Acute and Chronic Chorea in Childhood

Donald L. Gilbert, MD, MS

This review discusses diagnostic evaluation and management of chorea in childhood.

Chorea is an involuntary, hyperkinetic movement disorder characterized by continuous,
jerky, or flowing movement fragments, with irregular timing and direction. It tends to be
enhanced by voluntary actions and generally causes interference with fine motor function.
The diagnostic evaluation begins with accurate classification of the movement disorder
followed by consideration of the time course. Most previously healthy children presenting
with acute/subacute chorea have an autoimmune etiology. Chronic chorea usually occurs
as part of encephalopathies or diseases causing more global neurologic symptoms. We
review the management of acute/subacute and chronic choreas, with special emphasis on
Sydenham chorea and benign hereditary chorea.
Semin Pediatr Neurol 16:7176 2009 Published by Elsevier Inc.

C horea is a nonpatterned, involuntary, hyperkinetic

movement disorder. It is continuous, variable in speed,
unpredictable in timing and direction, and flowing or jerky in
genetic chorea, will be emphasized. Paroxysmal movement
disorders involving chorea will not be discussed but are re-
viewed elsewhere.4 As the phenomenology of chorea over-
appearance.1 Chorea may be accompanied by athetosis or laps in acute and chronic choreas, most features of the neu-
ballism. Athetosis is also continuous but the rate is slower. rologic examination will be discussed under acute chorea.
Athetosis often accompanies dystonia or occurs in symptom-
atic chorea and may be referred to as choreoathetosis. Ballism
designates larger amplitude, flinging, proximally generated Acute Chorea
movements. It rarely occurs in isolation in children but can
accompany chorea. Clinical Characteristics
Anatomically, chorea classically most often results from of Acute/Subacute Chorea
disturbances in the caudate or putamen.2 Occasionally, the History of Present Illness
source may be thalamic/subthalamic.3 A number of neurode- In childhood, chorea is most often acquired acutely or sub-
generative ataxias can also present with prominent chorea. acutely. It interferes with purposeful movements and often
Because of the vulnerability of the basal ganglia and its with speech. Parents can describe the hour, day, or week of
connections to a wide variety of pathologies, the differential onset and the way in which the childs speech and purposeful
diagnosis of acute and chronic chorea is very large. Genetic movements have changed. In subtle cases, parents will report
and metabolic diseases, endocrine disturbances, autoim- that coordination or speech has been affected in ways that
mune disorders, infections, cerebrovascular disease, neo- may not be apparent to the examiner. When the observable,
plasms, neurodegenerative diseases, toxins, and trauma can choreic movements are being discussed in clinic, children
all result in chorea. A detailed review of the entire spectrum with mature communication and awareness should be able to
of these diseases would exceed space limitations for this ar- describe the subjective nature of the movements, that is, the
ticle. This review will discuss acute and chronic chorea, em- movements are involuntary, nonsuppressible, and not per-
phasizing clinical diagnosis and management. Sydenham formed in response to an urge or sensation. They may de-
chorea, the most common acute/subacute acquired chorea in scribe that the movements make them clumsy and that their
childhood, and benign hereditary chorea, a rare but primary speech is slurred or slow. The movements generally cause
functional interference. This can be gauged by asking about
difficulties with activities of daily living.
From the Movement Disorders Clinics, Cincinnati Childrens Hospital Med- A careful history of possible antecedents to acute chorea is
ical Center, Cincinnati, OH. critical. As the most common etiology is autoimmune and
Address reprint requests to Donald L. Gilbert, MD, MS, Division of Neurol-
ogy, Cincinnati Childrens Hospital Medical Center ML 11006 and Neu-
poststreptococcal, a careful history of known or possible up-
rology, 3333 Burnet Avenue, Cincinnati OH. E-mail: donald.gilbert@ per respiratory infections or other illnesses should be sought.
cchmc.org Exposures to and doses of psychiatric and other medications,

1071-9091/09/$-see front matter 2009 Published by Elsevier Inc. 71

doi:10.1016/j.spen.2009.03.009
72 D.L. Gilbert

Table 1 Neurologic Examination in the Child With Chorea

Neurologic Examination Key Findings
Mental status Emotional changes may be present as part of or in response to the disease. Note that the
presence of involuntary facial movements that do not match the childs mood or meaning
may confound assessment.
Cranial nerve May be normal. Slurring of speech due to motor control problems of face and tongue, and
not due to brainstem or cranial nerve pathology.
Motor examination Bulk and reflexes may be normal; tone may be normal or low. Strength may appear weak due
to motor impersistence, ie, involuntary relaxations or choreic intrusions on sustained motor
output. Classic examples include milk maids grip during sustained grip and darting
tongue during sustained tongue protrusion.
Actions enhance chorea. With arms outstretched horizontally, hands pronated, and fingers
spread wide, there may be hyperextension at the metacarpophalangeal joints (a dystonic
posture referred to as spooning) and irregular distal movements. The touchdown sign
is an inability to maintain hands and arms fully extended and supinated over head due to
chorea. Additional tasks, such as talking or protruding tongue, may magnify hand/arm
findings.
Sensory examination Typically normal. Significant sensory hypersensitivity suggests akathisia rather than chorea.
Cerebellar and gait Important and sometimes challenging to discern. Cerebellar dysfunction on finger to nose
and gait/tandem gait testing should be fairly regular. In contrast, basal ganglia dysfunction
results in interference due to irregularly timed choreic intrusions on the trajectory of limb
movements, causing the finger to miss the target or the gait to lurch. In some diseases,
cerebellar and basal ganglia dysfunction co-occur.

exposure to toxins, detailed medical and developmental his- Diagnostic Approach

tory, recent psychological stressors, and review of systems The critical component is identifying and classifying the
should be routinely obtained. movement disorder. Once established that the problem is
General and Neurologic Examination acute chorea, the history should point to a relatively limited
During the process of taking the history, the clinician will number of categories of disease, and from there the testing
generally observe that the childs trunk appears restless and is can be targeted. Selected etiologies are listed in Table 2.
moving continuously in a random manner that is distinct
from titubation seen in ataxias. The child with acute chorea
may have generalized or localized dyskinetic movements.
Usually, there is prominent involvement of the face and 1 or Table 2 Etiology of Acute Chorea in Childhood: Categories
both arms and hands. Irregularly flowing or jerking, contin- and Selected Examples
uous movements give an appearance of restlessness. Facial Etiologic
and tongue chorea may slur or slow speech. Marked asym- Category Examples
metry of upper limb chorea may occur. Autoimmune Poststreptococcal, Sydenham chorea5
The general examination is important for other signs of Systemic lupus erythematosis6
illnesses, particularly those indicating autoimmune diseases Antiphospholipid antibody syndrome7
and infections. Skin, heart, joints, and lymph nodes should Other infections Herpes simplex virus,8 Mycoplasma9
be emphasized. Identifying an integral non-neurologic fea- and
ture of a disease narrows the differential diagnosis of the encephalitides
movement disorder. For example, the presence of joint in- Vascular/hypoxic Stroke; post cardiac transplantation
flammation or a systolic cardiac murmur supports an auto- ischemic post pump chorea in infants10
Static damage in dyskinetic cerebral
immune etiology.
palsy, markedly exacerbated
The neurologic examination should be thorough, empha- dyskinesia with febrile illness11
sizing portions of the examination related to basal ganglia Mitochondrial Mitochondrial encephalopathy with
and cerebellar function. The clinician should carefully observe disease lactic acidosis and stroke (MELAS):
the childs motor system at rest as well as while performing acute basal ganglia injury12
sustained movements and common actions. Videotaping the Toxins Carbon monoxide13
examination is helpful to allow reviewing phenomenology and Iatrogenic Dopamine receptor blocking agents/
assessing severity over time. Key findings of the neurologic ex- neuroleptics/antipsychotics: acute,
amination are described in Table 1. tardive, withdrawal-emergent14
Finally, it is important to note that fairly continuous, fre- Psychostimulants
quent myoclonus, particularly with dystonia, may lead to a Anticonvulsants
Psychogenic Conversion disorder15
movement disorder that appears identical to chorea.
Acute and chronic chorea in childhood 73

Diagnostic Testing infections, based on Jones criteria.17 GABHS are Gram-posi-

Laboratory Testing. A subacute course is most common tive bacteria that colonize or invade the upper respiratory
and supports an inflammatory disease, most commonly post- tract. In selected cases, possibly due to molecular mimicry,
streptococcal. Documenting a positive culture for group A an autoimmune response is triggered. The relationship of
-hemolytic streptococcal (GABHS) infection in the throat, GABHS to SC is supported by epidemiologic observations,
during the previous 6 months, helps confirm a diagnosis of including the reduction in cases in the post-antibiotic era and
Sydenham chorea (SC).16 Otherwise, blood testing for eleva- common co-occurrence of chorea and other manifestations
tions in streptococcal antibodies, anti-streptolysin O (ASO) of rheumatic disease, particularly carditis and arthritis.5
and anti-DNAse B (ADB), should be obtained, tested in an Chorea in SC develops over hours to days. Symptom se-
experienced laboratory, and compared against childhood verity varies widely but generally there is difficulty with fine
normative levels for that laboratory. It should be noted that motor tasks. Parents often report personality changes, in-
GABHS infections are highly prevalent and therefore elevated cluding inattention, anxiety, obsessive compulsiveness, para-
antibody titers are nonspecific. If ASO and ADB are not ele- noia, and reluctance to speak.18-22 Interestingly, children
vated, it is important to test for systemic lupus erythematosus with rheumatic fever not only commonly develop obsessive
and anti-phospholipid antibody syndrome. Referral to a compulsive symptoms, they also have a higher than expected
department of rheumatology may be considered. Chorea prevalence of these symptoms in first-degree relatives.23 Be-
caused by other infections, such as herpes simplex, Lyme cause SC is a form of rheumatic disease, it is critical to assess
disease, human immunodeficiency virus, mycoplasma pneu- the child carefully for the presence of a systolic heart murmur
monia, or Legionnaire disease may be considered in the ap- or of arthritis or arthralgia.5
propriate clinical setting, but this is extremely rare. The term SC should not be used interchangeably with the
term pediatric autoimmune neuropsychiatric disorders asso-
Neuroimaging. Obtaining a brain MRI scan to rule out brain
ciated with streptococcal infections (PANDAS). Key distin-
structural causes should be considered as part of the evalua-
guishing features are listed in Table 3.
tion of any child presenting with acute/subacute chorea.
Further discussion of PANDAS lies outside the scope of
However, in most cases where the clinical diagnosis is SC,
this review, but a number of recent studies are of interest.24-26
neuroimaging does not guide management.5 MRI findings
would also point toward diagnoses of mitochondrial/meta-
Management
bolic diseases, degenerative, neoplastic, and other inflamma-
Management involves education about the diagnosis and de-
tory diseases targeting the basal ganglia.
cisions about medical treatment. There is typically no role for
Neurophysiology. Electroencephalography, central motor occupational or physical therapy.
neurophysiological assessment with transcranial magnetic
Secondary Prevention of Group A -Hemolytic Streptococ-
stimulation, and electromyography are of interest in the
cal Infections. The standard of care for all children diag-
field of research. These studies do not routinely guide
nosed with SC, even in cases of isolated chorea with no car-
management.
ditis or arthritis, is secondary prevention with penicillin or
comparable agents17 to reduce the risk of future GABHS in-
Sydenham Chorea fections causing permanent cardiac valvular damage.27
Clinical Features
SC is an autoimmune disease. Chorea in isolation or accom- Chorea Symptom Suppression. This treatment is elective.
panied by other organ involvement is considered a manifes- Chorea symptom suppressing medication is effective and
tation of rheumatic disease, a group of sequelae of GABHS may be used when chorea interferes with important daily

Table 3 Differences Between Sydenham Chorea (SC) and Pediatric Autoimmune Neuropsychiatric Disorder Associated With
Streptococcal Infections (PANDAS)
Feature SC PANDAS
Prevalence Rare Controversial
Cardiac involvement Carditis/valvular disease occurs prior, during, No current evidence that this occurs; published
or after chorea if GABHS infections recur case series negative for cardiac disease
Time course and Self-limited, generally resolves in < 1 year Explosive onset/exacerbations on 2 or more
prognosis occasions, chronic symptoms may persist to a
milder degree between episodes, long-term tics
and/or OCD common
Effect of antibiotics on No suppression of symptoms reported Clinicians/families often report antibiotics directly
current neurologic or suppress the tics or OCD but no currently
psychiatric symptoms published clinical trials support this
Role of immune therapies No accepted standard Controversial
Role of antibiotics for Standard of care, until age 21 Controversial
secondary prevention
74 D.L. Gilbert

activities. Beneficial chorea suppression in SC has been de- findings, for example growth parameters or dysmorphic fea-
scribed in small case series with benzodiazepines and several tures that narrow the differential diagnosis.
anticonvulsants, most commonly valproic acid.28,29 Some The neurologic examination should be thorough, empha-
consider dopamine receptor blocking agents to be the treat- sizing portions of the examination related to basal ganglia
ment of choice, as these are usually highly effective at low and cerebellar function. Assessment of head growth, cogni-
doses.1,22,30 The expected course of treatment is brief, that is, tive function, speech, and cortical spinal tract function are
weeks to months. Therefore, long-term tardive risks are in- also important, as chronic neurologic conditions with chorea
significant. Anticholinergic agents should not be used. often involve multiple neurologic systems.
Key findings of the neurologic examination related to
Immune Modulation. This treatment is not established. On chronic choreas are discussed in Table 1.
the basis of pathophysiology of SC, it is reasonable to con-
sider immune-modulating therapies, for example, steroids or Diagnostic Approach
intravenous immuneglobulin (IVIG), to shorten the course of A constellation of neurologic and non-neurologic symptoms
illness in severe cases. The most compelling evidence for and signs can be used effectively to narrow the differential
benefit from steroids comes from a recent randomized, diagnosis. Selected diseases are discussed in Table 4.
blinded placebo-controlled study.31 Relative to placebo, a Diagnostic Testing
2-mg/kg daily oral dose of prednisone over 4 weeks, followed Neuroimaging with brain MRI is usually a diagnostic test of
by a taper, reduced the duration of chorea and accelerated the choice. Decisions about genetic and metabolic testing, par-
reduction in symptoms. Weight gain was substantial, so a ticularly for progressive, inherited diseases, can be informed
shorter treatment course may be more reasonable. Support- with on-line resource, such as on-line Mendelian inheritance
ive evidence also comes from a clinical trial comparing pred- in Man (http://www.ncbi.nlm.nih.gov/omim) and Genetests
nisone to IVIG and plasmapheresis.32 There was no placebo (http://www.genetests.org).
group in that study. Other reports from uncontrolled, retro-
spectively ascertained data are difficult to interpret. Benign Hereditary Chorea
Clinical Features
Chronic Chorea Benign hereditary chorea (BHC) is a rare, autosomal domi-
nant, static disorder characterized by onset of chorea before
Clinical Characteristics of Chronic Chorea age 5.38 Atypical clinical features are common and there is
History of Present Illness substantial overlap in phenomenology with myoclonus dys-
Most children with chronic chorea have a mixed movement tonia.39 The severity of the chorea varies substantially within
disorder secondary to a static or progressive encephalopathy. and between families.40,41 Otherwise, chorea is isolated. Fea-
In these cases, chorea is just 1, not necessarily predominant, tures supporting this diagnosis include normal general exam-
symptom. Chronic chorea may emerge gradually in infancy ination with no dysmorphic features, broadly normal intel-
but more commonly becomes apparent after age 1 year. lectual development with no regression or loss of cognitive
Children with chronic, early-onset choreas may have sub-
normal motor skills and function. In most conditions, it is
more widespread central nervous system abnormalities, and Table 4 Etiology of Chronic Chorea in Childhood: Categories
not chorea per se, that are interfering with normal neurologic and Selected Examples
function. As in Sydenham chorea, children with mature com-
Etiologic
munication and awareness should be able to describe the
Category Examples
subjective nature of the movements, that is, the movements
are involuntary, nonsuppressible, and not performed in re- Primary Benign hereditary chorea (including
sponse to an urge or sensation. However, awareness of the syndrome of choreoathetosis,
hypothyroidism, neonatal
movements on an ongoing basis may be low.
respiratory distress)
A careful developmental history is critical. Progressive loss Secondary
of skills requires a detailed evaluation to attempt to identify a Vascular/hypoxic Stroke/third trimester or pregnancy
genetic/molecular diagnosis. Although at present this will ischemic or perinatal hypoxic ischemic
most likely not have a specific treatment, precise molecular injuries leading to choreoathetoid
diagnoses give families a feeling of knowledge and more con- cerebral palsy
trol, and these may allow participation in advocacy and sup- Choreas in LeschNyhan syndrome33
port groups. Problems with learning and mood should be neurodegenerative Nonketotic hyperglycinemia34
systematically assessed as well, as these commonly co-occur. diseases and Phenylketonuria35
The presence of seizures with chorea generally indicates a severe
diffuse, serious central nervous system disease. encephalopathies
Diseases with Ceroid-lipofuscinosis36
General and Neurologic Examination chorea as a minor
Many diseases cause a relatively small number of types of or late feature
Chorea in ataxias Ataxia telangiectasia37
movement disorders. The general examination can reveal
Acute and chronic chorea in childhood 75

skills, absence of other significant neurologic disturbances, 11. PeBenito R, Talamayan RC: Fever-induced protracted ballismus in cho-
such as epilepsy, and, with the exception of chorea, normal reoathetoid cerebral palsy. Clin Pediatr (Phila) 40:49-51, 2001
12. Wong LJ, Naviaux RK, Brunetti-Pierri N, et al: Molecular and clinical
neurologic examination findings. As is often true in move-
genetics of mitochondrial diseases due to POLG mutations. Hum Mutat
ment disorders, it is important to examine other family mem- 29:E150-E172, 2008
bers in addition to taking a multigeneration history. The 13. Park S, Choi IS: Chorea following acute carbon monoxide poisoning.
presence of mild symptoms in a parent would support the Yonsei Med J 45:363-366, 2004
presence of autosomal dominant inheritance in BHC. Some 14. Gilbert DL: Drug-induced movement disorders in children. Ann N Y
symptom improvement may occur in adulthood. Acad Sci 1142:72-84, 2008
15. Isaacs KM, Kao E, Johnson MD, et al: Precipitating events and signifi-
In the absence of a family history, other diagnoses to con-
cant life stressors of pediatric patients diagnosed with a psychogenic
sider in a child presenting under age 5 with chorea include movement disorder, in 37th Annual Meeting of the International Neu-
ataxia telangiectasia (AT),37 which is autosomal recessive. ropsychological Society, Atlanta, GA, 2009
The characteristic telangiectasias lag behind the neurologic 16. Ayoub EM, Wannamaker LW: Streptococcal antibody titers in Syden-
symptoms.42 Initial diagnostic testing for a young child with hams chorea. Pediatrics 38:946-956, 1966
chorea, dystonia, or ataxia emerging between 12 and 36 17. American Academy of Pediatrics: Group A streptococcal infections, in
months of age should include serum alpha-fetoprotein, Pickering LK, Baker CJ, Long SS, et al (eds): Red Book. Report of the
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18. Maia DP, Teixeira AL Jr, Quintao Cunningham MC, et al: Obsessive
Diagnosis. MRI is usually normal.43 BHC is caused in some,
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neural transmission or structural pathology in the basal gan- and ADHD in children diagnosed with Sydenhams Chorea: A long-
glia or occasionally in other structures. The most common term follow-up of a community based sample, in American Academy of
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