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SD by Medscape
Choreiform movements are abrupt, irregular, and purposeless. They are brief, asymmetric,
present at rest, and may persist during sleep.
The term chorea is derived from the Greek word for dancing and was applied initially to
epidemics of dancing mania in the Middle Ages, in which large numbers of people danced
together for days.
Many such dances were described, but the most renowned was chorea Sancti Viti (St.
Vitus dance)
Sydenham used this term in his Schedula Monitoria to describe rheumatic chorea in
1686. [1, 1]
Two hundred years later, Huntington described hereditary chorea and suggested that this
movement disorder was similar to that described by Sydenham. [2]
Causes of Chorea
Inherited
Ataxia-telangiectasia
Benign hereditary chorea
Huntington disease
o Glutaric acidemia
o Propionic acidemia
o Homocystinuria
o Phenylketonuria
Mitochondrial encephalomyopathies
Neuroacanthocytosis
Paroxysmal disorders
Wilson disease
Drugs Antimetabolites
Anticholinergics
Anticonvulsants (eg, phenytoin, carbamazepine, phenobarbital)
Antihistamines
Lithium
Oral contraceptives
Endocrine
Hyperthyroidism
Chorea gravidarum
Hypoparathyroidism, pseudohypoparathyroidism
Immune/infectious
Behet disease
Other infections - Pertussis, diphtheria, varicella
Sydenham chorea
HIV related
Infectious mononucleosis
Lyme disease
Mycoplasmal pneumonia
Vascular
Arteriovenous malformation
Basal ganglia infarction or hemorrhage
Metabolic
Hypocalcemia
Hypoglycemia and hyperglycemia
Hypomagnesemia
Renal failure
Miscellaneous
Cerebral palsy
Head trauma
Neoplastic
Nutritional
Toxins
Carbon monoxide
Manganese
Organophosphate poisoning
The main neurotransmitters associated with the basal ganglia include gamma aminobutyric acid
(GABA), dopamine, acetylcholine, and glutamate. Other potentially important neurotransmitters
include enkephalin, substance P, dynorphin, cholecystokinin, and somatostatin.
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.
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
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 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).
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]
Diagnosis
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.
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.
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
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.
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.
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.
Introduction
Benign hereditary chorea (BHC) is a rare familial disorder with onset in early childhood.
Transmission is autosomal dominant with the gene locus on chromosome 14q. However, rare
cases of autosomal-recessive and X-linked inheritance have been reported.
The suggestion has been made that BHC could be allelic to HD. One family was reported to have
expanded CAG repeats, suggesting that some families with the so-called benign chorea may in
fact have a phenotypic variant of HD. More recently, mutations in the thyroid transcription
factor-1 gene on chromosome 14q have been proposed as a potential causative factor. [13]
Clinical features
Chorea usually begins around the time the child is learning to walk but may occur throughout
childhood. Most children only have chorea, which is nonprogressive and tends to diminish
during adolescence. Associated features may include delayed motor development, dysarthria,
intention tremor, athetosis, and hypotonia. Severity is highly variable but choreic movements are
typically continuous and not episodic. Intellectual function is typically normal.
Intellectual impairment has been reported in one family in which affected individuals had
intelligence quotient scores averaging 10 points lower than unaffected relatives.
Functional neuroimaging showed decreased striatal FDG metabolism in one study. Routine
imaging and EEG results are normal.
Treatment
Various drugs have been used with mixed results. Commonly used drugs include anticonvulsants
(phenytoin and carbamazepine), haloperidol, and prednisone. Dopamine antagonists appear to
have the most benefit but should be reserved for significant cases as the chorea frequently does
not require treatment.
Neuroacanthocytosis
Genetics
Clinical features
Onset usually occurs in adults aged 20-40 years but may occur before age 10. In a large British
survey of neuroacanthocytosis, the mean age for disease onset was 32 years. Death occurs
approximately 10-20 years after onset.
Chorea is the most prominent finding, but dystonia, motor and vocal tics, and Parkinson features
can also occur.
Oromandibular dystonia and orolingual dyskinesia commonly lead to dysarthria. Most patients
have difficulty eating and swallowing early in the course of the disease. Lingual-labial dyskinesia
may be so severe as to cause self-mutilation of the lips.
Axonal sensorimotor polyneuropathy with amyotrophy, elevated creatine phosphokinase (CK),
and decreased or absent deep tendon reflexes also occurs.
MRI may demonstrate atrophy of the caudate nucleus or T2-weighted hyperintensities in the
striatum.
Diagnosis
Identify characteristic clinical features, a positive family history, the presence of acanthocytes on
peripheral blood smear, and a normal plasma lipid profile.
Treatment
Treatment is symptomatic.
Antidopaminergic agents may suppress the chorea, but they may worsen concomitant
parkinsonism.
Seizures should be treated with appropriate anticonvulsants.
Wilson Disease
Wilson disease is an inborn error of copper metabolism that may present with neurologic,
hepatic, or psychiatric symptoms. It is inherited in an autosomal-recessive fashion.
In 1993, Bull et al suggested that Wilson disease is the result of a defect in the Wc1 gene
(chromosome 13q14.3-q21.1) which encodes a copper transporting P-type adenosine
triphosphatase that is expressed in the liver and kidney. [14] Excess copper accumulates in the
liver, brain, cornea, kidneys, and other tissues of untreated patients. Serum ceruloplasmin is low
and excessive copper occurs in the plasma and urine.
Clinical features
Hepatic dysfunction is the initial feature in more than 50% of cases. Patients typically develop
acute hepatitis that either resolves spontaneously or progresses to fulminant hepatic failure. Less
common presentations are asymptomatic hepatomegaly, chronic active hepatitis, or cirrhosis.
Age at onset ranges from 3 to older than 50 years. Children younger than age 10 years usually
present with hepatic failure unassociated with neurologic manifestations.
Untreated most individuals eventually develop neurologic dysfunction.
In 40% of individuals, neurologic symptoms are the presenting feature. These children typically
present during the second decade of life.
Neurologic manifestations vary widely and may include chorea as well as dystonia, tremor,
dysarthria, dysphagia, bradykinesia, and gait disorder. Most patients have gradual decline in
school performance and intellectual abilities. Seizures are uncommon.
The average age of onset in those who present with neurologic symptoms is 18.9 years.
Almost all patients with neurologic involvement also have Kaiser-Fleischer rings, which result
from deposition of copper in the Descemet membrane of the peripheral cornea.
Psychiatric manifestations include depression, personality changes, and emotional lability.
Hemolytic anemia and renal tubular acidosis also may occur.
Diagnosis
Determining hepatic copper content via liver biopsy is the single most sensitive and accurate test
for Wilson disease. Assay of serum ceruloplasmin is simple and practical, but values are normal
in 5-15% of affected patients. Other tests include the following:
Slit-lamp examination to check for the presence of corneal Kaiser-Fleischer rings is a vital part in
the diagnostic evaluation.
Twenty-four-hour urinary copper excretion rises dramatically in symptomatic patients and is a
useful test to monitor therapy.
Because of its protean manifestations, Wilson disease should be excluded in any patient who
presents with unexplained neurological dysfunction, especially if the basal ganglia or cerebellum
is involved.
Treatment
Liver transplantation
Paroxysmal Choreas
Demirkiran and Jankovic divided paroxysmal dyskinesias into 4 groups according to the
precipitating circumstances. [15]
These choreas consist of any combination of these paroxysmal attacks: dystonia, chorea,
athetosis, and ballismus. Goodenough et al noted choreoathetosis in 64% of patients. [16] The age
of onset ranges from 6-15 years. The attacks typically last less than 1 minute but occur frequently
(more than 100 times per day).
The extremities are affected primarily, but facial, neck, and trunk muscles also can be affected.
The attacks may be disabling and interfere with walking, working, and daily activities.
About half of the reported cases are familial, with both autosomal-dominant and -recessive
patterns of inheritance. Multiple sclerosis, head trauma, thalamic infarcts, hypoparathyroidism,
hypernatremia, and hyperglycemia represent common causes of secondary paroxysmal
kinesiogenic dyskinesia.
Phenytoin has been considered the drug of choice and generally is used in dosages similar to
those used in epilepsy; however, it also has been shown to be effective in smaller doses.
Satisfactory response has been obtained with other anticonvulsants, particularly carbamazepine;
acetazolamide also may be used.
The attacks occur spontaneously without any specific precipitant. The duration ranges from 2-3
minutes to 4 hours, a major feature that differentiates it from paroxysmal kinesiogenic
dyskinesia.
In one series, 81% of cases were familial. Multiple sclerosis is the leading cause of secondary
paroxysmal nonkinesiogenic dyskinesia. Other causes include encephalitis, hypoparathyroidism,
thyrotoxicosis, head injury, basal ganglia calcification, AIDS, and Leigh syndrome.
Attacks of paroxysmal nonkinesiogenic dyskinesia may diminish with age in frequency and
severity.
It is more difficult to treat than paroxysmal kinesiogenic dyskinesia, since the nonkinesiogenic
form does not respond to anticonvulsant drugs. Clonazepam (1-2 mg/d) appears to be the drug of
choice; phenobarbital and valproic acid also may be effective.
This disorder consists of attacks of dystonia, sometimes combined with chorea and athetosis, that
are triggered by exertion such as walking or running. The attacks usually involve the lower limbs
and are often bilateral. They may last from a few minutes to 30 minutes. Most of the described
cases suggest an autosomal-dominant mode of inheritance. Treatment with anticonvulsants and
levodopa has proven unsatisfactory.
Haloperidol
Pimozide
Dopaminergic depletors
Tetrabenazine
Reserpine
Benzodiazepines
Clonazepam
Diazepam
Anticonvulsants
Phenytoin
Carbamazepine
Valproic acid
Antidopaminergic agents
o Haloperidol should be started at a low dose (0.5-2 mg/d). Dose may be titrated gradually
for a satisfactory response.
Aside from tardive dyskinesia, side effects include sedation, cognitive impairment, akathisia,
acute dystonic reactions, and parkinsonism.
o Pimozide (usually 0.2 mg/kg/d) may be associated with fewer side effects.
o Baseline and follow-up ECGs are recommended to monitor for Q-T prolongation.
Tetrabenazine, a presynaptic dopamine depletor, also may be effective. It does not produce
tardive dyskinesia, but side effects include depression, orthostatic hypotension, weight gain, and
drowsiness.
Benzodiazepines such as clonazepam and diazepam may be used to treat chorea, particularly in
the early stages. Sedation is a major concern. They may be useful in the first few days until a
satisfactory response to other drugs is achieved.
In one study, 15 children with SC were treated with sodium valproate (15-20 mg/kg/d) for a
mean duration of 19.2 months. In 13 of the children, the choreiform movements disappeared
within 1 week of beginning therapy.
Source: http://emedicine.medscape.com/article/1181993-overview