chorea Flashcards
chorea ddx?
Vascular: CL basal ganglia infarction, AV malformation, hemorrhage
Infectious: Viruses associated with chorea include measles, mumps, rubella, varicella-zoster, influenza, herpesvirus, Epstein-Barr virus, tick-borne encephalitis, West Nile encephalitis, cytomegalovirus, HIV
Toxic: phenytoin, valproic acid, neuroleptics espeacially first generation such as halidol, lithium, OCP, dopamine, metoclopramide, Carbon monoxide toxicity
Autoimmune: MS, PML, lupus, APLA, celiac, sydenhamn chorea
Metabolic: DM HbA1C mean 14 %, Nonketotic hyperglycemia , hyperthyrodism,
Inflammatory: neurosarcoid
Neoplasty: Anti Crmp5, Iglon 5, NMDA
Hereditary: HD, HDL2, wilson, SCA, DRPLA, chorea acanthocytosis, CJD, NBIA, Fahar
neuroleptics D2 receptor mechanism?
Dopamine binds to D1, stimulating the excitatory pathway, and to D2, inhibiting the inhibitory pathway thus increase motion.
when we block D2 receptors in mesolimbic pathway it reduces halucinations, blocking D2 receptors in nigrostriatal pathway will cause Extrapyramidal symptoms.
hemichorea ddx?
Hemichorea has been classically associated with focal vascular lesions of the contralateral subthalamic nucleus or basal ganglia. However, vascular lesions in other territories, such as the thalamus or temporoparietal cortex, have also been implicated in causing chorea.
Other etiologies that may cause hemichorea with focal lesions are nonketotic hyperglycemia and opportunistic infections in the setting of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS).
Some conditions may cause hemichorea in the absence of an apparent brain lesion. Examples include autoimmune chorea (eg, Sydenham chorea), paraneoplastic syndromes, and variant Creutzfeldt-Jakob disease.
However, these conditions may also present as generalized chorea.
OROBUCCOLINGUAL CHOREA ddx?
Orobuccolingual chorea may present in several conditions, with the most common being tardive syndromes.
Involvement of the orobuccolingual muscles may occur in paraneoplastic syndromes (eg, N-methyl-d-aspartate [NMDA] receptor encephalitis),
In chorea-acanthocytosis, chorea is frequently accompanied by oromandibular and lingual dystonia, leading to tongue protrusion and feeding dystonia.
Other etiologies of chorea may present with oromandibular dystonia. Some examples are Lesch-Nyhan syndrome, Lubag disease (X-linked dystonia-parkinsonism), Wilson disease, and pantothenate kinase–associated neurodegeneration (PKAN)
FACIAL OR FOREHEAD CHOREA ddx?
Chorea involving the forehead/upper face, manifested by frontalis contraction, intermittently widened palpebral fissures, and irregular blinking, is common in Huntington disease (HD). This is not a pathognomonic feature of HD but is far less common in tardive syndromes and can therefore help when seen in addition to delayed ocular saccade initiation and velocity or other features common in HD.
Genetic causes of chorea?
1.HD -autosomal dominant trinucleotide repeat expansion (CAG) in the huntingtin gene (HTT) on chromosome 4 Repeat lengths of 40 and above have full penetrance. symptoms progressive motor, cognitive, and neuropsychiatric behavioral changes. The average age of onset is in the third or fourth decade of life.
Juvenile HD (also known as the Westphal variant) occurs before the age of 20 and is associated with CAG repeat lengths higher than 55; it phenotypically can present with akinesia, parkinsonism, and seizures rather than chorea. Although chorea is the most common and prototypical movement disorder associated with HD, especially among those with onset in middle age or older adult life, other movements often seen include ataxia, dystonia, parkinsonism, tics, dysarthria, dysphagia, and impaired ocular saccade initiation and velocity.
- HDL2 is a rare autosomal dominant pathogenic variant in the gene encoding junctophilin-3 (JPH3). Like HD, it is associated with a CAG trinucleotide repeat expansion. It resembles HD and has primarily been reported in individuals of African descent. Acanthocye may be present
- DRPLA- inherited autosomal dominant - trinucleotide CAG expansion in the atrophin-1 gene (ATN1) on chromosome 12.
The clinical phenotype is similar to HD, chorea, ataxia, parkinsonism, epilepsy may also be seen. MRIs of individuals with DRPLA show characteristic white matter T2 hyperintensity changes and atrophy in regions indicated in the name of the disorder: the dentate, red nucleus, and pallidum.
4.. C9orf72- have increasingly been associated with various neurologic conditions, in particular motor neuron disease and frontotemporal dementia. In fact, the pathogenic variant is one of the most common genetic causes of amyotrophic lateral sclerosis and frontotemporal lobar degeneration in some populations. The expression can vary even among individuals in the same family. Although chorea is a rare manifestation of this pathogenic variant, it is now recognized among the most common phenocopies of HD, particularly among a UK-based cohort
- Neuroacanthocytosis refers to a group of extremely rare disorders with the characteristic feature of acanthocytes (spiculated, abnormally shaped red blood cells) found on peripheral blood smear. A. Chorea-acanthocytosis is a rare autosomal recessive cause of chorea movement in the orofacial and orobuccolingual regions is characteristically predominant. This can lead to self-injurious mutilation of the orobuccolingual region as well as prominent hypersalivation and dysphagia with lingual dystonia.
B. PKAN is an autosomal recessive disorder caused by a pathogenic variant in the pantothenate kinase 2 gene (PANK2) and can present from early childhood to midadulthood. It has a characteristic pattern of signal change in the basal ganglia on MRI known as the eye of the tiger sign. PKAN is also described as a neuroacanthocytosis syndrome.
C. X-linked McLeod syndrome and is associated with comorbid neuropathy and cardiomyopathy, chorea, seizures.
6.Wilson disease is an autosomal recessive genetic disorder in the gene encoding the ATP7B protein that transport of copper. ATP7B is highly expressed in hepatocytes, where it has dual roles in copper metabolism. First, ATP7B facilitates incorporation of copper into ceruloplasmin, which is then secreted into the bloodstream. Second, ATP7B promotes the biliary excretion of copper by sequestering copper into vesicles that are excreted into bile via exocytosis. Pathogenic variants in ATP7B lead to impaired copper excretion, resulting in copper accumulation in hepatocytes with resultant hepatotoxicity and accumulation of excess copper in other organs, including the brain. Neurologic symptoms can be the presenting manifestation in about 18% to 68% of patients. Anyone younger than 50 years of age with unexplained neurologic or hepatic findings should be considered for screening for Wilson disease using serum ceruloplasmin, 24-hour urine copper, and slit-lamp eye examination for Kayser-Fleisher rings. Neurologic symptoms are broad, but common manifestations include dysarthria, dystonia, tremor, ataxia, chorea, and parkinsonism. MRI of the brain in patients with Wilson disease commonly reveals changes within the bilateral basal ganglia as well as the thalami and brainstem on T1- or T2-weighted sequences. Hyperintense T2 signal in the midbrain surrounding the red nuclei in this condition has been dubbed the face of the giant panda sign.
HEREDITARY DISORDERS ASSOCIATED WITH BASAL GANGLIA MINERALIZATION
Hereditary forms of chorea can result from abnormal mineral accumulation in the basal ganglia.
This includes:
1. Iron (neurodegeneration with brain iron accumulation [NBIA] disorders)
2. Calcium (Fahr disease)
3. copper (Wilson disease), each of which may have corresponding MRI abnormalities.
PAROXYSMAL KINESIGENIC AND NONKINESIGENIC DYSKINESIA
Paroxysmal kinesigenic dyskinesia and paroxysmal nonkinesigenic dyskinesia are hereditary paroxysmal movement disorders that occur in childhood and are most commonly associated with chorea or dystonia. individuals typically have a normal neurologic examination between episodes, and the disorders can often be confused with functional movement disorders.
In paroxysmal kinesigenic dyskinesia (also known as DYT10), episodes typically last seconds to minutes and can occur countless times per day. Episodes are triggered by movement, but individuals will often describe a prodromal sensation before an episode. The choreiform movements can affect any body region but are often asymmetric, and they typically respond well to carbamazepine.
Paroxysmal kinesigenic dyskinesia is associated with autosomal dominant pathogenic variants in the proline-rich transmembrane protein 2 gene (PRRT2); the same gene has been associated with other conditions such as hemiplegic migraine and episodic ataxia.
In paroxysmal nonkinesigenic dyskinesia (also known as DYT8), episodes are typically longer, lasting minutes to hours. Episodes are also less frequent than in paroxysmal kinesigenic dyskinesia and are not triggered by movement but rather by stress, extremes of temperature, alcohol, or excitement.
Paroxysmal nonkinesigenic dyskinesia is less responsive to pharmacotherapy than paroxysmal kinesigenic dyskinesia.
Treatment chorea?
- VMAT2 inhibitors deplete the release of dopamine presynaptically by preventing packaging of monoamines into presynaptic storage vesicles.
This results in fewer movements as less dopamine is released from presynaptic terminals in the nigrostriatal pathway.
tetrabenazine and deutetrabenazine.
2.Neuroleptics D2-receptor blockade occurs with both typical and atypical neuroleptics and results in inhibition of the indirect pathway, thereby reducing movements. Despite having less disease-specific evidence for their use in chorea, neuroleptics are often used as adjunctive treatments for behavioral and psychiatric issues in HD and other degenerative choreas. They are sometimes also considered off-label for effects on weight gain and sleep. Neuroleptics with greater D2 blockade, such as typical neuroleptics, risperidone, and olanzapine, may be more effective in treating chorea than neuroleptics such as quetiapine and clozapine,
MRI hyperglycemia and chorea?
Hyperglycemia is a common metabolic cause of acute-onset chorea associated with T1 signal change in the contralateral putamen on MRI
