The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
M W Cunningham - One of the best experts on this subject based on the ideXlab platform.
-
Tubulin Is a Neuronal Target of Autoantibodies in Sydenham's Chorea
The Journal of Immunology, 2014Co-Authors: C. A. Kirvan, C. J. Cox, S. E. Swedo, M W CunninghamAbstract:Sydenham's Chorea is a CNS disorder and sequela of group A streptococcal infection where deposition of Abs in brain may result in movement and neuropsychiatric abnormalities. We studied human mAbs 24.3.1, 31.1.1, and 37.2.1 derived from Chorea and selected for cross-reactivity with group A streptococci and brain Ags. Our novel findings reveal that Sydenham's Chorea mAbs target a 55-kDa brain protein with an N-terminal amino acid sequence of MREIVHLQ corresponding to beta-tubulin. Chorea mAb specificity for purified brain tubulin was confirmed in ELISA and Western immunoblot, and significant levels of anti-tubulin IgG were found in acute Chorea sera and cerebrospinal fluid. Lysoganglioside G(M1) inhibited binding of Chorea mAbs to tubulin and mAb reactivity with human caudate and putamen brain sections was blocked by anti-tubulin mAb. The Chorea mAbs labeled both intra- and extracellular Ags of a neuronal cell line providing evidence suggesting mimicry between intracellular brain protein tubulin and extracellular lysoganglioside. In addition, Chorea mAb 24.3.1 and acute Chorea sera induced calcium/calmodulin-dependent protein kinase II activity in human neuronal cells. Nucleotide sequence analysis of the Chorea mAb V(H) genes revealed that mAb 24.3.1 V(H) gene was encoded by the V(H)1 germline gene family which encodes other anti-ganglioside V(H) genes associated with motor neuropathies. mAb recognition of tubulin and the neuronal cell surface with initiation of cell signaling and dopamine release supports an emerging theme in autoimmunity whereby cross-reactive or polyreactive autoantibodies against intracellular Ags recognize cell surface epitopes potentially leading to disease.
-
tubulin is a neuronal target of autoantibodies in sydenham s Chorea
Journal of Immunology, 2007Co-Authors: C. A. Kirvan, S. E. Swedo, M W CunninghamAbstract:Sydenham’s Chorea is a CNS disorder and sequela of group A streptococcal infection where deposition of Abs in brain may result in movement and neuropsychiatric abnormalities. We studied human mAbs 24.3.1, 31.1.1, and 37.2.1 derived from Chorea and selected for cross-reactivity with group A streptococci and brain Ags. Our novel findings reveal that Sydenham’s Chorea mAbs target a 55-kDa brain protein with an N-terminal amino acid sequence of MREIVHLQ corresponding to β-tubulin. Chorea mAb specificity for purified brain tubulin was confirmed in ELISA and Western immunoblot, and significant levels of anti-tubulin IgG were found in acute Chorea sera and cerebrospinal fluid. Lysoganglioside G M1 inhibited binding of Chorea mAbs to tubulin and mAb reactivity with human caudate and putamen brain sections was blocked by anti-tubulin mAb. The Chorea mAbs labeled both intra- and extracellular Ags of a neuronal cell line providing evidence suggesting mimicry between intracellular brain protein tubulin and extracellular lysoganglioside. In addition, Chorea mAb 24.3.1 and acute Chorea sera induced calcium/calmodulin-dependent protein kinase II activity in human neuronal cells. Nucleotide sequence analysis of the Chorea mAb V H genes revealed that mAb 24.3.1 V H gene was encoded by the V H 1 germline gene family which encodes other anti-ganglioside V H genes associated with motor neuropathies. mAb recognition of tubulin and the neuronal cell surface with initiation of cell signaling and dopamine release supports an emerging theme in autoimmunity whereby cross-reactive or polyreactive autoantibodies against intracellular Ags recognize cell surface epitopes potentially leading to disease.
-
streptococcal mimicry and antibody mediated cell signaling in the pathogenesis of sydenham s Chorea
Autoimmunity, 2006Co-Authors: C. A. Kirvan, S. E. Swedo, David Kurahara, M W CunninghamAbstract:Recent evidence suggests that the pathogenesis of Sydenham's Chorea following group A streptococcal infection is due to antibodies which develop due to the infection and infiltrate the brain and basal ganglia. Antibodies present in acute Chorea react with the surface of neuronal cells and signal the induction of calcium calmodulin dependent protein kinase II with elevation of tyrosine hydroxylase and subsequent dopamine release which may lead to the movement disorder. The antibodies present in disease recognize lysoganglioside and the group A streptococcal epitope, N-acetyl-glucosamine. Monoclonal antibodies (mAbs) from Sydenham's Chorea demonstrated the mimicry between lysoganglioside and the group A streptococcal carbohydrate epitope. A group of antibodies present in pediatric autoimmune neuropsychiatric disorders (PANDAS) were similar but not identical to the antibodies observed in Chorea.
-
mimicry and autoantibody mediated neuronal cell signaling in sydenham Chorea
Nature Medicine, 2003Co-Authors: C. A. Kirvan, S. E. Swedo, Janet S Heuser, M W CunninghamAbstract:Streptococcus pyogenes–induced acute rheumatic fever (ARF) is one of the best examples of postinfectious autoimmunity due to molecular mimicry between host and pathogen. Sydenham Chorea is the major neurological manifestation of ARF but its pathogenesis has remained elusive, with no candidate autoantigen or mechanism of pathogenesis described. Chorea monoclonal antibodies showed specificity for mammalian lysoganglioside and N-acetyl-β-D-glucosamine (GlcNAc), the dominant epitope of the group A streptococcal (GAS) carbohydrate. Chorea antibodies targeted the surface of human neuronal cells, with specific induction of calcium/calmodulin-dependent protein (CaM) kinase II activity by monoclonal antibody 24.3.1 and sera from active Chorea. Convalescent sera and sera from other streptococcal diseases in the absence of Chorea did not activate the kinase. The new evidence implicates antibody-mediated neuronal cell signaling in the immunopathogenesis of Sydenham Chorea and will lead to a better understanding of other antibody-mediated neurological disorders.
C. A. Kirvan - One of the best experts on this subject based on the ideXlab platform.
-
Tubulin Is a Neuronal Target of Autoantibodies in Sydenham's Chorea
The Journal of Immunology, 2014Co-Authors: C. A. Kirvan, C. J. Cox, S. E. Swedo, M W CunninghamAbstract:Sydenham's Chorea is a CNS disorder and sequela of group A streptococcal infection where deposition of Abs in brain may result in movement and neuropsychiatric abnormalities. We studied human mAbs 24.3.1, 31.1.1, and 37.2.1 derived from Chorea and selected for cross-reactivity with group A streptococci and brain Ags. Our novel findings reveal that Sydenham's Chorea mAbs target a 55-kDa brain protein with an N-terminal amino acid sequence of MREIVHLQ corresponding to beta-tubulin. Chorea mAb specificity for purified brain tubulin was confirmed in ELISA and Western immunoblot, and significant levels of anti-tubulin IgG were found in acute Chorea sera and cerebrospinal fluid. Lysoganglioside G(M1) inhibited binding of Chorea mAbs to tubulin and mAb reactivity with human caudate and putamen brain sections was blocked by anti-tubulin mAb. The Chorea mAbs labeled both intra- and extracellular Ags of a neuronal cell line providing evidence suggesting mimicry between intracellular brain protein tubulin and extracellular lysoganglioside. In addition, Chorea mAb 24.3.1 and acute Chorea sera induced calcium/calmodulin-dependent protein kinase II activity in human neuronal cells. Nucleotide sequence analysis of the Chorea mAb V(H) genes revealed that mAb 24.3.1 V(H) gene was encoded by the V(H)1 germline gene family which encodes other anti-ganglioside V(H) genes associated with motor neuropathies. mAb recognition of tubulin and the neuronal cell surface with initiation of cell signaling and dopamine release supports an emerging theme in autoimmunity whereby cross-reactive or polyreactive autoantibodies against intracellular Ags recognize cell surface epitopes potentially leading to disease.
-
tubulin is a neuronal target of autoantibodies in sydenham s Chorea
Journal of Immunology, 2007Co-Authors: C. A. Kirvan, S. E. Swedo, M W CunninghamAbstract:Sydenham’s Chorea is a CNS disorder and sequela of group A streptococcal infection where deposition of Abs in brain may result in movement and neuropsychiatric abnormalities. We studied human mAbs 24.3.1, 31.1.1, and 37.2.1 derived from Chorea and selected for cross-reactivity with group A streptococci and brain Ags. Our novel findings reveal that Sydenham’s Chorea mAbs target a 55-kDa brain protein with an N-terminal amino acid sequence of MREIVHLQ corresponding to β-tubulin. Chorea mAb specificity for purified brain tubulin was confirmed in ELISA and Western immunoblot, and significant levels of anti-tubulin IgG were found in acute Chorea sera and cerebrospinal fluid. Lysoganglioside G M1 inhibited binding of Chorea mAbs to tubulin and mAb reactivity with human caudate and putamen brain sections was blocked by anti-tubulin mAb. The Chorea mAbs labeled both intra- and extracellular Ags of a neuronal cell line providing evidence suggesting mimicry between intracellular brain protein tubulin and extracellular lysoganglioside. In addition, Chorea mAb 24.3.1 and acute Chorea sera induced calcium/calmodulin-dependent protein kinase II activity in human neuronal cells. Nucleotide sequence analysis of the Chorea mAb V H genes revealed that mAb 24.3.1 V H gene was encoded by the V H 1 germline gene family which encodes other anti-ganglioside V H genes associated with motor neuropathies. mAb recognition of tubulin and the neuronal cell surface with initiation of cell signaling and dopamine release supports an emerging theme in autoimmunity whereby cross-reactive or polyreactive autoantibodies against intracellular Ags recognize cell surface epitopes potentially leading to disease.
-
streptococcal mimicry and antibody mediated cell signaling in the pathogenesis of sydenham s Chorea
Autoimmunity, 2006Co-Authors: C. A. Kirvan, S. E. Swedo, David Kurahara, M W CunninghamAbstract:Recent evidence suggests that the pathogenesis of Sydenham's Chorea following group A streptococcal infection is due to antibodies which develop due to the infection and infiltrate the brain and basal ganglia. Antibodies present in acute Chorea react with the surface of neuronal cells and signal the induction of calcium calmodulin dependent protein kinase II with elevation of tyrosine hydroxylase and subsequent dopamine release which may lead to the movement disorder. The antibodies present in disease recognize lysoganglioside and the group A streptococcal epitope, N-acetyl-glucosamine. Monoclonal antibodies (mAbs) from Sydenham's Chorea demonstrated the mimicry between lysoganglioside and the group A streptococcal carbohydrate epitope. A group of antibodies present in pediatric autoimmune neuropsychiatric disorders (PANDAS) were similar but not identical to the antibodies observed in Chorea.
-
mimicry and autoantibody mediated neuronal cell signaling in sydenham Chorea
Nature Medicine, 2003Co-Authors: C. A. Kirvan, S. E. Swedo, Janet S Heuser, M W CunninghamAbstract:Streptococcus pyogenes–induced acute rheumatic fever (ARF) is one of the best examples of postinfectious autoimmunity due to molecular mimicry between host and pathogen. Sydenham Chorea is the major neurological manifestation of ARF but its pathogenesis has remained elusive, with no candidate autoantigen or mechanism of pathogenesis described. Chorea monoclonal antibodies showed specificity for mammalian lysoganglioside and N-acetyl-β-D-glucosamine (GlcNAc), the dominant epitope of the group A streptococcal (GAS) carbohydrate. Chorea antibodies targeted the surface of human neuronal cells, with specific induction of calcium/calmodulin-dependent protein (CaM) kinase II activity by monoclonal antibody 24.3.1 and sera from active Chorea. Convalescent sera and sera from other streptococcal diseases in the absence of Chorea did not activate the kinase. The new evidence implicates antibody-mediated neuronal cell signaling in the immunopathogenesis of Sydenham Chorea and will lead to a better understanding of other antibody-mediated neurological disorders.
Francisco Cardoso - One of the best experts on this subject based on the ideXlab platform.
-
Treatment of Sydenham’s Chorea
Current Clinical Neurology, 2019Co-Authors: Francisco CardosoAbstract:Sydenham’s Chorea, an autoimmune movement disorder caused by Streptococcus-induced antibodies that cross-react with basal ganglia antigens, is the most common cause of acute Chorea in children worldwide. The clinical features include Chorea and other motor findings as well as non-motor features such as obsessions, compulsions, and hyperactivity. The management is based on control of Chorea and prophylaxis of new streptococcal infections. Although there are no evidence-based recommendations, valproic acid and other anticonvulsant agents are the first-line antichoreic agents. Risperidone and other neuroleptics are used for patients who fail to improve with anticonvulsant agents. If patients do not respond to the first- and second-line agents, they should be treated with corticosteroids. Prophylaxis with antibiotics is warranted to prevent recurrence of rheumatic fever.
-
Chorea: A Journey through History.
Tremor and other hyperkinetic movements (New York N.Y.), 2015Co-Authors: Thiago Cardoso Vale, Francisco CardosoAbstract:The original descriptions of Chorea date from the Middle Ages, when an epidemic of “dancing mania” swept throughout Europe. The condition was initially considered a curse sent by a saint, but was named “Saint Vitus’s dance” because afflicted individuals were cured if they touched churches storing Saint Vitus’s relics. Paracelsus coined the term Chorea Sancti Viti and recognized different forms of Chorea (imaginativa, lasciva, and naturalis). In the 17th century, Thomas Sydenham provided an accurate description of what he termed Chorea minor. He also described rheumatic fever but did not associate it with Chorea. It was only in 1850 that See established a relationship between Chorea and rheumatic disease. A connection with cardiac involvement was soon recognized and in 1866 Roger postulated that Chorea, arthritis, and heart disease had a common cause. The last quarter of the 19th century is marked by the works of Jean‐Martin Charcot, Silas Weir Mitchell, William Osler, and William Richard Gowers, all of paramount importance in the refinement of the definition of Chorea, its causes, and differential diagnosis. In 1841, Charles Oscar Waters gave a concise account of a syndrome, likely to be Huntington’s disease (HD), later described further by George Huntington and named after him. In 1955, the Venezuelan physician Americo Negrette published a book describing communities in the State of Zulia in Venezuela, with unusual numbers of individuals with Chorea. Negrette’s works culminated in the creation of the Venezuela project and the subsequent discovery of seminal findings in HD. We review the historical facts and outstanding physicians that mark both HD and Sydenham’s Chorea’s history in various sections.
-
Pregnancy in patients with Sydenham's Chorea.
Parkinsonism & Related Disorders, 2012Co-Authors: Débora Palma Maia, Patricia G. Fonseca, Sarah Teixeira Camargos, Cláudia Pfannes, Mauro C. Cunningham, Francisco CardosoAbstract:Abstract Background Sydenham’s Chorea is a frequent cause of Chorea during pregnancy, Chorea gravidarum. The aim of this article is to describe the effect of pregnancy in a consecutive series of patients with diagnosis of Sydenham’s Chorea. Methods A chart review was performed of all patients with the diagnosis of Sydenham’s Chorea followed up at our institution from 07/1993 through 08/2010 and who became pregnant. Results From 66 patients, 20 became pregnant. Of these 20 patients, 15 (75%) developed Chorea gravidarum. Generalized Chorea was found in 67% of these 15 patients, focal or multifocal Chorea was identified in 20% and 13.4% developed hemiChorea. In 80% of cases Chorea began in the first 6 months of gestation. Three women with previous persistent Chorea experienced worsening of the movement disorder during pregnancy. Remission occurred after delivery in 11 patients whereas the other four remained with non-disabling Chorea during the first 12 months after delivery. Abortion occurred in two patients (13%). All patients with Chorea gravidarum subsequently treated with oral contraceptives developed recurrence of Chorea. Conclusions Chorea gravidarum is a frequent complication of pregnancy in patients with previous history of Sydenham’s Chorea and an increased risk of miscarriage should be considered. Our findings confirm the notion that Chorea gravidarum results from hormonal changes acting on previously dysfunctional basal ganglia.
-
Huntington Disease and Other Choreas
Neurologic Clinics, 2009Co-Authors: Francisco CardosoAbstract:: Chorea is defined as a syndrome characterized by brief, abrupt involuntary movements resulting from a continuous flow of random muscle contractions. There are genetic and non-genetic causes of Chorea. The most common genetic cause of Chorea is Huntington's disease (HD). Non-genetic forms of Chorea include vascular Choreas, auto-immune Choreas, metabolic and toxic Choreas, and drug-induced Choreas. This chapter provides an overview of clinical features, pathogenesis and management of HD, other important genetic causes of Chorea, Sydenham's Chorea, other autoimmune Choreas and vascular Choreas.
-
Seminar on Choreas
Lancet Neurology, 2006Co-Authors: Francisco Cardoso, Klaus Seppi, Katherina J. Mair, Gregor K. Wenning, Werner PoeweAbstract:Summary Chorea is one of the major types of involuntary movement disorders originating from dysfunctional neuronal networks interconnecting the basal ganglia and frontal cortical motor areas. The syndrome is characterised by a continuous flow of random, brief, involuntary muscle contractions and can result from a wide variety of causes. Diagnostic work-up can be straightforward in patients with a positive family history of Huntington's disease or acute-onset hemiChorea in patients with lacunar stroke, but it can be a challenging and complex task in rare autoimmune or genetic Choreas. Principles of management focus on establishing an aetiological classification and, if possible, removal of the cause. Preventive strategies may be possible in Huntington's disease where genetic counselling plays a major part. In this review we summarise the current understanding of the neuroanatomy and pathophysiology of Chorea, its major aetiological classes, and principles of diagnostic work-up and management.
S. E. Swedo - One of the best experts on this subject based on the ideXlab platform.
-
Tubulin Is a Neuronal Target of Autoantibodies in Sydenham's Chorea
The Journal of Immunology, 2014Co-Authors: C. A. Kirvan, C. J. Cox, S. E. Swedo, M W CunninghamAbstract:Sydenham's Chorea is a CNS disorder and sequela of group A streptococcal infection where deposition of Abs in brain may result in movement and neuropsychiatric abnormalities. We studied human mAbs 24.3.1, 31.1.1, and 37.2.1 derived from Chorea and selected for cross-reactivity with group A streptococci and brain Ags. Our novel findings reveal that Sydenham's Chorea mAbs target a 55-kDa brain protein with an N-terminal amino acid sequence of MREIVHLQ corresponding to beta-tubulin. Chorea mAb specificity for purified brain tubulin was confirmed in ELISA and Western immunoblot, and significant levels of anti-tubulin IgG were found in acute Chorea sera and cerebrospinal fluid. Lysoganglioside G(M1) inhibited binding of Chorea mAbs to tubulin and mAb reactivity with human caudate and putamen brain sections was blocked by anti-tubulin mAb. The Chorea mAbs labeled both intra- and extracellular Ags of a neuronal cell line providing evidence suggesting mimicry between intracellular brain protein tubulin and extracellular lysoganglioside. In addition, Chorea mAb 24.3.1 and acute Chorea sera induced calcium/calmodulin-dependent protein kinase II activity in human neuronal cells. Nucleotide sequence analysis of the Chorea mAb V(H) genes revealed that mAb 24.3.1 V(H) gene was encoded by the V(H)1 germline gene family which encodes other anti-ganglioside V(H) genes associated with motor neuropathies. mAb recognition of tubulin and the neuronal cell surface with initiation of cell signaling and dopamine release supports an emerging theme in autoimmunity whereby cross-reactive or polyreactive autoantibodies against intracellular Ags recognize cell surface epitopes potentially leading to disease.
-
tubulin is a neuronal target of autoantibodies in sydenham s Chorea
Journal of Immunology, 2007Co-Authors: C. A. Kirvan, S. E. Swedo, M W CunninghamAbstract:Sydenham’s Chorea is a CNS disorder and sequela of group A streptococcal infection where deposition of Abs in brain may result in movement and neuropsychiatric abnormalities. We studied human mAbs 24.3.1, 31.1.1, and 37.2.1 derived from Chorea and selected for cross-reactivity with group A streptococci and brain Ags. Our novel findings reveal that Sydenham’s Chorea mAbs target a 55-kDa brain protein with an N-terminal amino acid sequence of MREIVHLQ corresponding to β-tubulin. Chorea mAb specificity for purified brain tubulin was confirmed in ELISA and Western immunoblot, and significant levels of anti-tubulin IgG were found in acute Chorea sera and cerebrospinal fluid. Lysoganglioside G M1 inhibited binding of Chorea mAbs to tubulin and mAb reactivity with human caudate and putamen brain sections was blocked by anti-tubulin mAb. The Chorea mAbs labeled both intra- and extracellular Ags of a neuronal cell line providing evidence suggesting mimicry between intracellular brain protein tubulin and extracellular lysoganglioside. In addition, Chorea mAb 24.3.1 and acute Chorea sera induced calcium/calmodulin-dependent protein kinase II activity in human neuronal cells. Nucleotide sequence analysis of the Chorea mAb V H genes revealed that mAb 24.3.1 V H gene was encoded by the V H 1 germline gene family which encodes other anti-ganglioside V H genes associated with motor neuropathies. mAb recognition of tubulin and the neuronal cell surface with initiation of cell signaling and dopamine release supports an emerging theme in autoimmunity whereby cross-reactive or polyreactive autoantibodies against intracellular Ags recognize cell surface epitopes potentially leading to disease.
-
streptococcal mimicry and antibody mediated cell signaling in the pathogenesis of sydenham s Chorea
Autoimmunity, 2006Co-Authors: C. A. Kirvan, S. E. Swedo, David Kurahara, M W CunninghamAbstract:Recent evidence suggests that the pathogenesis of Sydenham's Chorea following group A streptococcal infection is due to antibodies which develop due to the infection and infiltrate the brain and basal ganglia. Antibodies present in acute Chorea react with the surface of neuronal cells and signal the induction of calcium calmodulin dependent protein kinase II with elevation of tyrosine hydroxylase and subsequent dopamine release which may lead to the movement disorder. The antibodies present in disease recognize lysoganglioside and the group A streptococcal epitope, N-acetyl-glucosamine. Monoclonal antibodies (mAbs) from Sydenham's Chorea demonstrated the mimicry between lysoganglioside and the group A streptococcal carbohydrate epitope. A group of antibodies present in pediatric autoimmune neuropsychiatric disorders (PANDAS) were similar but not identical to the antibodies observed in Chorea.
-
mimicry and autoantibody mediated neuronal cell signaling in sydenham Chorea
Nature Medicine, 2003Co-Authors: C. A. Kirvan, S. E. Swedo, Janet S Heuser, M W CunninghamAbstract:Streptococcus pyogenes–induced acute rheumatic fever (ARF) is one of the best examples of postinfectious autoimmunity due to molecular mimicry between host and pathogen. Sydenham Chorea is the major neurological manifestation of ARF but its pathogenesis has remained elusive, with no candidate autoantigen or mechanism of pathogenesis described. Chorea monoclonal antibodies showed specificity for mammalian lysoganglioside and N-acetyl-β-D-glucosamine (GlcNAc), the dominant epitope of the group A streptococcal (GAS) carbohydrate. Chorea antibodies targeted the surface of human neuronal cells, with specific induction of calcium/calmodulin-dependent protein (CaM) kinase II activity by monoclonal antibody 24.3.1 and sera from active Chorea. Convalescent sera and sera from other streptococcal diseases in the absence of Chorea did not activate the kinase. The new evidence implicates antibody-mediated neuronal cell signaling in the immunopathogenesis of Sydenham Chorea and will lead to a better understanding of other antibody-mediated neurological disorders.
Joseph Jankovic - One of the best experts on this subject based on the ideXlab platform.
-
is benign hereditary Chorea really benign brain lung thyroid syndrome caused by nkx2 1 mutations
Movement Disorders Clinical Practice, 2019Co-Authors: Hassaan Bashir, Mered Parnes, Joseph JankovicAbstract:Background Since its localization to the NKX2-1 gene in 2002, the phenotype of the disorder historically called "benign hereditary Chorea" has been expanding beyond Chorea. Methods The phenomenology of movement disorders and other symptomatology associated with mutations in NKX2-1 were characterized after a detailed evaluation of consecutive patients evaluated in our clinic over the past 3 years. Results We studied 5 patients (3 females), ages 2 to 31 years, with confirmed pathogenic variants in NKX2-1. All patients exhibited Chorea, gross motor delay, and gait impairment. Other symptoms included neonatal respiratory failure (n = 4), cognitive deficits (n = 3), hypothyroidism (n = 4), joint laxity (n = 2), myoclonus (n = 1), hypotonia (n = 3), and seizures (n = 1). Chorea often proved refractory to medical therapies. Conclusions The phenotype associated with pathogenic variants in NKX2-1 frequently includes disabling and often medically refractory neurological and non-neurological abnormalities. We therefore suggest that the term benign hereditary Chorea be abandoned in favor of its genetic designation as NKX2-1-related disorder.
-
Chorea athetosis and ballism
Movement Disorders in Childhood (Second Edition), 2016Co-Authors: Harvey S Singer, Donald L. Gilbert, Jonathan W. Mink, Joseph JankovicAbstract:This chapter discusses the large variety of diagnoses in childhood where Chorea may be a prominent feature. Chorea is uncommon in children. It nearly always causes some interference with life activities and is perceived as involuntary by the individual. The terms “athetosis” and “ballism” designate similar movements, and are reviewed in this chapter. The most common cause of Chorea in childhood is Sydenham’s Chorea. This chapter provides a systematic approach to diagnosis and treatment of Chorea in childhood, based on childhood development, epidemiology, primary features, associated symptoms, and understanding of neuroanatomy and pathophysiology.
-
safety and efficacy of tetrabenazine and use of concomitant medications during long term open label treatment of Chorea associated with huntington s and other diseases
Tremor and other hyperkinetic movements (New York N.Y.), 2013Co-Authors: Vivienne Shen, Kathleen Clarencesmith, Christine Hunter, Joseph JankovicAbstract:Background: Although tetrabenazine, a drug that depletes presynaptic dopamine by inhibiting vesicular monoamine transporter 2 (VMAT2), was approved by the U.S. Food and Drug Administration in 2008 for the treatment of Chorea associated with Huntington’s disease (HD), there is a paucity of data on its long‐term efficacy and safety. Methods: Approximately 2,000 patients with a variety of hyperkinetic movement disorders had been treated with open‐label tetrabenazine at the Movement Disorders Clinic, Baylor College of Medicine, since 1979. Tetrabenazine was usually started at 12.5 mg/day, and the dosage was gradually increased (up to 300 mg/day). Responses were rated by the investigator 1–5, with 1 = marked Chorea reduction, excellent improvement in function; 2 = moderate Chorea reduction, very good improvement in function; 3 = fair Chorea improvement, only mild improvement in function; 4 = poor or no response for Chorea and function; and 5 = worsening Chorea, some functional deterioration. Efficacy and safety were analyzed retrospectively. Results: By 2004, 98 HD Chorea patients had received tetrabenazine for a mean of 3.1 years (range ≤1–11.4 years). Of those with valid ratings, 75% had either marked or very good responses (rating 1 or 2) at their optimal dosages. The most common adverse events occurring in ≥5% of the patients were somnolence (39%), insomnia (33%), depression (31%), accidental injury (26%), and dysphagia (19%). Efficacy and safety were comparable to results for non‐HD Chorea patients. Discussion: Tetrabenazine treatment was associated with long‐term improvement in Chorea. Adverse event rates were comparable to those reported from controlled trials.
-
Chorea and ballism.
Current opinion in neurology and neurosurgery, 1992Co-Authors: Burnett L, Joseph JankovicAbstract:: Chorea and ballism are hyperkinetic movement disorders which can be caused by a variety of conditions including metabolic abnormalities, neurodegenerative and immunologic disorders, as well as structural lesions. In addition, paroxysmal dyskinesias may be associated with Chorea. Chorea is increasingly recognized as a symptom of a variety of different conditions. The pathophysiologic mechanisms underlying choreic disorders, however, need further elucidation.