chorea curs complet .ppt

7/27/2019 CHOREA CURS COMPLET .ppt

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Chorea


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Chorea" is a borrowed Latin word that derives from theGreekkhoreia, a choral dance. The basic Greek word for

dance (written with the Roman alphabet) is khoros.

The ad hoc Committee on Classification of the WorldFederation of Neurologyhas defined chorea as

"a state of excessive, spontaneous movements,irregularly timed, non-repetitive, randomly distributedand abrupt in character. These movements may vary inseverity from restlessness with mild intermittentexaggeration of gesture and expression, fidgeting

movements of the hands, unstable dance-like gait to acontinuous flow of disabling, violent movements


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Patients with chorea exhibit motor impersistence (ie, they cannotmaintain a sustained posture).

When attempting to grip an object, they alternately squeezeand release ("milkmaid's grip"). When they attempt to protrude thetongue, the tongue often pops in and out ("harlequin's tongue").Patients often drop objects involuntarily. Also common are attemptsby patients to mask the chorea by voluntarily augmenting thechoreiform movements with semipurposeful movements.

Chorea involves both proximal and 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 isthe most common movement disorder, followed by Huntingtondisease
http://emedicine.medscape.com/article/1150165-overviewhttp://emedicine.medscape.com/article/1150165-overviewhttp://emedicine.medscape.com/article/1150165-overviewhttp://emedicine.medscape.com/article/1150165-overviewhttp://emedicine.medscape.com/article/1150165-overviewhttp://emedicine.medscape.com/article/1150165-overview


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The term athetosis comes from the Greek word athetos(notfixed).It is a slow form of chorea. Because of the slowness, themovements have a writhing (ie, squirming, twisting, or snakelike)appearance. Choreoathetosis is essentially an intermediate form.

Ballism or ballismus is considered a very severe form of chorea inwhich the movements have a violent, flinging quality.

In Greek, ballismosmeans "a jumping about or dancing."[2]Ballism has been defined as "continuous, violent, coordinated

involuntary activity involving the axial and proximal appendicularmusculature such that the limbs are flung about."

This movement disorder most often involves only one side ofthe body (ie, hemiballism or hemiballismus). Occasionally, bilateralmovements occur (ie, biballism or paraballism). Many patients withhemiballism have choreiform movements and vice versa, andhemiballism often evolves into hemichorea.


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Schematic diagram of the basal ganglia circuitry. Represented are the following: inhibitory (red arrows) and excitatory (green arrows)projections between the motor cortex, the putamen, the globus pallidus pars externa (GPe) and globus pallidus pars interna (GPi), thesubthalamic nucleus (STN), the substantia nigra pars reticulata (SNr) and substantia nigra pars compacta (SNc), and the ventrolateralthalamus (VL). D1 and D2 indicate the direct (regulated by dopamine D1 receptors) and indirect (regulated by dopamine D2 receptors)

pathways, respectively


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Pathophysiology

A simple model of basal ganglia function states that dopaminergicand GABAergic impulses from the substantia nigra and motorcortex, respectively, are funneled through the pallidum into themotor thalamus and motor cortex. These impulses are modulated inthe striatumvia two segregated, parallel, direct and indirect loops

through the medial pallidum and lateral pallidum/subthalamicnucleus. Subthalamic nucleus activity drives the medial pallidum toinhibit cortex-mediated impulses, thereby inducing parkinsonism.

Absent subthalamic nucleus inhibition enhances motor activity

through the motor thalamus, resulting in abnormal involuntarymovements such as dystonia, chorea, and tics. A classic example ofloss of subthalamic inhibitory drive is ballism


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History

Patients with chorea

may not initially be aware of the abnormal movements because they

may be subtle.can suppress the chorea temporarily and frequently camouflagesome of the movements by incorporating them into semipurposefulactivities (ie, parakinesia).

The inability to maintain voluntary contraction (ie, motorimpersistence), as is seen during manual grip (milkmaid grip) tests

or tongue protrusion, is a characteristic feature of chorea andresults in the dropping of 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 motorsymptoms include- dysarthria, dysphagia, postural instability, ataxia,dystonia, and myoclonus.


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Laboratory Studies Diagnosis of the primary choreatic conditions

history and clinical findings;

several laboratory studies are useful, especially in distinguishing the secondary forms of chorea from theprimary forms.

Huntington disease: The only laboratory study presently available to confirm HD is genetictesting. It identifies a gene abnormality in the short arm ofchromosome 4, characterizedby abnormal repetition of the trinucleotide CAG, the length of which determines the age ofonset (anticipation).

Wilson disease:A low serum ceruloplasmin level and serum copper values showingincreased urinary copper excretion corroborate the diagnosis in most cases.

Liver function test results are usually abnormal.If the diagnosis is still uncertain, liver biopsy can help confirm the diagnosis.

Sydenham chorea : The chorea can lag behind the etiologic streptococcal infection by 1-6months, sometimes as long as 30 years; therefore, antistreptococcal antibody titers mayno longer be elevated at presentation. Without documentation of an antecedentstreptococcal infection, the diagnosis of Sydenham chorea must be made by excludingother causes.

Neuroacanthocytosis: The diagnosis is confirmed by the presence of spiky erythrocytes(acanthocytes) in peripheral blood smears. The serum creatine kinase level may beelevated.

is based on


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Other laboratory studies useful in the differential diagnosis

of chorea include complement levels, antinuclear antibody titers,antiphospholipid antibody titers, amino acid levels in serum andurine, enzymatic studies from skin fibroblasts, thyrotropin levels,thyroxine values, and parathormone levels.


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Medical Care

Only symptomatic treatment is available for patients with

chorea.Chorea may be a disabling symptom, leading to bruises,fractures, and falls, and may impair the ability of patients to feedthemselves.

The most widely used agents in the treatment of chorea are theneuroleptics. 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 neurolepticsinclude haloperidol and fluphenazine.

Atypical neurolepticsinclude risperidone, olanzapine, clozapine, andquetiapine.

Dopamine-depleting agents, such as reserpine and

tetrabenazine, represent another option in the treatment of chorea. GABAergic drugs, such as clonazepam, gabapentin, and valproate, can be used as adjunctive therapy.


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Coenzyme Q10 alone and in combination with minocycline have

been proposed as potential therapies

Intravenous immunoglobulin and plasmapheresis may shorten thecourse of the illness and decrease symptom severity in patients with

Sydenham chorea.


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Surgical Care

Deep brain stimulation is an emerging technique thatmay benefit patients, at least in certain cases.

Although deep brain stimulation is not yet used routinely

for chorea, as it is for PD, exciting progress has beenmade with this modality.

Cell transplantation is controversial and in early stages ofresearch. It has shown variable results for HD patientparticipants.


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Causes of Chorea

Inherited

Ataxia-telangiectasia Benign hereditary chorea Hallervorden-Spatz disease Hereditary spinocerebellar ataxias Huntington disease Inborn errors of metabolism

Glutaric acidemia, Propionic acidemia ,Homocystinuria Phenylketonuria,Sulfite oxidasedeficiency

Mitochondrial encephalomyopathies Neuroacanthocvtosis Paroxysmal disorders

Paroxysmal kinesiogenic choreoathetosis

Paroxysmal nonkinesiogenic choreoathetosis

Pyruvate carboxylase deficiency Wilson disease


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Drugs Antimetabolites

Anticholinergics

Anticonvulsants (eg, phenytoin, carbamazepine, phenobarbital) Antidopaminergic agents (eg, phenothiazines, haloperidol, metoclopramide) Antihistamines CNS stimulants (eg, amphetamines, methylphenidate, pemoline) Lithium

Dopamine agonists (eg, levodopa) Oral contraceptives

Endocrine

Hyperthyroidism

Chorea gravidarum Hypoparathyroidism, pseudohypoparathyroidism
http://emedicine.medscape.com/article/121865-overviewhttp://emedicine.medscape.com/article/1149725-overviewhttp://emedicine.medscape.com/article/1149725-overviewhttp://emedicine.medscape.com/article/121865-overview


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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

Vasculopathies/vasculitis: Churg-Strauss syndrome[1] ,moyamoya
http://emedicine.medscape.com/article/329099-overviewhttp://emedicine.medscape.com/article/1146456-overviewhttp://emedicine.medscape.com/article/896540-overviewhttp://emedicine.medscape.com/article/1165183-overviewhttp://emedicine.medscape.com/article/330178-overviewhttp://emedicine.medscape.com/article/330178-overviewhttp://emedicine.medscape.com/article/1165183-overviewhttp://emedicine.medscape.com/article/896540-overviewhttp://emedicine.medscape.com/article/1146456-overviewhttp://emedicine.medscape.com/article/329099-overview


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Metabolic Hypocalcemia

Hypoglycemia and hyperglycemia Hypomagnesemia Hyponatremia, hypernatremia, and central pontine myelinolysis Renal failureMiscellaneous Cerebral palsy

Head trauma Bronchopulmonary dysplasia (infantile chorea) Cardiopulmonary bypass - "Postpump chorea

Neoplastic Primary and metastatic brain tumors Primary CNS lymphomaToxinsCO, Mg, organophosphate


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Rheumatic (Sydenham) Chorea

In 1684, Thomas Sydenham described the clinical syndrome thatnow bears his name. Originally termed St. Vitus' dance, it now isreferred to as rheumatic chorea. Stoll first proposed a relationshipbetween Sydenham chorea and rheumatic fever (RF) in 1780.

In 1889, Cheadle described the full rheumatic syndrome ofcarditis,

polyarthritis, chorea, subcutaneous nodules, and erythemamarginatum. 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 andanxiety.


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Epidemiology

Sydenham chorea is the most common cause of acquired chorea in theyoung. During the latter part of the twentieth century the number ofreported cases of RF in the United States increased. This resurgenceappears to be associated with strains of group A beta hemolyticstreptococcal 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.

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 presentbetween 5-15 years of age.


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In about 20% of patients, only one side of the body may

seem to be affected (hemichorea); however, carefulexamination usually reveals some involvement of the oppositeside.

The choreic movements interfere with volitional movementsand result in a clumsy gait, dropping and spilling, andexplosive bursts of dysarthric speech.

Muscular weakness leads to inability to sustain a contraction(milkmaid's grip).

The pronator sign consists of hyperpronation of the hands,causing the palms to face outward when the arms are held overthe 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.


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Some children may have such profound weakness that theyappear paralyzed. Not uncommonly, children are restricted tobed or are unable to attend school for the duration of theillness. Fortunately, paralytic chorea is uncommon.

Patients with SC may also have psychiatric symptoms such asdepression, anxiety, personality changes, emotional lability,OCD, and attention deficit disorder (ADD).

Occasionally, these symptoms precede the onset of chorea


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On average, the disease resolves spontaneously in 3-6 months andrarely 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 2years after the initial attack.


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Pathophysiology

Immunology: Evidence suggests that SC may result from the production ofimmunoglobin G antibodies that crossreact with antigens in the membrane of group Astreptococci and antigens in the neuronal cytoplasm of the caudate and subthalamic

nuclei, namely intracellular tubulinand extracellular lysoganglioside.Antineuronal antibodies have also been found in the cerebrospinal fluid (CSF) ofpatients with acute rheumatic chorea. Immunofluorescent staining has shown thatsera from approximately half of the children with SC have antibodies that react withneuronal cytoplasmic antigens in the caudate and subthalamic nuclei.

Serum antineuronal antibody titers have been found to decrease as the choreaimproves.

In children who suffer a relapse, the increase in symptom severity correlates with arise in these neuronal antibodies.


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Neuroimaging

MRI findings in SC are not consistent and may benormal.

Functional neuroimaging using fluorodeoxyglucose (FDG)positron emission tomography (PET) has demonstrated

reversible striatal hypermetaboli.


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Treatment

Treatment and prevention may involve multiple fields of discipline,including infectious diseases, cardiology, and neurology. For thisreason, several different classes of medications are used. These

include antibiotic, neuroleptic, and cardiac medications

(ethiologyc, pathogenic, symptomatic) A.The primary goal of treating an ARF attack is to eradicate streptococcalorganisms and bacterial antigens from the pharyngeal region.

Penicillin is the drug of choice in persons who are not at risk ofallergic reaction. A single parenteral injection of benzathine benzylpenicillincan ensure compliance.

Oral cephalosporins, rather than erythromycin, are recommended as

an alternative in patients who are allergic to penicillin. However, be

cautious of the 20% cross-reactivity of the cephalosporins with penicillin


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B. Steroidshave been used widely, but no controlled studies have been done


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y,to confirm steroid efficacy in chorea.Patients with carditis require prednisone. The goal is to decrease myocardialinflammation. May decrease inflammation by reversing increased capillarypermeability and suppressing PMN activity. After 2-3 wk, dosage may tapered,

reduced 25% each week. . Prednisone,

plasma exchange and intravenous immunoglobulin (IVIG) have beenshown to be effective. Case reports have suggested IVIG to be a safe,

effective option in disabling SC. Immunologic treatment can also be effective but is expensive and may be

associated with significant side effects.

The presence of antineuronal antibodies suggests that intravenousimmunoglobulin (IVIg) and plasma exchange may be effective.

More recent reports have shown IVIG to be an effective safe option.Because this treatment modality is quite expensive, it should be reservedfor protracted or debilitating cases.
http://reference.medscape.com/drug/prednisone-intensol-342747http://reference.medscape.com/drug/gammagard-s-d-carimune-nf-immune-globulin-iv-igiv-343138http://reference.medscape.com/drug/gammagard-s-d-carimune-nf-immune-globulin-iv-igiv-343138http://reference.medscape.com/drug/prednisone-intensol-342747


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Chorea gravidarum

Background

Chorea gravidarum (CG) is the term given to chorea occurringduring pregnancy. This is not an etiologically or pathologicallydistinct morbid entity but a generic term for chorea of anycause starting during pregnancy.

Chorea gravidarum is regarded as a syndrome rather than aspecific disease entity.


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Patientprofile

Most patients with chorea gravidarum are young; theaverage age is 22 years.

Of initial attacks, 80% occur during first pregnancies,

and one half start during the first trimester.One thirdbegin in the second trimester.

Of afflicted women, 60% previously had chorea.Recurrences may occur in subsequent pregnancies,

particularly if antiphospholipid syndrome is the cause.


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Pathophysiology

The most striking neuropathology in HD occurs withinthe neostriatum, in which gross atrophy of the caudatenucleus and putamenis accompanied by selectiveneuronal loss and astrogliosis.

Marked neuronal loss also is seen in deep layers of the

cerebral cortex. Other regions, including the globuspallidus, thalamus, subthalamic nucleus, substantianigra, and cerebellum, show varying degrees of atrophydepending on the pathologic grade.

The extent of gross striatal pathology, neuronal loss, andgliosis provides a basis for grading the severity of HDpathology (grades 0-4)


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h b f


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is the expansion of a cysteine-adenosine-guanine (CAG) repeatencoding a polyglutamine tract in the N-terminus of the proteinproduct called huntingtin.

The function of huntingtin is not known. Normally, it is located inthe cytoplasm. The association of huntingtin with the cytoplasmicsurface of a variety of organelles, including transport vesicles,synaptic vesicles, microtubules, and mitochondria, raises thepossibility of the occurrence of normal cellular interactions that

might be relevant to neurodegeneration.

N-terminal fragments of mutant huntingtin accumulate and forminclusionsin the cell nucleus in the brains of patients with HD, aswell as in various animal and cell models of HD.

The presence of neuronal intranuclear inclusions (NIIs)initially ledto the view that they are toxic and, hence, pathogenic

The genetic basis of HD

E id i l


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Epidemiology

Frequency

United States

Estimates of the prevalence of HD in the United Statesrange from 4.1-8.4 per 100,000 people. Accurateestimates of the incidence of HD are not available.

International

The prevalence in most European countries ranges from1.63-9.95 per 100,000 people. The prevalence of HD inFinland and Japan is less than 1 per 100,000 people.


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Huntington Disease Clinical Presentation

The clinical features of Huntington disease (HD) include amovement disorder, a cognitive disorder, and a behavioraldisorder. Patients may present with one or all disorders invarying degrees.

Chorea (derived from the Greek word meaning to dance) is

the most common movement disorder seen in HD.
http://emedicine.medscape.com/article/1149854-overviewhttp://emedicine.medscape.com/article/1149854-overview


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Imaging Studies

No single imaging technique is necessary or sufficient fordiagnosis of Huntington disease (HD).

Measurement of the bicaudate diameter (ie, the distancebetween the heads of the 2 caudate nuclei) by CT scanor MRI is a reliable marker of HD.


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Medical Care

Depression in patients with HD is treatable and should be recognizedpromptly. Selective serotonin reuptake inhibitors (SSRIs) should beconsidered as first-line therapy. Other antidepressants, including bupropion,venlafaxine, nefazodone, and tricyclic antidepressants, also can be used.Electroconvulsive therapy (ECT) can be used in patients with refractorydepression.

Antipsychotic medications may be necessary in patients with hallucinations,delusions, or schizophrenia-like syndromes. Newer agents, such asquetiapine, clozapine, olanzapine, and risperidone, are preferred to olderagents because of the lower incidence of extrapyramidal side effects and thedecreased risk for tardive syndromes.

Irritability may be treated with antidepressants, particularly the SSRIs;mood stabilizers, such as valproic acid or carbamazepine; and, if needed,atypical neuroleptics.

Other less frequent aspects of HD that may require pharmacologictreatment are mania, obsessive-compulsive disorder, anxiety, sexual

disorders, myoclonus, tics, dystonia, and epilepsy.


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Patients with Wilson disease more often initially present withhepatic manifestations when identified in the first decade of

life as compared with more neuropsychiatric illness later,and the latter most commonly occurs during the thirddecade.

The diagnosis is established by no individual test but requires

the use of some combination of serum ceruloplasmin level,urinary copper excretion, presence of Kayser-Fleischer rings,and hepatic copper content when biopsy is required.


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Excess copper may be rendered nontoxic by forming complexes with apo-


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Excess copper may be rendered nontoxic by forming complexes with apo-metallothionein to produce copper-metallothionein, or it may be excreted intobile. Normal copper balance is maintained by regulation of excretion, rather thanabsorption, and the predominant route of copper excretion (approximately 95%)is hepatobiliary in nature.

In Wilson disease, the processes of incorporation of copper intoceruloplasmin and excretion of excess copper into bile are impaired. Thetransport of copper by the copper-transporting P-type ATPase is defective inWilson disease secondary to one of several mutations in theATP7Bgene. Bygenetic linkage studies, Bowcock and colleagues narrowed the assignment of the

Wilson disease locus to 13q14-q21.


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Neuropsychiatric features


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Neuropsychiatric features

Most patientswho present with neuropsychiatric manifestations have cirrhosis.

The most common presentingneurologic featureis asymmetric tremor, which isvariable in character and may be predominantly resting, postural, or kinetic.

Frequent early symptoms include the following: Difficulty speaking Excessive salivation Ataxia

Masklike facies Clumsiness with the hands Personality changesLate manifestations (now rare because of earlier diagnosis and treatment) include the

following: Dystonia Spasticity

Grand mal seizures Rigidity Flexion contractures


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Ophthalmic findings

Sunflower cataractsare brilliantly multicolored and are visible only onslit-lamp examination.

They do not impair vision.

Other relatively uncommon ophthalmic findings include exotropicstrabismus, optic neuritis or pallor of the optic disc


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DIAGNOSIS


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G OS S

Approach Considerations

The presence ofKayser-Fleischer rings and ceruloplasmin levelsof less than 20 mg/dL in a patient with neurologic signs orsymptoms suggest a diagnosis of Wilson disease.

If a patient is asymptomatic, exhibits isolated liver disease, andlacks corneal rings, the coexistence of a hepatic copperconcentration of more than 250 mg/g of dry weight and a lowserum ceruloplasmin level is sufficient to establish a diagnosis.Therefore, in the absence of Kayser-Fleischer rings orneurologic abnormalities, a liver biopsy for quantitative copper

determination is essential to establish the diagnosis of Wilsondisease.


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With clinical progression, acute liver failure, or worseninghepatic function, the patient must be evaluated at a centerwith expertise in Wilson disease and the capability to performliver transplantation.

Orthotopic liver transplantation is curative treatment forWilson disease.


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Prognosis

Important clues for the diagnosis of Wilson disease that aclinician must recognize are a younger patient withhemolytic anemia, impaired hepatic synthetic function, andnormal alkaline phosphatase values.


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chorea curs complet .ppt

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