Pharmacotherapy for Sydenham's chorea: where are we and where do we need to be?

INTRODUCTION: Sydenham's chorea (SC) is the most common cause of acquired chorea in children. The existing literature describes it as a benign, self-remitting condition. However, recent evidence discloses the persistence of long-course neuropsychiatric and cognitive complications in adulthood, which imposes to redefine the concept of 'benignity' of such condition. In addition, therapies are mostly empirical and non-evidence based. AREAS COVERED: Here, we conducted an electronic exploration of the PubMed database and selected 165 relevant studies directly correlated to SC treatment. Critical data from selected articles were synthesized to provide an update on pharmacotherapy in SC, which basically consists of three pillars: antibiotic, symptomatic and immunomodulant treatments. Moreover, since SC mostly affects females with recurrences occurring in pregnancy (chorea gravidarum), we focused on the management in pregnancy. EXPERT OPINION: SC is still a major burden in developing countries. The first therapeutic strategy should be the primary prevention of group A beta-hemolytic streptococcal (GABHS) infection. Secondary antibiotic prophylaxis should be performed in every SC patient as the World Health Organization (WHO) guidelines recommend. Symptomatic or immunomodulant treatments are administered according to clinical judgment. However, a greater effort to understand SC physiopathology is needed, together with larger trials, to outline appropriate therapeutic indications.

Corea como primera manifestación de lupus eritematoso sistémico sin síndrome de anticuerpos antifosfolipídicos: reporte de caso y revisión de la bibliografía / Chorea as the first clinical manifestation of systemic lupus erythematosus without anti-phospholipid syndrome: case report and literature review

Resumen ANTECEDENTES: La corea gravídica es un padecimiento poco común, caracterizado por movimientos espontáneos irregulares, no predecibles, de duración breve, que cambian de localización sin secuencia definida, y que poseen la particularidad de ser involuntarios. En la actualidad, su incidencia se estima en 1 caso por cada 2275 embarazos. CASO CLÍNICO: Paciente de 30 años, 45 kg, talla 1.65 m, IMC 16.5, tensión arterial 110-78 mmHg, frecuencia cardiaca de 136 lpm, frecuencia respiratoria de 19 rpm, saturación de oxígeno 98%. Inició con movimientos coreicos a las 12 semanas de embarazo y titulación de anticuerpos antinucleares 1:320, anticuerpos anti-ADN de 150 UI/mL, C3 en 126 mg/dL y C4 en 31 mg/dL. Se estableció el diagnóstico de lupus eritematoso sistémico con base en los criterios de EULAR/ACR. A las 32 semanas tuvo amenaza de parto pretérmino y progresión, a pesar de la útero-inhibición, preeclampsia con criterios de severidad y manifestaciones neuropsiquiátricas con exacerbación de los movimientos coreicos. La resonancia magnética no reportó hallazgos patológicos y se descartó el síndrome de anticuerpos antifosfolipídicos secundario. Luego de la finalización del embarazo remitieron los movimientos involuntarios característicos de la corea gravídica. CONCLUSIÓN: El control prenatal en el primer trimestre es fundamental para un de-senlace favorable de las pacientes; el inicio temprano de la inmunoterapia es decisivo en los desenlaces perinatales pues disminuye la morbilidad y mortalidad asociadas. La corea es una manifestación clínica incapacitante, de ahí la importancia de identificar su causa e iniciar el tratamiento oportuno.

Abstract BACKGROUND: Chorea gravidarum is a rare condition characterised by irregular, unpredictable, spontaneous movements of short duration, changing location without defined sequence, and with the peculiarity of being involuntary. Currently, its incidence is estimated at 1 case per 2275 pregnancies. CLINICAL CASE: Patient aged 30 years, 45 kg, height 1.65 m, BMI 16.5, blood pressure 110-78 mmHg, heart rate 136 bpm, respiratory rate 19 rpm, oxygen saturation 98%. She started with choreic movements at 12 weeks of pregnancy and titration of antinuclear antibodies 1:320, anti-DNA antibodies 150 IU/mL, C3 at 126 mg/dL and C4 at 31 mg/dL. The diagnosis of systemic lupus erythematosus was established based on EULAR/ACR criteria. At 32 weeks she had threatened preterm labour and progression, despite utero-inhibition, preeclampsia with severity criteria and neuropsychiatric manifestations with exacerbation of choreic movements. MRI reported no pathological findings and secondary antiphospholipid antibody syndrome was ruled out. After termination of pregnancy the involuntary movements characteristic of chorea gravidarum subsided. CONCLUSION: Prenatal monitoring in the first trimester is essential for a favourable patient outcome; early initiation of immunotherapy is crucial for perinatal outcomes as it decreases associated morbidity and mortality. Chorea is a disabling clinical manifestation, hence the importance of identifying its cause and initiating timely treatment.

Corea gravídica secundaria a síndrome antifosfolipídico: reporte de un caso y revisión de la bibliografía / Chorea gravidarum secondary to Antiphospholipid Syndrome: Report of a case and review of the literature

Resumen ANTECEDENTES: La incidencia de la corea gravídica es de 1 caso por cada 2275 embarazos. El diagnóstico diferencial se establece con distintas enfermedades neurológicas. El tratamiento de la causa subyacente implica la curación espontánea del cuadro clínico. OBJETIVO: Reportar el caso de una paciente que inició con corea gravídica secundaria a síndrome antifosfolipídico y revisar la bibliografía al respecto. CASO CLÍNICO: Paciente de 37 años, con 28 semanas de embarazo, que consultó por alteraciones del comportamiento. Los estudios de laboratorio reportaron anticuerpos antifosfolipídicos y anti-beta 2 glicoproteína elevados en dos determinaciones separadas por 12 semanas, con ANCA y ANA negativos. En la resonancia magnética cerebral no se informaron hallazgos patológicos. Se estableció el diagnóstico de corea gravídica, secundaria a síndrome antifosfolipídico. La reacción al tratamiento con anticoagulantes y corticosteroides fue satisfactoria; en la actualidad, la paciente permanece asintomática y sin tratamiento. CONCLUSIONES: Las pruebas analíticas y de neuroimagen son útiles para establecer el origen de la corea. El tratamiento con anticoagulantes se indica para prevenir eventos trombóticos en pacientes con corea secundaria a síndrome antifosfolipídico. La eficacia de los corticosteroides en el control de los síntomas neurológicos es variable; no obstante, la paciente del caso tuvo una reacción favorable y desaparición completa de los síntomas.

Abstract BACKGROUND: Chorea gravidarum has an estimated incidence of 1:2275 pregnancies. The differential diagnosis of this entity characterized by involuntary spontaneous movements together with behavioral alterations but be made with different neurological diseases. Generally, treatment of the underlying cause involves spontaneous cure of the condition. OBJETIVES: To report the case of a patient who debuted with a chorea gravidarum secondary to antiphospholipid syndrome and to review the literature. CASE DESCRIPTION: 37-years-old patient, 28 weeks pregnant, who consulted for behavioral alterations. Laboratory test showed elevated anti phospholipid and anti-beta 2 glycoprotein antibodies in two determinations 12 weeks apart, with negative ANCA and ANA. There was no pathological finding in brain magnetic resonance. She was diagnosed with corea gravidarum secondary to antiphospholipid syndrome. She was treated effectively with anticoagulants and corticosteroids, and is currently asymptomatic and without treatment. CONCLUSIONS: Analytical and neuroimaging tests are helpful in establishing the etiology of chorea. anticoagulants are indicated to prevent thrombotic events in chorea secondary to antiphospholipid syndrome. Corticosteroids have variable efficacy in the control of neurological symptoms, although in our case complete remission of the symptoms will be overcome.

Movement disorders in pregnancy.

Movement disorders in women during pregnancy are uncommon. Therefore, high quality studies are limited, and guidelines are lacking for the treatment of movement disorders in pregnancy, thus posing a significant therapeutic challenge for the treating physicians. In this chapter, we discuss movement disorders that arise during pregnancy and the preexisting movement disorders during pregnancy. Common conditions encountered in pregnancy include but are not limited to restless legs syndrome, chorea gravidarum, Parkinson disease, essential tremor, and Huntington disease as well as more rare movement disorders (Wilson's disease, dystonia, etc.). This chapter summarizes the published literature on movement disorders and pharmacologic and surgical considerations for neurologists and physicians in other specialties caring for patients who are pregnant or considering pregnancy.

Treatment of Secondary Chorea: A Review of the Current Literature.

Background: Chorea consists of involuntary movements affecting the limbs, trunk, neck or face, that can move from one body part to another. Chorea is conceptualized as being "primary" when it is attributed to Huntington's disease (HD) or other genetic etiologies, or "secondary" when it is related to infectious, pharmacologic, metabolic, autoimmune disorders, or paraneoplastic syndromes. The mainstay of the secondary chorea management is treating the underlying causative disorder; here we review the literature regarding secondary chorea. We also discuss the management of several non-HD genetic diseases in which chorea can be a feature, where metabolic targets may be amenable to intervention and chorea reduction. Methods: A PubMed literature search was performed for articles relating to chorea and its medical and surgical management. We reviewed the articles and cross-references of pertinent articles to assess the current clinical practice, expert opinion, and evidence-based medicine to synthesize recommendations for the management of secondary chorea. Results: There are very few double-blind randomized controlled trials assessing chorea treatments regardless of etiology. Most recommendations are based on small open-label studies, case reports, and expert opinion. Discussion: Treatment of secondary chorea is currently based on expert opinion, clinical experience, and small case studies, with limited evidence-based medical data. When chorea is secondary to an underlying infection, medication, metabolic abnormality, autoimmune process, or paraneoplastic illness, the movements typically resolve following treatment of the underlying disease. Tardive dyskinesia is most rigorously studied secondary chorea with the best evidence-based medicine treatment guidelines recommending the use of pre-synaptic dopamine-depleting agents. Even though there is an insufficient pool of EBM, small clinical trials, case reports, and expert opinion are valuable for guiding treatment and improving the quality of life for patients with chorea. Highlights: There is a dearth of well-controlled studies regarding the treatment of chorea. Expert opinion and clinical experiences are fundamental in guiding chorea management and determining successful treatment. In general, secondary chorea improves with treating the underlying medical abnormality; treatments include antibiotics, antivirals, immunosuppression, dopamine depleting agents, chelation, and supportive care.

Chorea gravidarum: Case report and review of the literature / Corea Gravídica: reporte de caso y revisión de la literatura

OBJECTIVE: To present a case of chorea gravidarum and conduct a review of the published literature on the treatment for this condition, and on maternal and fetal prognosis. METHODS: Case presentation of a 16-year-old primiparous patient admitted to a Level III public hospital at 8 weeks of gestation complaining of involuntary head and limb movements and right lower limb hyperreflexia lasting three days. The patient had a history of Sydenham chorea. Treatment with antipsychotics and benzodiazepines was given to manage symptoms, and with benzathine penicillin to address the etiology, achieving control at 14 weeks. Treatment was discontinued at 35 weeks and the patient went on to have normal delivery at 39 weeks. A search was conducted in the Medline via PubMed, UptoDate, Medscape and Google Scholar databases using the terms "Pregnancy and Chorea Gravidarum". The search was limited to case reports and case series or review articles published between 2000 al 2019. RESULTS: Seven case reports and one review of the topic were found. In 4 of the 7 cases, treatment was based on haloperidol, benzodiazepines and chlorpromazine. Penicillin was used in one of two cases with a history of Sydenham chorea. Maternal and fetal prognosis was good in 6 of 7 cases, there was 1 case of intrauterine growth restriction. CONCLUSIONS: Treatment of gestation chorea is primarily expectant and the goal is to reduce symptoms. Maternal and fetal prognosis is good.

TITULO: COREA GRAVÍDICA: REPORTE DE CASO Y REVISIÓN DE LA LITERATURA. OBJETIVO: presentar un caso de corea gravídica y hacer una revisión sistemática de la literatura publicada sobre el tratamiento y pronóstico materno-fetal de la entidad. METODOS: se presenta el caso de una paciente de 16 años, primigesta, que ingresa a un hospital público de tercer nivel de complejidad, con 8 semanas de gestación, con clínica de 3 días de evolución caracterizada por movimientos involuntarios de la cabeza y las extremidades, con hiperreflexia en miembro inferior derecho. Antecedente de Corea de Sydenham. Se da tratamiento con antisicóticos y benzodiacepinas para la sintomatología y etiológico con penicilina benzatínica y control del cuadro a las 14 semanas. Suspendió el tratamiento a las 35 semanas. Parto normal a las 39 semanas. Se realizó una búsqueda en la base de datos de Medline vía PubMed, UptoDate, Medscape y Google Académico empleando los términos: "Pregnancy" and "Chorea Gravidarum". La búsqueda se limitó a reportes y series de casos o artículos de revisión, desde el año 2000 al 2019. RESULTADOS: se encontraron siete reportes de casos y una revisión de tema. El tratamiento se realizó con haloperidol benzodiacepinas y clorpromacina en cuatro de los siete casos. En uno de los dos casos con antecedentes de corea de Sydenham se utilizó penicilina. El pronóstico materno-fetal fue bueno en seis de siete casos, en un caso hubo restricción de crecimiento intrauterino. CONCLUSIONES: el tratamiento de la corea gestacional principalmente es expectante y su finalidad es disminuir la sintomatología, el pronóstico materno-fetal es bueno.

Chorea gravidarum: Case report and review of the literature / Corea gravídica: reporte de caso y revisión de la literatura

RESUMEN Objetivos: presentar un caso de corea gravídica y hacer una revisión sistemática de la literatura pu- blicada sobre el tratamiento y pronóstico materno- fetal de la entidad. Materiales y métodos: se presenta el caso de una paciente de 16 años, primigesta, que ingresa a un hospital público de tercer nivel de complejidad, con 8 semanas de gestación, con clínica de 3 días de evo- lución caracterizada por movimientos involuntarios de la cabeza y las extremidades, con hiperreflexia en miembro inferior derecho. Antecedente de Corea de Sydenham. Se da tratamiento con antisicóticos y benzodiacepinas para la sintomatología y etiológico con penicilina benzatínica y control del cuadro a las 14 semanas. Suspendió el tratamiento a las 35 semanas. Parto normal a las 39 semanas. Se realizó una búsqueda en la base de datos de Medline vía PubMed, UptoDate, Medscape y Google Académico empleando los términos: "Pregnancy" and "Chorea Gravidarum". La búsqueda se limitó a reportes y series de casos o artículos de revisión, desde el año 2000 al 2019. Resultados: se encontraron siete reportes de casos y una revisión de tema. El tratamiento se realizó con haloperidol benzodiacepinas y clorpromacina en cuatro de los siete casos. En uno de los dos casos con antecedentes de corea de Sydenham se utilizó penicilina. El pronóstico materno-fetal fue bueno en seis de siete casos, en un caso hubo restricción de crecimiento intrauterino. Conclusión: el tratamiento de la corea gestacional principalmente es expectante y su finalidad es disminuir la sintomatología, el pronóstico materno- fetal es bueno.

ABSTRACT Objectives: To present a case of chorea gravidarum and conduct a review of the published literature on the treatment for this condition, and on maternal and fetal prognosis. Materials and methods: Case presentation of a 16-year-old primiparous patient admitted to a Level III public hospital at 8 weeks of gestation complaining of involuntary head and limb movements and right lower limb hyperreflexia lasting three days. The patient had a history of Sydenham chorea. Treatment with antipsychotics and benzodiazepines was given to manage symptoms, and with benzathine penicillin to address the etiology, achieving control at 14 weeks. Treatment was discontinued at 35 weeks and the patient went on to have normal delivery at 39 weeks. A search was conducted in the Medline via PubMed, UptoDate, Medscape and Google Scholar databases using the terms "Pregnancy and Chorea Gravidarum". The search was limited to case reports and case series or review articles published between 2000 al 2019. Results: Seven case reports and one review of the topic were found. In 4 of the 7 cases, treatment was based on haloperidol, benzodiazepines and chlorpromazine. Penicillin was used in one of two cases with a history of Sydenham chorea. Maternal and fetal prognosis was good in 6 of 7 cases, there was 1 case of intrauterine growth restriction. Conclusion: Treatment of gestation chorea is primarily expectant and the goal is to reduce symptoms. Maternal and fetal prognosis is good.