruling out potentially treatable or reversible conditions first. Additional features
to pay attention to include time course, comorbid history, examination features,
and imaging or laboratory features.
SYDENHAM CHOREA. Sydenham (or poststreptococcal) chorea is the most

common cause of chorea in childhood (VIDEO 8-4). Onset is typically acute or
subacute in children after an infection with group A streptococci and is
thought to result from antibodies produced against the bacteria that bind to
basal ganglia neurons. Confirmation of group A streptococci infection on
throat culture, positive antistreptolysin O or antideoxyribonuclease (DNAse)
antibodies, or carditis may support the diagnosis. However, because of the
variable lag from infection to onset of symptoms, antistreptolysin O titers and
antibodies can have false negatives, and a diagnosis is typically made clinically.66
Chorea and athetosis in the body and hands are common, but additional findings
may include ticlike behaviors, irritability, and impairments in attention.
Symptoms often naturally self-resolve over months, although in rare cases may
persist or recur. Recurrence occurring in pregnancy, typically in the first
trimester, is known as chorea gravidarum.
SYSTEMIC LUPUS ERYTHEMATOSUS AND OTHER AUTOIMMUNE-RELATED CHOREAS.

Chorea is a rare manifestation of systemic lupus erythematosus (SLE) but
rarely (1% to 4% of cases of systemic lupus erythematosus) may be seen as a
presenting manifestation of the disease.40 This may be related to circulating
antiphospholipid and anticardiolipin antibodies, although vascular
phenomena have also been proposed. Behçet disease, Sjögren syndrome, and
celiac disease are all systemic autoimmune conditions with antibodies that can
be rarely associated with chorea. Anti-NMDA receptor encephalitis is a known
cause of autoimmune encephalitis. Like other forms of limbic encephalitis, it
can be associated with epilepsy and behavioral changes. Other
1390 OCTOBER 2022

neurobehavioral features, including chorea and catatonia, are seen commonly KEY POINTS
with NMDA receptor encephalitis. In some patients, particularly in young
● Paroxysmal disorders of
women, NMDA receptor antibodies can be paraneoplastic related to ovarian chorea have characteristic
teratomas. Immunoglobulinlike cell adhesion molecule 5 (IgLON5) is an triggers. Paroxysmal
antibody that has been discovered recently in association with parasomnias nonkinesigenic dyskinesia is
but can be associated with cognitive impairment, gaze palsies, and chorea.40 triggered by stress,
extremes of temperature,
alcohol, or excitement.
PARANEOPLASTIC CHOREA. Paraneoplastic causes of chorea should be Paroxysmal kinesigenic
considered in adults, particularly when the onset is subacute and associated dyskinesia episodes are
with other systemic findings such as weight loss. Chorea often develops before shorter and more frequent
and triggered by movement.
tumor diagnosis, and early recognition may lead to detection of occult
malignancies. Antibodies to nuclear and cytoplasmic antigens, such as anti-Hu ● Sydenham chorea is the
and anti–collapsin response mediator protein 5 (CRMP-5) antibodies, most common cause of
associated with small cell lung cancer are among the most common to cause chorea in childhood.
chorea (CASE 8-2). Additional antibodies targeting intracellular antigens
● Antiphospholipid
include anti-Ma and antibodies directed at P/Q calcium channels. These antibodies are associated
antibodies indicate a T-cell–mediated immune response and may be less with systemic lupus
responsive to immunotherapy. Antibodies to cell surface proteins, including erythematosus,
leucine-rich glioma inactivated protein 1 (LGI1), contactin-associated hypercoagulability, and
chorea.
proteinlike 2 (CASPR2), and NMDA antibodies, may be more likely to
improve with immunotherapy. As noted above, anti-NMDA antibodies have ● IgLON5 is an antibody that
been associated with ovarian teratomas but may also be seen as described has been discovered
above without a neoplasm.40,67 recently in association with
parasomnias but can be
associated with cognitive
STRUCTURAL/LESIONAL CHOREA. Any structural lesion involving the basal impairment, gaze palsies,
ganglia has the potential to cause chorea. In the perinatal period, vascular and chorea.
phenomena leading to cerebral palsy can frequently cause choreiform and
dystonic movements. Dyskinetic cerebral palsy represents 14% of all cases of ● Structural or vascular
lesions should be
cerebral palsy. Although imaging may show periventricular leukomalacia or considered in cases of focal
thalamic and basal ganglia lesions, normal structural imaging is also common or hemibody chorea.
in these cases.66 Focal lesions occurring at any age, including ischemic strokes,
hemorrhages, demyelinating lesions, and space-occupying lesions (ie,
neoplasms), can cause chorea in the contralateral limbs when involving basal
ganglia structures. Of hemorrhagic or ischemic strokes, 1% to 4% have been
associated with movement disorders contralateral to the side of the injury,
with movements including chorea, hemiballismus, and dystonia. The onset
can be acute at the time of the stroke or delayed. Lesions in the caudate,
putamen, globus pallidus, subthalamic nucleus, or thalamus can all be
associated with chorea.68 Polycythemia vera, a myeloproliferative disorder,
has also been associated with chorea. It has been suggested to occur as a result
of hyperviscosity impacting blood flow to the basal ganglia, although an
underlying molecular explanation has also been proposed. Imaging the brain
to look for a structural lesion is the first step in diagnosis whenever a patient
presents with hemibody or focal-onset chorea.
PARAINFECTIOUS CHOREA. Chorea can be caused by viral infections, either

as a result of a cytotoxic effect of the virus or by a cytokine-mediated or
parainfectious mechanism. When chorea occurs in the setting of a viral
infection, it typically has an acute or subacute onset and develops over the
course of the infection itself. It is often associated with encephalopathy and

CHOREA
other signs of systemic illness. It can be unilateral or generalized and typically

improves over days to weeks as the infection is treated. Viruses associated
with chorea include measles, mumps, rubella, varicella-zoster, influenza,
herpesvirus, Epstein-Barr virus, tick-borne encephalitis, West Nile
encephalitis, cytomegalovirus, Japanese B encephalitis, and HIV.40 In HIV,
chorea can be the direct result of the virus or due to other opportunistic
infections (eg, toxoplasmosis, syphilis). Most TORCH infections (as described
in the section on basal ganglia calcifications) can also cause chorea.
TOXIC/METABOLIC CAUSES OF CHOREA. Medication-induced chorea is common

and frequently encountered in neurologic practice. Levodopa-induced
CASE 8-2 A 78-year-old man was referred to the movement disorder clinic by his
primary neurologist for further evaluation of new-onset involuntary
movements. The patient reported involuntary movements in his upper
and lower extremities, impaired gait, and worsening balance for the past
few months. He did not have any psychiatric symptoms. He reported a
recent unintentional weight loss of approximately 9 kg (20 lb) over a
2-month period. He denied any significant past medical history. He had
no history of alcohol or illicit drug use; however, he did endorse previous
tobacco use (an approximately 30-pack-year history). The patient denied
any family history of chorea or any neurologic diseases.
Neurologic examination revealed normal ocular pursuit, slightly
delayed saccade initiation and velocity, and involuntary nonrhythmic
moderate-amplitude purposeless movements throughout but more
prominent in the lower extremities (VIDEO 8-5). Gait revealed a slightly
widened base, shortened stride, inability to attempt tandem, and
positive pull test. The remainder of the neurologic examination was
normal, including strength, sensation, tone, and reflexes.
The initial laboratory workup was normal. CSF studies revealed
elevated protein and elevated white blood cell count with lymphocytic
predominance and normal glucose. No malignant cells were detected on
flow cytometry. Brain MRI demonstrated subtle T2 hyperintensities in the
striatum. Chest CT revealed a circumscribed lesion in the right lower lobe
and hilar lymphadenopathy. A paraneoplastic panel was positive for
collapsin response mediator protein-5 (CRMP-5) IgG antibodies in the
serum and CSF. Biopsy of the right lower lobe lesion revealed small cell
carcinoma of the lung. The patient received a brief course of IV
methylprednisolone. Tumor resection and chemotherapy led to
resolution of the chorea.
COMMENT In this patient, the duration of symptoms (subacute), unintentional weight

loss, and history of smoking suggested a paraneoplastic etiology. Although
chorea of paraneoplastic etiology is rare, a high level of vigilance should be
maintained in the appropriate clinical context. Chorea generally resolves
after the identification and removal of the underlying malignancy.
1392 OCTOBER 2022

dyskinesia in patients with PD and tardive dyskinesia from chronic KEY POINTS
neuroleptic exposure are among the most common causes of chorea.69
● Dopaminergic
Levodopa-induced dyskinesia occurs in approximately 50% of people with PD medications and
at 5 years and correlates with disease duration, higher doses of levodopa, lower antidopaminergic
weight, female sex, and younger age at onset. Multiple pathogenic medications can cause
mechanisms have been described, including pulsatile, nonphysiologic choreiform movements.
Careful medication history
stimulation of dopamine receptors.70 Prolonged exposure to
and timeline of exposure are
dopamine-receptor blocking agents, such as many antipsychotic and important.
antiemetic medications, leads to dopamine receptor hypersensitivity. The
result is often a characteristic buccolingual masticatory chorea, although any ● Hyperglycemia is a
region of the body can be involved. Other pharmacologic agents that have common metabolic cause of
acute-onset chorea
been reported to cause chorea include central nervous system stimulants (eg, associated with T1 signal
amphetamines), anticholinergics, antihistamines, antidepressants, antiseizure change in the contralateral
medications, and oral contraceptives (TABLE 8-2).16,19,23,71 In most cases, the chorea putamen on MRI.
remits with removal of the offending agent, but with tardive dyskinesia,
movements may sometimes persist or worsen even once the offending agent
is discontinued.
Various metabolic derangements have been associated with chorea, the most
common of which is acute-onset chorea secondary to nonketotic hyperglycemia
(CASE 8-3 and VIDEO 8-6), in which a characteristic hyperintense T1 signal is
often seen in the contralateral putamen. Additional endocrinologic changes
associated with chorea include hypocalcemia, hypoparathyroidism,
hyponatremia or hypernatremia, hypomagnesemia, and uremia. Toxins,
including carbon monoxide, manganese, organophosphates, and mercury, have
also been associated with basal ganglia injury and subsequent chorea.16,24,40
APPLYING FOUR FEATURES IN THE DIAGNOSIS OF CHOREA

Various algorithms can guide the assessment of a patient with chorea.16,24,39,40
Considering the time course, age of onset, comorbid history/examination
findings, and comorbid data findings may aid the clinician in distinguishing
between causes of chorea and developing a more targeted diagnostic plan
(TABLE 8-3 and TABLE 8-4). Hereditary causes are more often insidious and
chronic, whereas acquired causes may have a more subacute presentation. Static
and paroxysmal causes have also been discussed. Episodic chorea can be seen in
paroxysmal kinesigenic and nonkinesigenic dyskinesia, while static chorea is
more likely due to an acquired cause such as a vascular lesion. Childhood onset
often raises suspicion for Sydenham chorea, whereas adult onset should raise
suspicion for HD and HD mimics. Further inquiry into ethnicity; inheritance
pattern; drug exposures; location of the chorea (eg, focal, diffuse,
orobuccolingual); and comorbid neurologic, psychiatric, systemic, and cognitive
features may guide diagnosis. Finally, bloodwork and imaging may aid in the
diagnosis of select hereditary, structural, autoimmune, or metabolic causes.
In adults, genetic counseling followed by an HD gene test remains the most
appropriate first step when hereditary chorea is suspected given the prevalence
of HD compared to other hereditary conditions. If the HD test is negative,
additional workup can be guided by the clinical phenotype, presumed
inheritance pattern, and additional test results. Among HD phenocopies, Wild
and colleagues16 reported that SCA17 accounts for 1.1% of HD phenocopies,
HDL2 for 0.7%, Friedreich ataxia (JPH3) for 0.35%, and inherited prion disease
( PRNP) for 0.24%. Testing for these pathogenic variants can now be performed

CHOREA
via a single panel, or targeted assessments can be done based on features

described of each above. In a 2014 review of 514 HD phenocopies, 1.95% were
found to have the C9orf72 expansion, leading the authors to propose this
pathogenic variant as the most common phenocopy to test for after an HD gene
test is negative.52 Regardless, the majority of patients with HD phenocopies still
do not attain a formal genetic diagnosis.
MANAGEMENT OF CHOREA
Chorea may cause physical disability, functional impairment, and social isolation.
It is important to understand the impact of the chorea on the patient’s well-being
and function to determine whether treatment is warranted. In some conditions
such as HD, it is often outsiders or family members who notice the chorea more
than the patient. The first step in managing chorea is to determine whether the
impact of the movements requires treatment at all. Chorea that is mild and does
TABLE 8-2 Drugs That May Induce Choreaa
Antidepressants
◆ Fluoxetine
◆ Fluvoxamine
◆ Paroxetine
◆ Tricyclic antidepressants
Antiseizure medications
◆ Carbamazepine
◆ Ethosuximide
◆ Lamotrigine
◆ Phenytoin
◆ Phenobarbital
◆ Valproic acid
◆ Zonisamide
Antihistamines (H1 or H2 blockers)
◆ Cimetidine
◆ Cyclizine
◆ Cyproheptadine
◆ Diphenhydramine
Antiparkinsonian drugs
◆ Levodopa
◆ Dopamine agonists
◆ Anticholinergic drugs (eg, trihexyphenidyl)
CONTINUED ON PAGE 1395
1394 OCTOBER 2022

not interfere with daily function, dexterity, or mobility does not necessarily need
to be treated. It is important to be aware, however, that lack of awareness of
deficits (anosognosia) is a common feature of some neurodegenerative diseases,
including HD. As a result, the clinician and family should attempt to judge the
impact of the chorea in collaboration with the patient.
Management of Secondary Chorea

When chorea results from an underlying disease, disease-specific therapy is often
the most effective approach to treatment.41 It is important not to miss the
opportunity to treat conditions that are reversible. Chorea that results from
structural, metabolic, or infectious causes can often be self-limited and may not
require symptomatic treatment outside of the acute setting. Therapies for
specific causes of chorea include penicillin for Sydenham chorea; antimicrobials
for central nervous system infections; immunotherapy for autoimmune
CONTINUED FROM PAGE 1394
Calcium-channel blockers
◆ Flunarizineb
◆ Verapamil
Dopamine antagonists
◆ Butyrophenones
◆ Benzamides
◆ Dopamine antagonist antiemetics
◆ Phenothiazines
Psychostimulants
◆ Amphetamines
◆ Cocaine
Other medications
◆ Baclofen
◆ Cyclosporine
◆ Digoxin
◆ Fluoroquinolones
◆ Lithium
◆ Methadone
◆ Methotrexate
◆ Oral contraceptives, estrogen replacement therapy
◆ Steroids
◆ Theophylline
a
Data from Mestre TA,19 Cardoso F, et al,24 and Zesiewicz TA and Sullivan KL.71
b
Flunarizine is not currently approved by the US Food and Drug Administration (FDA) to be marketed in the
United States.

CHOREA
conditions; blood sugar control for hyperglycemia; management of abnormalities

in sodium, calcium, or thyroid levels; chelation for Wilson disease; and
phlebotomy for polycythemia. For chorea due to paraneoplastic causes,
immunotherapies may be used, but treating the underlying cancer is critical.
Chorea that is caused by levodopa often improves with reducing the dose of
levodopa and/or supplementing with other medications such as amantadine. Of
note, an extended-release form of amantadine has been approved to manage
levodopa-induced chorea.74 For tardive dyskinesia, vesicular monoamine
transporter-2 (VMAT2) inhibitors (often called dopamine depleters) are
recommended, and evidence is insufficient to support or refute withdrawing or
switching the offending/causative agent. Instead, the appropriateness of the
offending agent should be reviewed and assessed, and if necessary,
dopamine-depleting agents are recommended.75
Most genetic causes of chorea are treated symptomatically; however, Wilson
disease is an exception. Screening for Wilson disease early whenever suspicion
CASE 8-3 A 91-year-old right-handed man presented to the emergency department

with insidious-onset right arm pain. During the emergency department
evaluation, he was noted to have abnormal movements described as
involuntary dancing movements involving the right arm and leg. The
patient was unaware of these symptoms and could not state the onset
time but suggested that perhaps it was present for a few weeks or
months at most. No urge was associated with the movements. The patient
lived alone and reported being independent with activities of daily living.
He denied that the movements interfered with any activities of daily
living. His past medical history was notable for hypertension and newly
diagnosed type 2 diabetes mellitus. No medication changes had been
made recently, and he was not taking any medication for diabetes. He
denied any significant neurologic family history.
On examination, the patient had involuntary nonrhythmic, asynchronized,
midfrequency, mid- to high-amplitude writhing/dancelike movements in
the right upper and lower extremities. The movements were more proximal
than distal and not distractible. The intensity/amplitude reduced with
concentration. Intermittent irregular mouth movements were noted, which
disappeared when the patient was asked to relax. Initially, some overflow
movements on the left side were noted; however, they disappeared when
the patient relaxed. The arm movements were present at rest and with
action. The intensity of movement was moderate.
Brain MRI showed signal change in the left putamen on T1-weighted
images (FIGURE 8-272). His serum glucose was 380 mg/dL, and his hemoglobin
A1c was greater than assay (>13.9%). Eight months previously, his hemoglobin
A1c had been 7.2%.
A diagnosis of hyperglycemia-associated chorea was made. He was
hospitalized for a week, and glycemic control was achieved with insulin and
oral hypoglycemic medication. By the time of discharge, his choreiform
movements were significantly reduced and symptomatic therapy was not
initiated.73
1396 OCTOBER 2022

exists is critical because disease-modifying therapy with chelation and zinc can
reduce copper deposition, modify the disease course, and improve symptoms.62
For NBIA disorders, no clear treatment guidelines have been established,
although case reports of chelation therapies have been described in some of these
conditions.41 Paroxysmal kinesigenic dyskinesia and paroxysmal nonkinesigenic
dyskinesia may respond to antiseizure medications and dietary changes, as
discussed above. For other genetic causes of chorea, including HD, management
is primarily symptomatic and supportive.
Pharmacologic Management of Chorea

VMAT2 inhibitors deplete the release of dopamine presynaptically by preventing
packaging of monoamines into presynaptic storage vesicles. This results in fewer
movements as less dopamine is released from presynaptic terminals in the
nigrostriatal pathway. Two VMAT2 inhibitors are approved by the US Food and
Drug Administration (FDA) for the management of chorea related to HD:
FIGURE 8-2
Imaging of the patient in CASE 8-3. Axial
T1-weighted MRI shows signal change in
the left putamen.
Reprinted from Prakash N, Interactin.72
© 2022 John Wiley & Sons, Inc.
The acute to subacute onset of chorea in this patient, in addition to its COMMENT
location, pointed toward an acquired cause of chorea. The location
(hemichorea) suggests a structural or vascular etiology requiring
neuroimaging and laboratory studies, and in this case led to the diagnosis
of nonketotic hyperglycemia-associated chorea. Late-onset chorea can be
seen in Huntington disease; however, the location, timeline, family history,
and subsequent neuroimaging and laboratory findings eliminate this from
the differential.

CHOREA
TABLE 8-3 Differential Diagnosis of Hereditary Chorea
Pathogenic Select history Select laboratory

variant/ and examination and imaging
Disorder inheritance Onset Time course features findings
Huntington disease Autosomal Third to fourth Progressive Most common CAG repeat
dominant decades over hereditary chorea expansion (>35) in
15-20 years HTT
HTT on Juvenile Chorea and dystonia
chromosome Huntington are common Caudate/striatal
4p16.3 disease before atrophy on MRI
Parkinsonism and
age 20 (>55
seizures (juvenile)
repeats)
Other features:
36-39 repeats is
neuropsychiatric
reduced
disorder and dementia,
penetrance
motor impersistence,
range
impaired saccades
Paternal
anticipation
Huntington Autosomal Second to fifth Rapidly Huntington disease Octapeptide

disease–like 1 dominant decades progressive phenocopy repeat in PRNP
PRNP on Myoclonus, rapid MRI similar to
chromosome progression Huntington
20p13 disease
Huntington Autosomal Second to fifth Similar to Huntington disease CAG repeat

disease–like 2 dominant decades Huntington phenocopy expansion in JPH3
disease
JPH3 on African ancestry MRI similar to
chromosome Huntington
16q24.2 disease
Acanthocytes
may be present
Dentatorubral- Autosomal Adult- or Variable, Huntington disease CAG repeat

pallidoluysian dominant childhood-onset progressive phenocopy expansion in ATN1
atrophy forms
ATN1 on Japanese ancestry MRI fluid-
chromosome attenuated
May have seizures and
12p13 inversion recovery
myoclonus
(FLAIR) signal
Haw River syndrome in change in
North Carolina dentate, red
nucleus, pallidum
C9orf72 Autosomal Third to fifth Variable, Variable phenotypes GGGGCC repeat

dominant decades progressive seen, including expansion in
frontotemporal C9orf72
Chromosome 9
dementia and motor
hexanucleotide Generalized
neuron disease
expansion cerebral atrophy
(amyotrophic lateral
sclerosis)
Possibly the most
common phenocopy of
Huntington disease
1398 OCTOBER 2022


Spinocerebellar Autosomal First through Variable, Huntington disease CAG repeat

ataxia type 17/ dominant fourth decades, progressive phenocopy expansion in
Huntington variable TBP; cerebellar
TBP on White or Asian
disease–like 4 atrophy
chromosome populations
6q27
Ataxia
Friedreich ataxia Autosomal Typically Variable, Ataxia, areflexia, GAA repeat

recessive childhood onset progressive neuropathy, expansion in FTX
without chorea, cardiomyopathy,
FXN mutation Abnormal nerve
but adult/late diabetes, foot
on chromosome conduction
onset with deformities
9q21.11 studies
chorea is
possible
Chorea- Autosomal Second to fourth Variable, Orobuccolingual Acanthocytes on

acanthocytosis recessive decades, variable progressive chorea peripheral blood
smear
Chorein protein Self-injurious oral
VPS13A gene mutilation, Elevated creatine
hypersalivation, kinase
dysphagia, lingual
dystonia, rubber
man gait
McLeod syndrome X-linked Second to fifth Variable, Cardiomyopathy, Acanthocytes on

decades, variable progressive seizures, axonopathy peripheral blood
XK for Kx
smear
antigen on red
blood cell Elevated creatine
surface kinase
Neuroferritinopathy Autosomal Fourth to fifth Variable, Orobuccal chorea MRI with basal
dominant decades, variable progressive ganglia iron
Northern England
accumulation on
FTL on
T2-weighted and
chromosome
gradient recalled
19q13.33
echo (GRE) images
Low serum ferritin
Aceruloplasminemia Autosomal Fourth to fifth Variable, Dystonia, ataxia, MRI with basal
recessive decades, variable progressive diabetes, retinal ganglia iron
degeneration accumulation on
CP on
T2-weighted and
chromosome 3q
GRE images
Absent serum
ceruloplasmin

CHOREA
CONTINUED FROM PAGE 1399FROM PAGE 1399

CONTINUED

Fahr disease Autosomal Third to fourth Variable Tremor, parkinsonism CT/MRI with basal
dominant decades, variable ganglia,
brainstem,
SLC20A2 on
cerebellar
chromosome
calcifications
8p11.21
Other genes
include XPR1
Wilson disease Autosomal Childhood or Varies by Gastrointestinal Low serum

recessive early adult onset response to symptoms, ceruloplasmin,
(usually before treatment Kayser-Fleischer rings, elevated 24-hour
ATP7b on
age 50) wing-beat tremor, urine copper,
chromosome Can remain
dystonia, parkinsonism, elevated liver
13q14.3 stable with
ataxia enzymes,
chelation or be
elevated liver
cured with liver
copper, liver
transplantation
fibrosis/cirrhosis
Face of the giant
panda sign on
T2-weighted MRI
Benign hereditary Autosomal Childhood onset Static or slight Stable course None
chorea dominant progression
Pulmonary or thyroid
NKX2-1 (thyroid problems (brain-lung-
transcription thyroid syndrome)
factor) on
No dementia
chromosome
14q13.3
Adenylyl cyclase Autosomal Childhood onset Variable, Childhood hypotonia None

type 5 dominant paroxysmal
Facial myoclonus,
ADCY5 on worsening with sleep
chromosome deprivation
3q21.1
Paroxysmal Autosomal Childhood onset Paroxysmal Episodes lasting None

kinesogenic dominant seconds to minutes
dyskinesia
PRRT2 on Numerous per day,
chromosome triggered by movement
16p11.2 (DYT10)
Responsive to
carbamazepine
Paroxysmal Autosomal Childhood onset Paroxysmal Episodes triggered by None

nonkinesigenic dominant stress, extremes of
dyskinesia temperature, alcohol,
MR-1 gene on
or excitement
chromosome
2q35 (DYT8) Lasts minutes to hours
CT = computed tomography; EMG = electromyography; MRI = magnetic resonance imaging.
1400 OCTOBER 2022

tetrabenazine and deutetrabenazine. The TETRA-HD (Efficacy and Safety of KEY POINTS
Tetrabenazine in Chorea) study provided Class I evidence of the efficacy of
● It is important to
tetrabenazine based on improvement in motor chorea scores on the UHDRS.76 determine whether chorea is
Potential side effects that may limit the use of tetrabenazine include depression troublesome or bothersome
and suicidal ideation, sedation, and parkinsonism. Deutetrabenazine is also FDA before initiating a
approved for the management of HD chorea. It is chemically identical to medication. Anosognosia is
not uncommon, especially in
tetrabenazine, except that the metabolic profile is altered by replacing key
Huntington disease;
hydrogen atoms with deuterium. The incorporation of deuterium results in a therefore, collecting input
longer half-life, less frequent dosing, and more stable serum drug levels. The from the patient and their
FIRST-HD (First Time Use of SD-809 in Huntington Disease) study care partner is essential.
demonstrated significant improvement in UHDRS scores in patients with HD
● Vesicular monoamine
compared to placebo.77 Deutetrabenazine was also studied for the management transporter-2 (VMAT2)
of tardive dyskinesia, and the ARM-TD (Aim to Reduce Movements in Tardive inhibitors are the only class
Dyskinesia) study demonstrated Class I evidence of improvement in AIMS of medications currently
scores in this population compared to placebo.78 Deutetrabenazine is now approved by the US Food
and Drug Administration for
approved for the management of HD chorea and tardive dyskinesia, and has the treatment of tardive
been used off label for the management of other forms of chorea. It is thought to dyskinesia and/or chorea
have less potential for side effects, such as mood disorders and sedation, than associated with Huntington
tetrabenazine, but patients should still be monitored for changes in mood, disease.
suicidal ideation, and parkinsonism. Another VMAT2 inhibitor, valbenazine, is
also FDA approved for the management of tardive dyskinesia. Valbenazine has a
once-daily dosing profile and was shown in the KINECT-3 (A Phase 3 Study of
NBI-98854 for the Treatment of Tardive Dyskinesia) trial to effectively improve
AIMS scores compared to placebo in patients with tardive dyskinesia.79 It is
currently being studied for other conditions, including HD chorea.
Neuroleptics are frequently used off-label for the management of chorea in
various disorders, including HD. D2-receptor blockade occurs with both typical
and atypical neuroleptics and results in inhibition of the indirect pathway,
thereby reducing movements. Despite having less disease-specific evidence for
their use in chorea, neuroleptics are often used as adjunctive treatments for
behavioral and psychiatric issues in HD and other degenerative choreas. They are
sometimes also considered off-label for effects on weight gain and sleep.
Neuroleptics with greater D2 blockade, such as typical neuroleptics, risperidone,
and olanzapine, may be more effective in treating chorea than neuroleptics such
as quetiapine and clozapine, which have lower D2 blockade. Neuroleptics should
be used with caution because of the risk of metabolic syndrome, somnolence,
parkinsonism, and tardive dyskinesia.
Another medication that is sometimes used off-label in the management of
chorea is the NMDA receptor antagonist amantadine. Evidence for the benefit of
amantadine has already been discussed in the context of levodopa-induced
dyskinesia, but evidence for use in other forms of chorea, including HD and
tardive dyskinesia, is limited.
Antiseizure medications have multiple sites of action, including in the basal
ganglia, although they are rarely used in the neurodegenerative choreas. These
medications are used more often in pediatric patients and can be useful in
patients who also have seizures, such as those with neuroacanthocytosis, juvenile
HD, or DRPLA.80
When chorea is comorbid with dystonia, particularly when the onset is focal,
botulinum toxin injections may be considered. However, botulinum toxin is not
approved specifically for the management of chorea.

CHOREA
TABLE 8-4 Differential Diagnosis of Acquired Chorea
Select history and Select laboratory and

Category/disorder Onset Time course examination features imaging findings
Sydenham chorea Childhood or early Self-limited Ticlike behaviors, Throat culture (group A
adolescence irritability, inattention streptococci), anti-
streptolysin-O antibody,
Acute onset History of
anti-DNAse antibody
streptococcal
After strep
infection
infection
Can be associated
with chorea
gravidarum later in life
Other autoimmune
disorders
Systemic lupus Often middle-age NMDA is rapidly Systemic features for Erythrocyte sedimentation
erythematosus/ adulthood; insidious progressive; relevant condition (ie, rate, antinuclear antibody
antiphospholipid in the context of a others are variable rash, arthralgia, panel, celiac antibodies,
antibody syndrome systemic disease oral ulcers); anti–double-stranded DNA
or subacute primary thrombotic events/ antibody, anticardiolipin,
Behçet disease,
manifestation miscarriages lupus anticoagulant
Sjögren syndrome,
for antiphospholipid antibodies, pregnancy test
celiac disease
antibody syndrome (chorea gravidarum),
anti-NMDA antibody,
anti-IgLON5 antibodies
in serum or CSF
Anti-N-methyl-D- NMDA is subacute NMDA is associated

aspartate (NMDA) with limbic encephalitis
receptor encephalitis and ovarian teratomas
IgLON5 IgLON5 is usually IgLON5 is associated

insidious in middle with parasomnias,
age cognitive impairment,
and gaze palsies
Paraneoplastic
Small cell lung cancer, Adulthood Progressive, may Systemic findings, Anti-Hu, collapsin
ovarian teratomas Subacute be associated with although the response mediator protein
encephalitis and neurologic features (CRMP-5), anti-Ma, and
development of may appear before antibodies directed at the
systemic systemic findings are P/Q calcium channel,
symptoms in some present leucine-rich glioma
cases inactivated 1 (LGI1),
contactin-associated
proteinlike 2 (CASPR2),
NMDA
CT or positron emission
tomography (PET) scan of
full body, testicular
ultrasound/testicular
ultrasound
1402 OCTOBER 2022

Select history and Select laboratory and

Category/disorder Onset Time course examination features imaging findings
Structural/lesional
Cerebral palsy/ Perinatal period Cerebral palsy has Hemibody or focal MRI of the brain
periventricular for cerebral palsy/ stable, chronic chorea with stroke, hemorrhage,
leukomalacia periventricular course or other focal basal
May be associated
leukomalacia ganglia pathology
Ischemic stroke, Strokes and with signs of elevated
hemorrhage Any age for other demyelinating intracranial pressure if
causes listed lesions may be space-occupying
Demyelinating lesion
most severe at lesion
Acute/subacute
Other space-occupying onset and may
lesion: neoplasm, abscess gradually improve
Space-occupying
lesions may be
slowly progressive
Parainfectious
Measles, mumps, rubella, Acute or subacute Often follows the Often associated Brain imaging, viral panels
varicella-zoster virus, course of the with systemic illness in serum and CSF
influenza, herpesvirus, infection or encephalopathy;
Epstein-Barr virus, unilateral or
tick-borne encephalitis, generalized; viral
West Nile encephalitis, causes tend to
cytomegalovirus, improve with
Japanese encephalitis, resolution of
human immunodeficiency the infection
virus (HIV)
Toxic/metabolic
Medications (refer to Improvement with
TABLE 8-2) correction or removal
of offending agent
Hyperglycemia, Variable; typically Static or Complete blood cell count,

hypocalcemia, insidious with progressive with chemistry (including
hypoparathyroidism, medications, but medications, then glucose, sodium, calcium,
hyponatremia, more acute with static or improved thyroid function tests,
hypernatremia, metabolic or toxic with removal of and parathyroid tests)
hypomagnesemia, causes; any age offending agent
uremia Brain MRI
Polycythemia Static with toxic Hematocrit raised in

injury to basal polycythemia
ganglia
Carbon monoxide, Gradual History of exposures

manganese, mercury, improvement with
organophosphates resolution of
metabolic
derangement
CSF = cerebrospinal fluid; CT = computed tomography; DNA = deoxyribonucleic acid; MRI = magnetic resonance imaging.

CHOREA
Research on the use of cannabinoids for chorea is inconclusive. Cannabinoid

receptors are present throughout the basal ganglia; cannabinoid receptor
type 1 (CB1) receptors, in particular, are reduced as part of the degenerative
process in HD. Although this suggests a rationale for manipulation of the
endocannabinoid system in the symptomatic management of hyperkinetic
movements, randomized controlled studies have thus far shown
inconsistent results.80,81
Nonpharmacologic Management of Chorea

Deep brain stimulation may be a treatment option for medication-refractory
hyperkinetic movement disorders. Deep brain stimulation has been studied in
HD chorea and tardive dyskinesia, but usage remains investigational
(VIDEO 8-7). Targeting the globus pallidus internus has been shown to have
antichoreic effects, but the cognitive and neuropsychiatric features of
degenerative conditions such as HD make this a limited treatment option in
most cases.82
A multidisciplinary approach to the management of chorea is critical to
address the movements themselves as well as the comorbid complications
associated with many conditions that cause chorea, such as HD. Addressing
the psychiatric and cognitive aspects of neurodegenerative diseases is as
important as managing the motor aspects. Individuals with neurodegenerative
diseases can benefit from working with speech, occupational, and physical
therapists; social workers; psychiatrists; neuropsychologists; and genetic
counselors to address the myriad of functional and social issues associated
with their disease. Caloric demands are higher among individuals
with chorea, particularly in HD, and nutrition consultations may be
helpful in developing a healthy high-caloric diet. Trunk and limb chorea may
lead to balance disorders and falls; therefore, working with physical
therapists on balance training and core strengthening and implementing
assistive devices may be useful. Multidisciplinary rehabilitation programs
have been shown to improve motor and balance deterioration in people
with HD.83
CONCLUSION
Neurologists should recognize the pattern of involuntary, random,
nonrhythmic, purposeless, movements as consistent with chorea. Collecting a
detailed history and identifying the location of the chorea in addition to
supportive neurologic signs will help narrow the differential and focus the
diagnostic and therapeutic approach. If the chorea negatively impacts quality
of life and functional independence, symptomatic medications are available. A
multidisciplinary approach is preferred when treating individuals with
chorea, especially those with a multifaceted neurodegenerative disease such
as HD.
ACKNOWLEDGMENT
The authors would like to thank Shayan A. Zadegan, MD, for assistance with the
literature review.
1404 OCTOBER 2022

VIDEO LEGENDS
VIDEO 8-1 VIDEO 8-5
Huntington disease. Video shows a 33-year-old Generalized chorea secondary to CRMP5
man with genetically confirmed early-onset antibodies. Video shows the 78-year-old man in
Huntington disease. Examination reveals slowed CASE 8-2 who presented with a subacute onset of
ocular pursuit, saccade initiation and velocity, motor generalized chorea. The nonrhythmic
impersistence (impaired sustained tongue moderate-amplitude purposeless appendicular
protrusion), impaired finger tapping and pronation/ movements are generalized, slightly more
supination and Luria hand sequences, generalized prominent in the lower extremities. Gait reveals a
bradykinesia, and chorea. Gait is wide based with slightly widened base, shortened stride, and distal
bilateral upper extremity dystonic posturing. upper extremity chorea.
© 2022 American Academy of Neurology. Video courtesy of Bill Ondo, MD.
VIDEO 8-2 VIDEO 8-6

Huntington disease. Video shows a 42-year-old Hemichorea secondary to nonketotic
man with motor manifest Huntington disease hyperglycemia. Video shows a 51-year-old woman
demonstrating generalized chorea, impaired rapid with left hemichorea, which involves her face, arm,
finger tapping, and pronation/supination. and leg. Her serum glucose level was 527 mg/dL
Appendicular chorea and dystonia are seen during with a hemoglobin A1C of 12.6%. The brain MRI of the
attempted tandem gait. patient demonstrated T1 hyperintensity in the right
© 2022 American Academy of Neurology. posterior putamen. The history, imaging, and clinical
presentation led to a diagnosis of hemichorea
secondary to nonketotic hyperglycemia.
VIDEO 8-3
Generalized chorea secondary to benign Video courtesy of Amy Durand, MD, and Jorge
hereditary chorea. Video shows the 34-year-old Patino Murillas, MD.
woman in CASE 8-1 with chronic generalized
nonrhythmic moderate-amplitude purposeless VIDEO 8-7
truncal and appendicular movements. The patient Hemiballismus secondary to deep brain
has a strong family history of chorea (father and two stimulation of the subthalamic nucleus. Video
young daughters) and has a history of asthma and shows a 64-year-old woman with Parkinson disease
hypothyroidism suggestive of a clinical diagnosis of who presented with an acute onset of left
benign hereditary chorea due to mutation in the hemiballismus that occurred after programming
NKX2-1 gene. deep brain stimulation (DBS) of the right
subthalamic nucleus. The patient experienced
© 2022 American Academy of Neurology.
involuntary, high-amplitude proximal movements in
the left upper and left lower extremity. The
VIDEO 8-4 movements resolved with deep brain stimulation
Sydenham chorea. Video shows a 10-year-old boy reprogramming.
who presented with a subacute onset of
generalized chorea that began after an infection Video courtesy of Gage Van Horn, MD.
with group A streptococcus.
Video courtesy of Bill Ondo, MD.
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1471-2377-9-62
DISCLOSURE
Continued from page 1379 Kyowa Kirin Co, Ltd; Neurocrine Biosciences, Inc;
and Teva Pharmaceutical Industries Ltd and as an
Huntington's Disease Society of America; F. editor, associate editor, or editorial advisory board
Hoffman-La Roche/Genetech, Inc; the National member for the Annals of Clinical and Translational
Institutes of Health/University of Iowa; uniQure NV; Neurology/American Neurological Association.
and Vaccinex Inc. Dr Bega has received personal The institution of Dr Bega has received research
compensation in the range of $500 to $4999 for support from the Huntington’s Disease Society of
serving on speakers bureaus for Acorda America.
Therapeutics; Adamas Pharmaceuticals, Inc;
1408 OCTOBER 2022

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Chorea REVIEW ARTICLE

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chorea may vary from subtle low-amplitude movements of varying frequency

CHOREA VERSUS OTHER HYPERKINETIC MOVEMENTS

1380 OCTOBER 2022

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HEMICHOREA. Hemichorea has been classically associated with focal vascular

Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

(HIV) and acquired immunodeficiency syndrome (AIDS).16,22,23 Some

OROBUCCOLINGUAL CHOREA. Orobuccolingual chorea may present in several

FACIAL OR FOREHEAD CHOREA. Chorea involving the forehead/upper face,

1382 OCTOBER 2022

Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

APPROACH TO THE DIAGNOSIS OF CHOREA

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HUNTINGTON DISEASE. HD is the most common cause of adult-onset hereditary

TABLE 8-1 CAG Repeats in Huntington Diseasea

<26 Normal Will not be affected None

36-39 Reduced penetrance May or may not be affected 50%

40+ Full penetrance Will be affected 50%

1384 OCTOBER 2022

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HUNTINGTON DISEASE MIMICS/PHENOCOPIES. Hereditary conditions that mimic

HUNTINGTON DISEASE–LIKE DISORDERS. Four genes associated with Huntington

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ataxia type 17 (SCA17) and is discussed in the section on spinocerebellar ataxia

DENTATORUBRAL PALLIDOLUYSIAN ATROPHY. Similar to HD, dentatorubral

C9ORF72. Expanded hexanucleotide repeat pathogenic variants in the C9orf72

SPINOCEREBELLAR ATAXIA TYPE 17 AND OTHER HEREDITARY ATAXIAS. Many primary

OTHER HEREDITARY CHOREAS. Inheritance patterns for hereditary causes of

NEUROACANTHOCYTOSIS. Neuroacanthocytosis refers to a group of extremely rare

1386 OCTOBER 2022

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HEREDITARY DISORDERS ASSOCIATED WITH BASAL GANGLIA MINERALIZATION. ● Pathogenic variants in

BASAL GANGLIA CALCIFICATIONS/FAHR DISEASE. Minor calcifications in the basal

WILSON DISEASE. Wilson disease is an autosomal recessive genetic disorder that

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CASE 8-1 A 34-year-old right-handed woman presented to the clinic for

1388 OCTOBER 2022

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BENIGN HEREDITARY CHOREA. Familial forms of chorea that have an onset in

ADCY5-RELATED CHOREA. Adenylyl cyclase 5 (ADCY5) mutation-related

PAROXYSMAL KINESIGENIC AND NONKINESIGENIC DYSKINESIA. Paroxysmal

Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

SYDENHAM CHOREA. Sydenham (or poststreptococcal) chorea is the most

SYSTEMIC LUPUS ERYTHEMATOSUS AND OTHER AUTOIMMUNE-RELATED CHOREAS.

1390 OCTOBER 2022

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PARAINFECTIOUS CHOREA. Chorea can be caused by viral infections, either

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other signs of systemic illness. It can be unilateral or generalized and typically

TOXIC/METABOLIC CAUSES OF CHOREA. Medication-induced chorea is common

COMMENT In this patient, the duration of symptoms (subacute), unintentional weight

1392 OCTOBER 2022

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APPLYING FOUR FEATURES IN THE DIAGNOSIS OF CHOREA

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via a single panel, or targeted assessments can be done based on features