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Background:
The term chorea comes from the Latin word choreus, which means dancing.
Chorea has been defined by the ad hoc Committee on Classification of the
World Federation of Neurology as "a state of excessive, spontaneous movements,
irregularly timed, non-repetitive, randomly distributed and abrupt in character.
These movements may vary in severity from restlessness with mild intermittent
exaggeration of gesture and expression, fidgeting movements of the hands,
unstable dance-like gait to a continuous flow of disabling, violent movements."
Chorea involves proximal as well as distal muscles. In most patients, normal tone is
noted, but in some instances, hypotonia is present. In a busy movement disorder
center, levodopa-induced chorea is the most common movement disorder, followed by Huntington disease (HD).
Ballism, derived from the Greek word meaning "to throw," has been defined as
"continuous, violent, coordinated involuntary activity involving the axial and proximal
appendicular musculature such that the limbs are flung about." This movement disorder most often involves only one side of the body (ie, hemiballism[us]).
Occasionally, bilateral movements occur (ie, biballism or paraballism). Many patients
with hemiballism have chorei-form movements and vice versa, and hemiballism often evolves into hemi-chorea. Currently, ballism should be viewed as a severe form of chorea.
Pathophysiology:
A simple model of basal ganglia function states that dopaminergic and GABAergic
impulses from the substantia nigra and motor cortex, respectively, are funneled
through the pallidum into the motor thalamus and motor cortex. These impulses are modulated in the striatum via 2 segregated, parallel, direct and indirect loops through the medial pallidum and lateral pallidum/subthalamic nucleus.
Subthalamic nucleus activity drives the medial pallidum
to inhibit cortex-mediated impulses, thereby inducing parkinsonism. Absent subthalamic
nucleus inhibition enhances motor activity
through the motor thalamus, resulting in abnormal involuntary movements such as
dystonia, chorea, and tics. A classical example of loss of subthalamic inhibitory drive
is ballism.
The choreatic syndrome that has been studied the most is Huntington
chorea;
therefore, the pathophysiology of HD as it applies to chorea will be the focus of the
discussion that follows.
Dopaminergic mechanism
In Huntington chorea, the content of striatal dopamine is normal,
indicating that the major pathological alterations lay in the surviving, but diseased,
medium-sized, spiny, striatal dopaminergic neurons.
Pharmacologic agents that either deplete dopamine (eg, reserpine,
tetrabenazine) or block dopamine receptors (eg, neuroleptic medications) improve chorea,
giving further support to this observation. Since drugs that decrease the striatal content
of dopamine improve chorea, increasing the amount of dopamine worsens chorea, such as
the levodopa-induced chorea seen in Parkinson disease (PD).
Cholinergic mechanism
The concept that a critical striatal balance between acetylcholine (Ach) and dopamine
is essential for normal striatal function received its greatest acceptance in the understanding
of PD. In the early phases of PD, anticholinergic medications are used commonly, especially
when tremor is the predominant symptom. Other PD symptoms, such as bradykinesia and rigidity, may improve as well.
Development of chorea in patients treated with anticholinergic medications such as
trihexyphenidyl is a common clinical observation. Furthermore, intravenous administration
of physostigmine (a centrally acting anticholinesterase) can reduce chorea temporarily.
Similarly, anticholinergic-induced chorea can be overcome promptly by administration
of
physostigmine.
In the basal ganglia of patients with HD is a patchy reduction of choline acetyltransferase,
the enzyme that catalyzes the synthesis of ACh. A marked reduction of muscarinic cholinergic receptor sites also has been reported. These 2 observations could explain the
variability of the response to physo-stigmine and
the limited efficacy of Ach precursors, such as choline and lecithin.
Serotonergic mechanism
Manipulation of striatal serotonin may play a role in the genesis of many abnormal movements.
Selective serotonin reuptake inhibitors such as fluoxetine may induce or aggravate parkinsonism, akinesia, myoclonus, or tremor. The role of serotonin (5-hydroxytriptamine [5-HT]) in choreiform movements is less clear.
The striatum has a relatively high concentration
of serotonin. Pharmacologic attempts to either stimulate or inhibit serotonin receptors
in Huntington chorea have shown no effect, indicating that
the contribution of serotonin in the patho-genesis of chorea is limited.
GABAergic mechanism
The most consistent biochemical lesion in Huntington chorea
appears to be a loss of
neurons in the basal ganglia that synthesize and contain GABA. The significance of this
remains unknown. A variety of pharmacologic techniques to increase CNS GABA levels have been attempted; however, no benefits have been obtained.
Substance P and somatostatin
Substance P has been shown to be markedly decreased in HD,
while somatostatin is increased. The significance of this remains unknown.
Ballism
This movement disorder usually involves only one side of the body (ie, hemiballism).
Hemiballism usually is attributed to lesions of the contralateral subthalamic nucleus,
although infarction in the caudate, striatum, lenticular nucleus, or thalamus also has
been associated with hemiballism.
Lesions of the subthalamic nucleus cause contralateral hemiballism-hemichorea by
reducing the normal excitatory drive from the subthalamic nucleus to the internal segment
of the globus pallidus.
This reduces the inhibitory output of the globus pallidus on the thalamus, and this disinhibitiongives rise to excessive excitatory drive to the cortex,
which is expressed as contralateral hyperkinetic movements. However, this disorder often appears in the absence of a lesion in the subthalamic nucleus.
Klawans et al suggested that increased dopaminergic transmission might play a role in
the pathophysiology of this disorder. This hypothesis is supported by the observation
that dopamine-receptor blockers and catecholamine-depleting agents often improve hemiballism.
While hemiballism and hemichorea are distinguishable on the basis of type
and distribution of movements, they represent 2 different symptoms on a spectrum of the same disease process. Why one patient with basal ganglia dysfunction
develops hemiballism and another with similar pathologic change develops hemichorea
is unknown.
Frequency:
In the US: Although
no data are available regarding the incidence of chorea, the incidence of several entities in which chorea is the main clinical
feature is well known.
- HD is an autosomal dominant, neurodegenerative disorder in
which
the defective gene is located on the short arm of chromosome 4. The estimated prevalence of HD in the United States
is 5-10 per 100,000 people.
- Wilson disease is an autosomal recessive, multisystem disease
with a gene linked to
the esterase D locus on chromosome 13. Although the gene prevalence (heterozygous carriers who inherited only 1 abnormal gene)
has been estimated to be as high as 1%, the disease prevalence is only 30 per 1,000,000.
- Benign hereditary chorea, a fairly rare disorder in which most of
the pedigrees have
clearly demonstrated dominant inheritance, has an incidence of approximately 1 per 500,000.
Race:
-
George Huntington first described Huntington disease ransmission in 1872 in successive generations of natives of
Long Island, New York. All affected individuals descended from ancestors who had
emigrated from East Anglia to the New World in 1649. This disorder now is
dispersed widely around the globe.
-
HD is best known in Caucasian populations. All cases of the disorder have probably occurred from the lineage originating
in East Anglia.
Age:
-
Chorea may commence at any age. In children, postpump chorea
and infectious, inflammatory, and striatal lesions may account for many cases.
-
About 10% of patients with HD have onset of the disease when they are younger than 20 years, about 6% when they are
younger than 21 years, and about 3% when they are
younger than 15 years, but the typical peak age at onset is
in the fourth and fifth decades of life.
-
Cases have been recognized in patients younger than
5 years. Patients with early onset usually inherited the disease from their father,
while patients with later onset are more likely to have inherited the gene from their mother. The relatively low rate of expression in childhood
is succeeded by a virtual exponential upsweep in
the rate of appearance through the second and third decades of life to reach a plateau that is sustained from the fourth to the seventh
decades. Although 27% of cases are first recognized in patients older than 50 years,
most of the cases are
documented in patients younger than 60 years. Onset has been
recorded as late as the eighth decade.
-
Neuroacanthocytosis, perhaps the most common form of hereditary
chorea, usually manifests clinically in the third and fourth decade (range is 8-62 years).
It should be
differentiated from late-onset HD through careful pedigree
analysis and neurogenetic testing.
-
Senile chorea is a condition that manifests gradually in late
middle life.
-
In general, on the basis of age of onset, benign hereditary chorea may be divided into 3 types: (1) early infancy, (2) at about 1 year
of age, and (3) during late childhood or
adolescence. The most common age of onset is about 1 year, when the child begins to walk.
History:
Patients suffering from chorea may not be initially aware of the abnormal movements, as the abnormalities may be subtle.
Patients can suppress the chorea temporarily and
frequently "camouflage" some of the movements by incorporating them into semipurposeful
activities (ie, parakinesia).
The inability to maintain voluntary contraction (ie,
motor impersistence), as seen during manual grip (milkmaid grip) tests or tongue protrusion,
is a character-istic feature of chorea and results in dropping objects and clumsiness.
Muscle stretch reflexes are often "hung-up" and pendular.
In severely affected patients, a peculiar dancelike gait may be noted. Depending on the
underlying cause of the chorea, other motor symptoms include dysarthria, dysphagia,
postural instability, ataxia, dystonia, and myoclonus. A brief discussion of the clinical
manifestations of the most common choreatic diseases is presented here.
Huntington disease
-
Penetrance of HD is 100%. Expression is highly variable, both
with respect to clinical manifestations and age of onset.
When the disorder emerges early, particularly in patients younger than 20 years, it
is most likely to run a rapid course with grave disability due to cognitive decline.
- Psychological disturbances and personality change are the
initial manifestations in over 50% of affected persons. Symptoms consistent with a depressive
state are the most frequent.
- Duration of illness from onset to death is about 15 years in the case of adult HD and 8-10 years for the juvenile variant.
Wilson disease
-
The clinical features are age dependent. In children,
the disease is manifested initially by progressive dystonia,
rigidity and dysarthria, and hepatic dysfunction, whereas in adults psychiatric symptoms,
tremor, and
dysarthria usually predominate |
Wilson's Disease continued
- Since Kayser-Fleischer
rings are almost always present when neurological symptoms are present, slit-lamp examination of the cornea needs to be carried out to be certain
that Wilson disease is excluded in a patient with chorea beginning in childhood or young
adulthood.
In patients with chorea and a negative slit-lamp examination, serum copper and ceruloplasmin along with a 24-hour
copper urine excretion need to be measured
Neuroacanthocytosis
Symptoms usually begin with lip and tongue biting (often
causing self-injury), orolingual dystonia, motor and phonic tics, generalized chorea,
parkinsonism, and seizures. Patients with neuro-acanthocytosis
may report inability to feed themselves because of dystonic
tongue protrusion every time they wish to
eat.
Other features include cognitive and personality changes, dysphagia, dysarthria, amyotrophy, areflexia, evidence of axonal neuropathy
with absent deep ankle tendon stretch reflexes, and elevated serum creatine kinase without evidence of myopathy.
Senile chorea:
This clinical entity is characterized by gradual onset of generalized and symmetric chorea with slow progression
and specifically excluding mental deterioration, emotional disturbances, or family history; therefore, neurogenetic
testing (CAG repeat) should be performed.
Sydenham chorea
Sydenham chorea is a major manifestation of acute rheumatic fever.
With the 1992 modifications of the Jones criteria, it alone
is sufficient to enable the physician to make the diagnosis
of the first attack of acute rheumatic fever. It is considered a
disease of childhood; however, it also may be seen in
adults. Rheumatic chorea is characterized by muscle weakness and the
presence of chorea. The patients have the milkman grip
sign, clumsy gait, and explosive bursts of dysarthric speech.
Psychological symptoms are equally prominent and
typically precede the appearance of even the most subtle choreiform movements. Emotional lability is the most common symptom; decreased attention span,
obsessive-compulsive symptoms, and separation anxiety disorder also are seen. Symptoms
can lag behind the etiologic streptococcal infection by 1-6 months. In adults, generalized
poststreptococcal chorea may complicate birth control
pills or pregnancy (chorea gravidarum).
Benign hereditary chorea
This is a rare autosomal dominant
genetic disorder characterized by non-progressive choreiform movements appearing in childhood,
without intellectual impairment. It is further distinguished clinically from juvenile HD by the
absence of seizures, rigidity, or cerebellar features.
It does not shorten the life span of affected patients
but severely affected patients can be severely disabled by the chorea.
Physical:
Since
HD is the most clearly defined choreatic disease, its physical findings
are described here.
Huntington disease
-
Neurobehavioral changes typically consist of personality changes,
apathy, social withdrawal, agitation, impulsiveness,
depression, mania, paranoia, delusions, hostility, hallucinations,
or psychosis.
-
The "Westphal variant" is dominated by rigidity,bradykinesia,
and dystonic postures. Generalized seizures and myoclonus may be seen.
- Ataxia and dementia are also present.
Causes:
Idiopathic - Physiological chorea of infancy,
buccal-oral-lingual dyskinesia,
senile chorea
Hereditary
HD, hereditary nonprogressive chorea (benign hereditary chorea),
benign
recessively inherited choreo-athetosis of early onset, familial inverted chorea, neuroacanthocytosis, familial remitting chorea, nystagmus and cataracts, ataxia-telangiectasia, tuberous sclerosis, familial calcification of
basal ganglia, Hallevorden-Spatz disease, Friedreich ataxia
Hereditary (metabolic)
Wilson disease, glutaric aciduria, Lesch-Nyhan disease, phenylketonuria, acute intermittent porphyria, propionic acidemia, abetalipoproteinemia, lipid storage diseases
Other metabolic and endocrine disorders
Kernicterus, hyperthyroidism hypo-parathyroidism, hypoglycemia, nonketotic
hyperglycemia, chorea gravidarum, hypo-magnesemia, chronic nonfamilial hepatic encephalopathy, anoxic encephalopathy (including postcardiac transplantation),
post-portocaval anastomosis for portal hypertension
Paroxysmal
Paroxysmal kinesogenic choreoathetosis, paroxysmal dystonic choreoathetosis
Infectious
- Sydenham chorea, encepha-litides, subacute sclerosing panencephalitis, syphilis, enteric
cytopathogenic human orphan (ECHO) virus, Lyme disease, HIV infection, cerebral toxoplasmosis,
Creutzfeldt-Jakob disease, subacute bacterial endocarditis
Drug induced
Neuroleptics, levodopa, anticholinergics, oral contraceptives, antihistamines,
amphetamines, cocaine, phenytoin, tricyclics,
Toxins
Alcohol intoxication and withdrawal, carbon monoxide, manganese, mercury
Vascular
Cerebrovascular disease (ischemic or hemorrhagic), chronic subdural hematoma, Moyamoya disease, migraine/hemicrania choreatica, Churg-Strauss syndrome, polycythemia vera
Immunologic
Systemic lupus erythematosus, primary antiphospholipid antibody syndrome,
multiple sclerosis, postcardiac transplantation, postvaccination
Tumors - Primary, metastatic
Miscellaneous - Mitochondrial cytopathies,
ventriculoperitoneal shunts
DIFFERENTIALS
Chorea Gravidarum
Huntington Disease
Neuroacanthocytosis
Neuroacanthocytosis
Syndromes
Wilson Disease
WORK UP
Lab Studies:
The diagnosis of the primary choreatic conditions is based on history and
clinical findings; however, several laboratory studies are useful, especially
in distinguishing the secondary forms of chorea from the primary forms. Some of them are mentioned here.
Huntington disease:
The only laboratory study presently available to confirm HD is genetic testing.
It identifies a gene abnormality in the short arm of chromosome 4, characterized by abnormal repetition of the trinucleotide CAG, the length of which
determines the age of onset (anticipation).
Wilson disease:
A low serum ceruloplasmin level and serum copper with increased urinary copper excretion corroborate the diagnosis in most cases. Persistent aminoaciduria,
reflecting a renal tubular abnormality, is present in most but not all patients. Liver function test results are usually abnormal. Serum ammonia may be elevated. If diagnosis is still uncertain, liver biopsy will help confirm the diagnosis.
Sydenham chorea:
The chorea can lag behind the etiologic streptococcal infection by 1-6 months,
sometimes as long as 30 years; therefore, antistreptococcal antibody titers may
no longer be elevated at presentation. Without documentation of an antecedent
streptococcal infection, the diagnosis of Sydenham chorea must be made by
excluding other causes.
Neuroacanthocytosis:
The diagnosis is confirmed by the presence of spiky erythrocytes (acanthocytes)
in peripheral blood smears. The serum creatine kinase may be elevated.
Other laboratory studies
useful in the differential diagnosis of chorea include complement
levels, antinuclear antibody (ANA) titers, antiphospholipid antibody titers, amino acids
in serum and urine, enzymatic studies from skin fibroblasts, thyroid-stimulating hormone
(TSH), thyroxine (T4), and parathormone (PTH).
Imaging Studies:
MRI
Patients with HD and choreo-acanthocytosis show decreased signal in the neostriatum, caudate, and putamen. No significant difference
has been observed between these diseases. The decreased neostriatal signal corresponds
to increased iron deposition.
Generalized atrophy, as well as focal atrophy of the neostriatum, predominantly of the caudate, with resulting enlargement of the frontal horns,
follows the initial findings of decreased neostriatal signal.
Most cases of Sydenham chorea show no abnormalities. However, a study reported volumetric differences in the caudate, putamen, and globus
pallidus; they were significantly larger in patients with
Sydenham chorea than in controls.
Patients with hemiballismus
demonstrate signal changes in the contralateral subthalamic nucleus or, less often, the striatum or thalamic nuclei.
MRI of the brain of patients with senile chorea shows a decrease in signal intensity throughout the striatum (suggesting iron deposition) and
narrowing of the space separating the caudate head and putamen,
but no overt atrophy of these structures.
Positron emission tomography
Fluorodopa (F-dopa) uptake is normal or mildly reduced in patients with chorea. HD and choreo-acanthocytosis show bilateral
hypometabolism in the caudate nucleus and putamen.
Patients with chorea and dementia show decreased glucose metabolism
in the frontal, temporal, and parietal cortices.
Patients with benign hereditary chorea may or may not show decreased metabolism in the caudate.
The finding of normal cerebral glucose metabolism in the striatal
region practically rules out HD, this being a useful
tool for differential diagnosis. The definite diagnosis of HD
is made easily by neurogenetics.
Hypometabolism in the caudate nucleus and putamen on the contralateral
side is seen in patients with hemichorea.
TREATMENT
Medical Care:
- Only symptomatic treatment is available for patients with chorea.
Chorea may be a disabling symptom, leading to bruises, fractures, and falls, and impairing the ability of patients to feed themselves. In addition,
patients sometimes express a desire for antichorea treatment for cosmetic reasons.
-
The most widely used agents in treatment of chorea are the
neuroleptics. The basis of their mechanism of action is thought to
be related to blocking of dopamine receptors. Neuroleptics can be classified as typical and atypical.
-
Typical neuroleptics include
haloperidol and fluphenazine. Atypical neuroleptics include risperidone, olanzapine, clozapine, and quetiapine. Dopamine-depleting agents, such
as reserpine and tetrabenazine, represent another option in the treatment of chorea.
-
Reports of drug treatment in hemiballism must take into account the high spontaneous remission rate of the disorder. Anecdotal reports
must be viewed with caution, unless they can demonstrate that the
response is due to the agent (by recurrence of the movements with
drug withdrawal). The rarity of this disorder and the severity of its
manifestations have precluded placebo-controlled drug trials.
Pharmacologic treatment is the same as that prescribed for other
choreatic disorder
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MEDICATION
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Drug Category: Antipsychotic agents
These agents block dopamine receptors and appear to have antispasmodic
effects.
Drug Name
|
Haloperidol (Haldol) -- Useful in treatment of irregular spasmodic
movements of limbs or facial muscles.
|
| Adult Dose |
Initial doses should be low: 0.5-1 mg/d PO; doses >10 mg/d
have yielded little or no increased benefit over lower doses
|
| Pediatric Dose |
Not established
|
| Contraindications |
Documented hypersensitivity; narrow-angle glaucoma; bone marrow
suppression; severe cardiac or liver disease; severe hypotension; subcortical brain damage
|
| Interactions |
May increase serum concentrations of TCAs and hypotensive
action of antihypertensive agents; phenobarbital or carbamazepine may decrease effects; anticholinergics may increase intraocular
pressure; lithium may cause encephalopathy-like syndrome
|
| Pregnancy |
C - Safety for use during pregnancy has not been established.
|
| Precautions |
Patients may experience extrapyramidal symptoms, such as rigidity,
akinesia, acute dystonic reactions, tardive dyskinesia, and neuroleptic malignant syndrome; less likely than other antipsychotic
agents to cause sedation and hypotension |
Drug Name
|
Fluphenazine (Prolixin) -- Blocks postsynaptic mesolimbic
dopaminergic D1 and D2 receptors in brain. Exhibits strong alpha-adrenergic and anticholinergic effects. May depress reticular
activating system.
|
| Adult Dose |
0.5-1 mg/d PO initially
|
| Pediatric Dose |
Not established
|
| Contraindications |
Documented hypersensitivity; narrow-angle glaucoma
|
| Interactions |
May potentiate effects of narcotics, including respiratory
depression; lithium increases CNS effects; barbiturates may decrease effects
|
| Pregnancy |
C - Safety for use during pregnancy has not been established.
|
| Precautions |
Besides extrapyramidal symptoms as described for haloperidol,
mild leukocytosis, leukopenia, and eosinophilia occasionally occur; dermatological reactions are common; watch for urinary
retention, blurred vision, dry mouth, and constipation as result of anticholinergic effects |
Drug Name
|
Clozapine (Clozaril) -- New atypical neuroleptic medication
available in 25 mg and 100 mg tablets. Blocks norepinephrine, serotonergic, cholinergic, histamine, and dopaminergic receptors.
Mechanism of action still unclear. Affinity for mesolimbic D4 dopamine receptor ~~~~~~~~ for striking effects in control of
behavioral and psychiatric symptoms with low incidence of extrapyramidal symptoms. Histamine receptor blockade ~~~~~~~~ for
increased incidence of sleep disturbances.
|
| Adult Dose |
Chorea: 12.5 mg PO qd; increase dose weekly to 50-75 mg PO
qd
Dystonia: Doses of up to 700 mg/d may be needed
PD: 25-50 mg PO qd required to control hallucinations
Schizophrenia:
Higher doses required
|
| Pediatric Dose |
Not established
|
| Contraindications |
Documented hypersensitivity; history of agranulocytosis; history
of pulmonary embolism, diabetes mellitus, hepatitis, narrow-angle glaucoma, bladder retention, prostate enlargement
|
| Interactions |
Epinephrine and phenytoin may decrease effects; other dopamine-depleting
agents, TCAs, neuroleptics, CNS depressants, guanabenz, and anticholinergics may increase effects
|
| Pregnancy |
C - Safety for use during pregnancy has not been established.
|
| Precautions |
Monitor for agranulocytosis and orthostatic hypotension; caution
in patients who take other drugs that can cause agranulocytosis, such as carbamazepine and ticlopidine; all patients should
undergo weekly WBC counts with differential; if WBC falls below 3000/mm3 or if absolute neutrophil count falls
below 1500/mm3, clozapine therapy should be interrupted or discontinued; anticholinergic reactions can be quite
severe; may cause pulmonary embolism or hepatitis; may elevate LFTs |
Drug Name
|
Olanzapine (Zyprexa) -- May inhibit serotonin, muscarinic,
and dopamine effects.
|
| Adult Dose |
5-10 mg qd PO initially; increase to 10 mg PO qd within 5-7
d; not to exceed 20 mg/d
|
| Pediatric Dose |
Not established
|
| Contraindications |
Documented hypersensitivity
|
| Interactions |
Fluvoxamine may increase effects; antihypertensives may increase
risk of hypotension and orthostatic hypotension; levodopa, pergolide, bromocriptine, charcoal, carbamazepine, omeprazole,
rifampin, and cigarette smoking may decrease effects
|
| Pregnancy |
C - Safety for use during pregnancy has not been established.
|
| Precautions |
Agranulocytosis has not been reported to date; watch for orthostatic
hypotension and constipation; less risk of extrapyramidal effects than traditional neuroleptics; serum half-life increases
by about 50% in patients older than 65 years and can be expected to increase in patients with liver dysfunction; both patient
groups may require smaller than average dosages |
Drug Name
|
Risperidone (Risperdal) -- Binds to dopamine D2-receptor with
20 times lower affinity than for 5-HT2 receptor. Improves negative symptoms of psychoses and reduces incidence of extrapyramidal
adverse effects.
|
| Adult Dose |
1 mg PO bid initially; increase slowly to 4-6 mg/d
|
| Pediatric Dose |
Not established
|
| Contraindications |
Documented hypersensitivity
|
| Interactions |
Carbamazepine may decrease effects; may inhibit effects of
levodopa; clozapine may increase levels
|
| Pregnancy |
C - Safety for use during pregnancy has not been established.
|
| Precautions |
Low risk of extrapyramidal adverse effects; may cause extrapyramidal
reactions, hypotension, tachycardia, and arrhythmias |
Drug Name
|
Quetiapine (Seroquel) -- May act by antagonizing dopamine
and serotonin effects.
|
| Adult Dose |
25 mg PO bid initially; titrate slowly to effect in 2-3 divided
doses; not to exceed 800 mg/d
|
| Pediatric Dose |
Not established
|
| Contraindications |
Documented hypersensitivity
|
| Interactions |
May antagonize levodopa and dopamine agonists; phenytoin,
thioridazine, and other liver enzyme inducers may reduce levels
|
| Pregnancy |
C - Safety for use during pregnancy has not been established.
|
| Precautions |
May induce orthostatic hypotension associated with dizziness,
tachycardia, and syncope; neuroleptic malignant syndrome has been associated with this treatment |
Drug Category: Dopamine depleting agents
These agents deplete the central nervous system of dopamine,
thereby reducing chorea.
Drug Name
|
Reserpine (Serpasil) -- Depletes norepinephrine and epinephrine,
which in turn depress sympathetic nerve functions.
|
| Adult Dose |
0.5 mg PO qd; titrate to 1.0 mg PO qd
|
| Pediatric Dose |
Not recommended
|
| Contraindications |
Documented hypersensitivity; diagnosed mental depression
|
| Interactions |
Tricyclic antidepressants may decrease antihypertensive effects;
either digitalis or quinidine may increase risk of cardiac arrhythmia
|
| Pregnancy |
C - Safety for use during pregnancy has not been established.
|
| Precautions |
Sedation and inability to concentrate or perform complex tasks
are most common adverse effects; occasional psychotic depression may occur that can lead to suicide (usually appears insidiously
over many weeks or months and may not be attributed to drug because of delayed and gradual onset of symptoms); must be discontinued
at first sign of depression; do not give to patients with history of depression; other adverse effects include nasal stuffiness
and exacerbation of peptic ulcer disease; orthostatic hypotension may occur but does not usually cause symptoms; parkinsonism
may present as adverse effect |
Drug Name
|
Tetrabenazine (Nitoman) -- Dopamine-depleting agent available
worldwide except in United States. Works by depleting dopamine in presynaptic neuron and by blocking postsynaptic dopamine
receptor.
|
| Adult Dose |
25 mg PO qd initially; increase dose according to clinical
response and adverse effects
|
| Pediatric Dose |
Not established
|
| Contraindications |
Documented hypersensitivity; depression
|
| Interactions |
Potentiates effects of other dopamine-depleting agents (ie,
reserpine) and of dopamine-blocking agents such as neuroleptics
|
| Pregnancy |
X - Contraindicated in pregnancy
|
| Precautions |
See contraindications; patients may develop sedation, anxiety,
akathisia, confusion, tremor, and dizziness; should use caution in orthostatic and drug-induced hypotension; because tetrabenazine
depletes dopamine, tends to worsen symptoms of parkinsonism/Parkinson disease or drug-induced parkinsonism |
Drug Category: Benzodiazepines
That these agents reduce GABA concentrations in the caudate,
putamen, substantia nigra, and globus pallidus has been
demonstrated. By analogy, increased GABA activity might ameliorate
chorea.
Drug Name
|
Clonazepam (Klonopin, Rivotril) -- Developed as antiepileptic,
hypnotic, and anxiolytic used as adjunct for treatment of chorea. Belongs to benzodiazepine group, increasing GABAergic transmission
in CNS. Reaches peak plasma concentration at 2-4 h after oral or rectal administration.
|
| Adult Dose |
0.5 mg PO qd; increase dose weekly according to need and response
|
| Pediatric Dose |
Not established
|
| Contraindications |
Documented hypersensitivity; severe liver disease; acute narrow-angle
glaucoma
|
| Interactions |
Phenytoin and barbiturates may reduce effects; CNS depressants
increase toxicity
|
| Pregnancy |
C - Safety for use during pregnancy has not been established.
|
| Precautions |
Caution in chronic respiratory disease or impaired renal function;
withdrawal symptoms can result from abrupt discontinuation of medication; main adverse effects include sedation, tolerance,
ataxia, depression, and confusion | |
|
FOLLOW UP
Complications:
Some patients may develop rhabdomyolysis or local trauma due
to the severity of the abnormal involuntary movements.
Aspiration pneumonia may result in early death in some patients with neuro-acanthocytosis owing to the swallowing difficulties and tongue
dystonia usually present in these patients. |
Prognosis:
Prognosis depends on the cause of the chorea. HD has a poor
prognosis, as all patients will die of complications of the disease.
Similarly, patients with neuro-acanthocytosis may develop aspiration pneumonia resulting in early death.
~~
eMedicine Journal, July 12 2001, Volume 2, Number 7 See BIBLIOGRAPHY
Authored by Maria Alejandra Herrera, MD, Fellow, Department of Neurology,
The Cleveland Clinic Florida Coauthored by Nestor Galvez-Jimenez, MD,
Program Director, Associate Professor, Department of Neurology, Division of
Medicine, Cleveland Clinic
Florida
eMedicine
Journal, July 12 2001, Volume 2, Number 7
See URL for BIBLIOGRAPHY |
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