Rheumatic (Sydenham) Chorea

Introduction
In 1684, Thomas Sydenham described the clinical syndrome that now bears his
name. Originally termed St. Vitus' dance, it now is referred to as rheumatic
chorea. Stoll first proposed a relationship between Sydenham chorea and
rheumatic fever (RF) in 1780.
In 1889, Cheadle described the full rheumatic syndrome of carditis, polyarthritis,
chorea, subcutaneous nodules, and erythema marginatum.
[5]
Several decades
later, epidemiologic and microbiologic studies confirmed the etiological role of
streptococcal infection in RF.
More recently, Sydenham chorea (SC) has been linked to numerous
neuropsychiatric disorders, including obsessive compulsive disorder (OCD),
attention deficit-hyperactivity disorder, depression and anxiety.
[6]

Epidemiology
Sydenham chorea is the most common cause of acquired chorea in the young.
During the latter part of the twentieth century the number of reported cases of RF
in the United States increased. This resurgence appears to be associated with
strains of group A beta hemolytic streptococcal infection that are less likely to
cause symptomatic pharyngitis.
In the United States, the incidence of RF is approximately 0.5-2 per 100,000
population per year.
The incidence of RF is clearly higher in developing countries, where the absence of
consistent and early antibiotic treatment makes RF a more endemic problem.
Chorea is a major manifestation of acute RF and is the only evidence of RF in
approximately 20% of cases.
In some outbreaks, chorea has been present in more than 30% of patients with acute
RF.
The female-to-male ratio is approximately 2:1, and most patients present between 5-
15 years of age.
Studies have demonstrated a high frequency of a positive family history in
patients with SC and rheumatic fever. Aron et al found that 3.5% of parents and
2.1% of siblings of children with SC had also been affected.
[7]

Clinical features and course
SC is a major manifestation of acute rheumatic fever.
According to the 1992 modification of the Jones criteria, chorea (or indolent carditis)
alone is sufficient for diagnosis of RF, provided other causes have been excluded.
[8]

SC typically presents with other manifestations of RF, but in 20% of cases chorea may
be the presenting or sole manifestation of RF.
The main features of SC are involuntary movements, hypotonia, and mild
muscular weakness. Chorea can be generalized or unilateral, predominantly
involving the face, hands, and arms. Movements are present at rest, aggravated
by stress, and usually cease during sleep.
Children may attempt to hide the movements with quasi-purposeful actions (such as
flinging hair back), or they may sit on their hands is an attempt to prevent these
movements.
In about 20% of patients, only one side of the body may seem to be affected
(hemichorea); however, careful examination usually reveals some involvement of the
opposite side.
The choreic movements interfere with volitional movements and result in a clumsy gait,
dropping and spilling, and explosive bursts of dysarthric speech.
o Muscular weakness leads to inability to sustain a contraction (milkmaid's grip).
o The pronator sign consists of hyperpronation of the hands, causing the palms to face
outward when the arms are held over the head. Another sign of weakness and
hypotonia is the so-called choreic handwith the arms extended, the wrist will flex
and the metacarpophalangeal joints overextend.
Some children may have such profound weakness that they appear paralyzed. Not
uncommonly, children are restricted to bed or are unable to attend school for the
duration of the illness. Fortunately, paralytic chorea is uncommon.
Patients with SC may also have psychiatric symptoms such as depression,
anxiety, personality changes, emotional lability, OCD, and attention deficit
disorder (ADD).
Whether the psychological manifestations are secondary to the movement disorder or
an integral part of the disease is not clear.
Occasionally, these symptoms precede the onset of chorea.
On average, the disease resolves spontaneously in 3-6 months and rarely lasts
longer than 1 year.
Mild chorea without functional disability may be found in a small proportion of patients
up to 10 years after the initial attack of SC.
About 20% of patients experience 2-10 recurrences, usually within 2 years after the
initial attack.
Pathophysiology
Immunology: Evidence suggests that SC may result from the production of
immunoglobin G antibodies that crossreact with antigens in the membrane of
group A streptococci and antigens in the neuronal cytoplasm of the caudate and
subthalamic nuclei, namely intracellular tubulin and extracellular
lysoganglioside.
[9]
Antineuronal antibodies have also been found in the
cerebrospinal fluid (CSF) of patients with acute rheumatic chorea.
Immunofluorescent staining has shown that sera from approximately half of the
children with SC have antibodies that react with neuronal cytoplasmic antigens in
the caudate and subthalamic nuclei.
Serum antineuronal antibody titers have been found to decrease as the chorea
improves.
In children who suffer a relapse, the increase in symptom severity correlates with a
rise in these neuronal antibodies.
Neurochemistry: The main symptoms of SC are believed to arise from an
imbalance among the dopaminergic system, intrastriatal cholinergic system, and
inhibitory gamma-aminobutyric acid (GABA) system. Evidence of this imbalance
has been suggested by the successful control of chorea by dopaminergic
antagonists and valproic acid, a drug known to enhance GABA levels in the
striatum and substantia nigra.
Neuroimaging
MRI findings in SC are not consistent and may be normal. Published
abnormalities include areas of increased signal intensity on T2-weighted images
that usually involve the basal ganglia or cerebral white matter. One study
reported an increase in basal ganglia volume consistent with localized swelling.
Follow-up studies may show improvement but some residual abnormality is
common.
[10]

Functional neuroimaging using fluorodeoxyglucose (FDG) positron emission
tomography (PET) has demonstrated reversible striatal hypermetaboli.
Diagnosis
Diagnosis of SC may be difficult, because no single, established diagnostic test
is available.
SC usually develops in those aged 3-13 years and is believed to result from a
preceding streptococcal infection. The patient may have no history of rheumatic fever,
and a preceding streptococcal infection cannot always be documented. Infections can
be subclinical and often precede the development of neurologic symptoms by age 1-6
months. At least 25% of patients with SC fail to have serologic evidence of prior
infection.
Chorea may be the first and only manifestation of rheumatic fever. However, some
patients may have subtle evidence of carditis by echocardiography despite a normal
clinical examination and ECG. Chorea alone is sufficient for diagnosis providing other
causes of the condition have been excluded.
Treatment
SC is usually self-limited, and treatment should be limited to patients with chorea
severe enough to interfere with function.
Anticonvulsants (valproic acid and carbamazepine) have been shown to be effective in
diminishing choreic movements at doses normally used for seizure control. In
particular, valproate may be quite helpful in children with SC.
Steroids have been used widely, but no controlled studies have been done to confirm
steroid efficacy in chorea.
Dopaminergic blockers (pimozide and haloperidol) are effective and, when used in
small doses, are usually well tolerated. Neuroleptics such as haloperidol and pimozide
remain an important treatment option, especially in older children. Prednisone, plasma
exchange and intravenous immunoglobulin (IVIG) have been shown to be effective.
Case reports have suggested IVIG to be a safe, effective option in disabling SC.
[11]

Parents and school officials should be informed that emotional lability is
characteristic of this organic condition.
Immunologic treatment can also be effective but is expensive and may be
associated with significant side effects.
The presence of antineuronal antibodies suggests that intravenous immunoglobulin
(IVIg) and plasma exchange may be effective.
Garvey and Swedo showed sustained improvement in 3 children treated with plasma
exchange.
[12]

Three other children treated with IVIG showed initial improvement but had recurrences
after subsequent streptococcal infection. More recent reports have shown IVIG to be
an effective safe option. Because this treatment modality is quite expensive, it should
be reserved for protracted or debilitating cases.
[11, 9]

Children with SC require prophylaxis against streptococcal infections until 18
years of age.
Previous
Next Section: Juvenile Huntington Disease
Juvenile Huntington Disease
Introduction
Huntington chorea is an autosomal-dominant, neurodegenerative disorder in
which chorea is a primary clinical manifestation. Other prominent clinical features
include progressive cognitive decline and an array of psychiatric disturbances.
The average age of onset is at 35-40 years; however, the disease has been
reported in children as young as 4 years.
The age of onset varies among families, with some showing consistently older age of
onset than others.
Age of onset among individuals of the same family also can vary widely; children of an
affected father may have a younger age of onset than children of an affected mother.
The term juvenile Huntington disease designates patients whose clinical
manifestations begin before the age of 20 years. This group also may be divided
further into those with onset before the age of 10 years and those with onset in
adolescence.
Genetics
Huntington disease (HD) is an autosomal-dominantly inherited disease with
complete penetrance. The responsible gene, IT-15, is located on the p16.3
subband of chromosome 4. The genetic mutation is an unstable, expanded DNA
trinucleotide (cytosine-adenosine-guanosine or CAG) repeat within the coding
region for a 348-kD protein named huntingtin.
All individuals possess this repeat sequence; it is the number of triplet repeats that is
significant. Patients with HD have 38 or more repeats. The earlier the age of onset, the
greater the number of repeats for a given individual.
The correlation between repeat length and rate of disease progression is unclear.
Approximately 10% of HD gene carriers develop signs of illness before age 20 years.
Between 70% and 80% of patients with childhood-onset HD have inherited the gene
from an affected father.
Note that as many as 1% of individuals with HD may have a negative test result.
Clinical features
HD in the young presents differently than in adults. Initial stages in children
include one or more of the following: mental deterioration or behavioral problems,
rigidity with gait disturbance, cerebellar dysfunction, and occasionally seizures.
Impaired ocular motility may also be an early sign of HD in the pediatric patient
and resembles oculomotor apraxia.
The patient may appear to be primarily clumsy, rather than either rigid or choreiform.
Reflexes are usually brisk, and pyramidal signs with extensor plantar responses are
common.
Seizures occur in about 30-50% of patients and are difficult to control.
Diagnosis
The availability of a DNA-based testing (to reliably identify the HD mutation)
greatly facilitates diagnosis. The ability to determine the size of the trinucleotide
repeat enables one to have accurate preclinical and prenatal diagnosis. Allele
sizes of 40 or more CAG repeats are universally associated with the HD
phenotype.
Brain MRI and CT in juvenile HD may show caudate atrophy. MRI findings also
include nonspecific increased T2 signal in the putamen. PET scanning in
symptomatic patients using radiolabeled FDG uniformly shows a marked
reduction in caudate glucose metabolism.
Presymptomatic testing should be executed only under rigid guidelines.
It should be performed only at the request of the patient.
Test results should be released only to the patient; if the result is to be released to
another party, written consent is required from the patient.
Testing minors is considered inappropriate at this time, because results may have
significant negative repercussions in raising the child.
Treatment
Presently, no specific therapy is available for HD. Management consists of
symptomatic therapy and counseling.
Some patients benefit from antidepressants; carbamazepine may be useful for mood
swings. Choline, reserpine, and dopamine antagonists may decrease choreiform
movements.
Agents such as L-dopa or dopamine agonists can be helpful in the rigid form of the
disease but may exacerbate chorea and provoke hallucinations and psychosis.
Experimental therapies (eg, agents that improve mitochondrial energy
metabolism, agents that attenuate glutamate neurotransmission and free radical
scavengers) have been ineffective.