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pathways, respectively
Pathophysiology
MRI
Patients with Huntington disease (HD) and chorea-
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
Medical Care
Endocrine
Hyperthyroidism
Chorea gravidarum
Hypoparathyroidism, pseudohypoparathyroidism
Immune/infectious
Behet disease
Other infections - Pertussis, diphtheria, varicella
Primary antiphospholipid antibody syndrome
Sydenham chorea
Systemic lupus erythematosus
Bacterial endocarditis
Herpes simplex encephalitis
HIV related
Infectious mononucleosis
Lyme disease
Mycoplasmal pneumonia
Viral meningoencephalitis (eg, mumps, measles, varicella)
Vascular
Arteriovenous malformation
Basal ganglia infarction or hemorrhage
In some outbreaks, chorea has been present in more than 30% of patients
with acute RF.
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.
Neuroimaging
Background
Willson and Preece (1932) found that the overall incidence of chorea
gravidarum was approximately 1 case per 300 deliveries. The
condition is much more rare now.
The decline is probably the result of a decline in rheumatic
fever (RF), which was a major cause of chorea gravidarum before
the use of antibiotics for streptococcal pharyngitis.
In general, about half the cases are idiopathic, with rheumatic fever
and antiphospholipid syndrome (APLS) underlying most of the
remainder.
Patient profile
Willson and Preece noted that nearly 70% of their patients gave a
previous history of either rheumatic fever or chorea.
Of patients who present with chorea and no apparent
carditis, 20% may develop rheumatic heart disease after 20 years.
Interestingly, 50% of patients with oral contraceptive-
induced chorea have a past history of chorea, which in 41% of
cases is of rheumatic origin.
Background
is an incurable,
adult-onset,
autosomal dominant inherited disorder associated with
cell loss within a specific subset of neurons in the basal
ganglia and cortex.
HD is named after George Huntington, the physician who described it as
hereditary chorea in 1872.
Characteristic features of HD include
involuntary movements, dementia, and behavioral changes.
Pathophysiology
International
The prevalence in most European countries ranges from
1.63-9.95 per 100,000 people. The prevalence of HD in
Finland and Japan is less than 1 per 100,000 people.
Mortality/Morbidity
The normal estimated total body copper content is 50-100 mg, and the
average daily intake 2-5 mg, depending on an individuals intake of
legumes, meats, shellfish, and chocolate.
Copper is an important component of several metabolic enzymes, including
lysyl oxidase, cytochrome c oxidase, superoxide dismutase, and dopamine
beta-hydroxylase.
Age-related presentations
Kayser-Fleischer rings
Approach Considerations
Abdominal imaging
Computed tomography (CT) scanning, magnetic resonance imaging (MRI),
ultrasonography, and nuclear medicine studies of the liver have been
uninformative, with findings neither specific nor sensitive for Wilson disease.
Electrocardiography
Resting electrocardiographic abnormalities include left ventricular or
biventricular hypertrophy, early repolarization, ST segment depression, T-
wave inversion, and various arrhythmias.
Serum Ceruloplasmin
A characteristic "face of the giant panda" sign has been described, formed
by high signal intensity in the tegmentum (except for the red nucleus),
preserved signal intensity of the lateral portion of the pars reticulata of the
substantia nigra, and hypointensity of the superior colliculus.
PET Scanning
Zinc and penicillamine are lifelong medications for patients with Wilson
disease. Dosages vary with the severity of the disorder.
Another chelating agent is trientine, which may be more easily tolerated
than penicillamine.[1] Patients who do not respond to zinc therapy and
who have increased activities of liver enzymes should be identified so
that chelating agents may be added to the therapeutic regimen.
Class Summary
Penicillamine forms soluble complexes with metals excreted in urine. It was the drug of choice
before newer regimens were available. Because of extensive toxicities, alternative agents are
used. It must be administered with pyridoxine 25 mg by mouth daily.
Trientine (Syprine)
Trientine is an effective oral chelator used to induce cupruresis. It is useful for patients who
cannot tolerate penicillamine. It is indicated in Wilson disease if the initial presentation is
hepatic. It should be administered with zinc
Zinc (Galzin)
Zinc is a cofactor for more than 70 types of enzymes. It is approved for patients initially
treated with a chelating agent. It should be used for maintenance after initial chelation
therapy. Zinc acetate is the drug of choice in presymptomatic, pregnant, pediatric populations,
and in some instance for maintenance in compliant patients who have undergone copper
chelation therapy
Generally, penicillamine is the first treatment used
In rare cases where none of the oral treatments are effective, especially in severe
neurological disease, dimercaprol (British anti-Lewisite) is occasionally necessary. This
treatment is injected intramuscularly (into a muscle) every few weeks and has
unpleasant side effects such as pain.[12]
People who are asymptomatic (for instance, those diagnosed through family screening or
only as a result of abnormal test results) are generally treated, as the copper
accumulation may cause long-term damage in the future. It is unclear whether these
people are best treated with penicillamine or zinc acetate
Transplantation
The major complications in patients with untreated Wilson disease are those
associated with acute liver failure, chronic hepatic dysfunction with either
portal hypertension or hepatocellular carcinoma, and the sometimes-
relentless course to cirrhosis, which is characterized by a progressive
lassitude, fatigue, anorexia, jaundice, spider angiomas, splenomegaly, and
ascites. Bleeding from varices, hepatic encephalopathy, hepatorenal
syndrome, and coagulation abnormalities occur as liver failure ensues.
Death occurs, generally at age 30 years, if emergent liver transplantation is
not performed.