RESUMEN
Spinal muscular atrophy (SMA) is a motor neuron disease associated with progressive muscle weakness, ventilatory failure, and reduced survival. Onasemnogene abeparvovec is the first gene replacement therapy (GT) approved to treat this condition. An observational retrospective study was conducted to assess adverse events and efficacy of GT in SMA patients. Forty-one patients with SMA (58.5% females and 80.1% SMA type 1) were included. The mean age at GT dosing was 18 (±6.4) months. Thirty-six patients (87.8%) were under previous treatment with nusinersen, and 10 (24.4%) continued nusinersen after GT. Mean CHOP-INTEND increased 13 points after 6 months and this finding did not differ between groups according to nusinersen maintenance after GT (p = 0.949). Among SMA type 1 patients, 14 (46.6%) reached the ability to sit alone. Liver transaminases elevation at least two times higher than the upper limit of normal value occurred in 29 (70.7%) patients. Thrombocytopenia occurred in 13 (31.7%) patients, and one presented thrombotic microangiopathy. Older age (>2 years) was associated with more prolonged use of corticosteroids (p = 0.021). GT is effective in SMA patients, combined nusinersen after GT did not appear to add gain in motor function and older age is associated with prolonged corticosteroid use.
Asunto(s)
Terapia Genética , Oligonucleótidos , Humanos , Femenino , Masculino , Terapia Genética/métodos , Estudios Retrospectivos , Oligonucleótidos/uso terapéutico , Lactante , Brasil , Atrofia Muscular Espinal/terapia , Atrofia Muscular Espinal/genética , Resultado del Tratamiento , Preescolar , Atrofias Musculares Espinales de la Infancia/genética , Atrofias Musculares Espinales de la Infancia/terapia , Productos Biológicos/uso terapéutico , Proteínas Recombinantes de FusiónRESUMEN
Allgrove syndrome is an autosomal recessive disease mostly caused by mutations in the AAAS gene. It has variable clinical features but its cardinal features comprise the triad of achalasia, alacrimia and adrenal insufficiency. It typically develops during the first decade of life, but some cases have second and third decades onset. We describe a 25-year-old woman with Allgrove syndrome who had progressive amyotrophy, achalasia, dry eyes and adrenal insufficiency since childhood. Awareness of its neurological manifestations and multisystem features helps to shorten the time for diagnosis and allow appropriate symptomatic treatment.
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Insuficiencia Suprarrenal , Acalasia del Esófago , Insuficiencia Suprarrenal/complicaciones , Insuficiencia Suprarrenal/diagnóstico , Insuficiencia Suprarrenal/genética , Adulto , Niño , Acalasia del Esófago/complicaciones , Acalasia del Esófago/diagnóstico , Acalasia del Esófago/genética , Femenino , Humanos , MutaciónRESUMEN
BACKGROUND: Severe visual impairment is present in nearly all infants with congenital Zika syndrome (CZS); however, ocular abnormalities are present only in a subset of these infants. The purpose of this study was to characterize the visual pathway abnormalities seen on computed tomography (CT) and MRI scans in infants with CZS. METHODS: Preliminary neuroimaging information was obtained from a referred sample of 105 infants with clinical and epidemiologic data consistent with CZS in the Pernambuco state of Brazil. Subjects were excluded if Zika virus infection was not confirmed by serologic or cerebrospinal fluid studies or if images were nondiagnostic. Of the 105 subjects initially screened, head CT images adequate for interpretation were available for 54, and brain MRI images adequate for interpretation were available for 20. Four patients had both CT and MRI images. Magnetic resonance imaging and CT scans from infants with CZS were systematically reviewed for globe malformations, optic nerve and chiasmal atrophy, occipital cortical volume loss, white matter abnormalities, ventriculomegaly, and calcifications. Neuroimaging findings were correlated with measures of visual function and with ocular examinations in these infants. RESULTS: Thirty-three males and 37 females were included in the analysis. The mean age of the infants at the time of neuroimaging was 16.0 weeks (range 0 days-15.5 months), and the mean gestational age at the time of birth was 38 weeks. All patients were from the Pernambuco state of Brazil. Overall, 70 of 74 (95%) scans showed occipital volume loss, whereas 9 (12%) showed optic nerve atrophy, 3 (4%) showed chiasmal atrophy, and 1 (1%) showed an ocular calcification. Sixty-two of the infants underwent ophthalmologic examinations. A total of 34 (55%) infants had at least one documented structural ocular abnormality, and 26 (42%) had at least one structural ocular abnormality documented in both eyes. Of those with available visual acuity data, all had visual impairment. Among those with visual impairment and normal eye examinations, 100% had visual pathway abnormalities on neuroimaging, including 100% with occipital cortical volume loss, 8% with optic nerve atrophy, and 8% with chiasmal atrophy. CONCLUSION: Our results suggest that cortical visual impairment related to structural abnormalities of the occipital cortex is likely an important cause of visual impairment in children with CZS with normal eye examinations.
Asunto(s)
Hidrocefalia , Microcefalia , Infección por el Virus Zika , Virus Zika , Niño , Femenino , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Microcefalia/diagnóstico , Tomografía Computarizada por Rayos X , Vías Visuales/diagnóstico por imagen , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/diagnóstico por imagenRESUMEN
Congenital Zika virus syndrome (CZVS) is associated with severe neurological deficits. Clinical characteristics of epilepsy and the electroencephalographic (EEG) pattern in CZVS were documented in infancy. In this study, we aimed to describe the EEG findings observed during the follow-up of children with CZVS. Seventy-six EEGs of 55 children (60% female; mean age = 50 months) with confirmed CZVS were analyzed, considering the background, interictal, and ictal epileptiform discharges. Continuous (or almost continuous) epileptiform discharges during non-rapid eye movement sleep were identified in 22 (40%) patients. In 20 (90.1%) patients, the pattern was symmetrical, with an anterior predominance of the epileptiform activity. All patients with this pattern had epilepsy, which was severe in 15 (68.2%) and demanded polytherapy in 19 (86.4%). Subcortical calcifications (77.3%) and multifocal EEGs (72.8%) in earlier ages occurred more often in patients with this pattern. Other unspecific interictal EEG patterns were focal epileptiform discharges in 23 (41.8%) and multifocal activity in six (10.9%). In CZVS, continuous (or almost continuous) epileptiform discharges during sleep emerge as a pattern after the second year of life. This was associated with severe and drug-resistant epilepsy, but not necessarily with an apparent regression. Subcortical calcifications and multifocal epileptiform discharges in infancy are associated with this pattern.
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Encéfalo/fisiopatología , Epilepsia/fisiopatología , Malformaciones del Desarrollo Cortical/fisiopatología , Sueño , Infección por el Virus Zika/congénito , Infección por el Virus Zika/fisiopatología , Anticonvulsivantes/uso terapéutico , Enfermedades de los Ganglios Basales/diagnóstico por imagen , Enfermedades de los Ganglios Basales/fisiopatología , Encéfalo/diagnóstico por imagen , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/patología , Calcinosis/diagnóstico por imagen , Calcinosis/fisiopatología , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Preescolar , Progresión de la Enfermedad , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia Refractaria/fisiopatología , Electroencefalografía , Epilepsias Parciales/diagnóstico por imagen , Epilepsias Parciales/tratamiento farmacológico , Epilepsias Parciales/fisiopatología , Epilepsia/diagnóstico por imagen , Epilepsia/tratamiento farmacológico , Femenino , Humanos , Masculino , Malformaciones del Desarrollo Cortical/diagnóstico por imagen , Tamaño de los Órganos , Polimicrogiria/diagnóstico por imagen , Polimicrogiria/fisiopatología , Índice de Severidad de la Enfermedad , Síndrome , Enfermedades Talámicas/diagnóstico por imagen , Enfermedades Talámicas/fisiopatología , Infección por el Virus Zika/diagnóstico por imagenRESUMEN
We summarize the characteristics of dysphagia in 9 infants in Brazil with microcephaly caused by congenital Zika virus infection. The Schedule for Oral Motor Assessment, fiberoptic endoscopic evaluation of swallowing, and the videofluoroscopic swallowing study were used as noninstrumental and instrumental assessments. All infants had a degree of neurologic damage and showed abnormalities in the oral phase. Of the 9 infants, 8 lacked oral and upper respiratory tract sensitivity, leading to delays in initiation of the pharyngeal phase of swallowing. Those delays, combined with marked oral dysfunction, increased the risk for aspiration of food, particularly liquid foods. Dysphagia resulting from congenital Zika virus syndrome microcephaly can develop in infants >3 months of age and is severe.
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Trastornos de Deglución/etiología , Microcefalia/complicaciones , Microcefalia/virología , Complicaciones Infecciosas del Embarazo/virología , Infección por el Virus Zika/complicaciones , Brasil/epidemiología , Trastornos de Deglución/patología , Femenino , Humanos , Lactante , Microcefalia/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Infección por el Virus Zika/epidemiologíaRESUMEN
In October 2015, Zika virus (ZIKV) outbreak the Brazilian Ministry of Health (MoH). In response, the Brazilian Society of Medical Genetics established a task force (SBGM-ZETF) to study the phenotype of infants born with microcephaly due to ZIKV congenital infection and delineate the phenotypic spectrum of this newly recognized teratogen. This study was based on the clinical evaluation and neuroimaging of 83 infants born during the period from July, 2015 to March, 2016 and registered by the SBGM-ZETF. All 83 infants had significant findings on neuroimaging consistent with ZIKV congenital infection and 12 had confirmed ZIKV IgM in CSF. A recognizable phenotype of microcephaly, anomalies of the shape of skull and redundancy of the scalp consistent with the Fetal Brain Disruption Sequence (FBDS) was present in 70% of infants, but was most often subtle. In addition, features consistent with fetal immobility, ranging from dimples (30.1%), distal hand/finger contractures (20.5%), and feet malpositions (15.7%), to generalized arthrogryposis (9.6%), were present in these infants. Some cases had milder microcephaly or even a normal head circumference (HC), and other less distinctive findings. The detailed observation of the dysmorphic and neurologic features in these infants provides insight into the mechanisms and timings of the brain disruption and the sequence of developmental anomalies that may occur after prenatal infection by the ZIKV.
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Brotes de Enfermedades , Enfermedades Fetales/epidemiología , Microcefalia/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Infección por el Virus Zika/epidemiología , Anticuerpos Antivirales/líquido cefalorraquídeo , Encéfalo/anomalías , Encéfalo/virología , Brasil/epidemiología , Femenino , Enfermedades Fetales/diagnóstico por imagen , Enfermedades Fetales/patología , Feto , Humanos , Inmunoglobulina G/líquido cefalorraquídeo , Lactante , Microcefalia/complicaciones , Microcefalia/diagnóstico por imagen , Microcefalia/patología , Neuroimagen , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/patología , Síndrome , Virus Zika/crecimiento & desarrollo , Virus Zika/inmunología , Virus Zika/patogenicidad , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/diagnóstico por imagen , Infección por el Virus Zika/patologíaAsunto(s)
Epilepsia/etiología , Infección por el Virus Zika/congénito , Anticonvulsivantes/uso terapéutico , Quimioterapia Combinada , Electroencefalografía , Epilepsia/tratamiento farmacológico , Epilepsia/fisiopatología , Femenino , Humanos , Lactante , Embarazo , Complicaciones Infecciosas del Embarazo , Inducción de Remisión , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/complicacionesRESUMEN
Congenital infection with Zika virus causes microcephaly and other brain abnormalities (1). Hearing loss associated with other congenital viral infections is well described; however, little is known about hearing loss in infants with congenital Zika virus infection. A retrospective assessment of a series of 70 infants aged 0-10 months with microcephaly and laboratory evidence of Zika virus infection was conducted by the Hospital Agamenon Magalhães in Brazil and partners. The infants were enrolled during November 2015-May 2016 and had screening and diagnostic hearing tests. Five (7%) infants had sensorineural hearing loss, all of whom had severe microcephaly; however, one child was tested after receiving treatment with an ototoxic antibiotic. If this child is excluded, the prevalence of sensorineural hearing loss was 5.8% (four of 69), which is similar to that seen in association with other congenital viral infections. Additional information is needed to understand the prevalence and spectrum of hearing loss in children with congenital Zika virus infection; all infants born to women with evidence of Zika virus infection during pregnancy should have their hearing tested, including infants who appear normal at birth.
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Pérdida Auditiva/epidemiología , Transmisión Vertical de Enfermedad Infecciosa , Microcefalia/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Infección por el Virus Zika/congénito , Brasil/epidemiología , Femenino , Pérdida Auditiva/virología , Pruebas Auditivas , Humanos , Lactante , Recién Nacido , Masculino , Microcefalia/virología , Tamizaje Neonatal , Embarazo , Estudios Retrospectivos , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/transmisiónRESUMEN
Congenital Zika virus infection can cause microcephaly and severe brain abnormalities (1). Congenital Zika syndrome comprises a spectrum of clinical features (2); however, as is the case with most newly recognized teratogens, the earliest documented clinical presentation is expected to be the most severe. Initial descriptions of the effects of in utero Zika virus infection centered prominently on the finding of congenital microcephaly (3). To assess the possibility of clinical presentations that do not include congenital microcephaly, a retrospective assessment of 13 infants from the Brazilian states of Pernambuco and Ceará with normal head size at birth and laboratory evidence of congenital Zika virus infection was conducted. All infants had brain abnormalities on neuroimaging consistent with congenital Zika syndrome, including decreased brain volume, ventriculomegaly, subcortical calcifications, and cortical malformations. The earliest evaluation occurred on the second day of life. Among all infants, head growth was documented to have decelerated as early as 5 months of age, and 11 infants had microcephaly. These findings provide evidence that among infants with prenatal exposure to Zika virus, the absence of microcephaly at birth does not exclude congenital Zika virus infection or the presence of Zika-related brain and other abnormalities. These findings support the recommendation for comprehensive medical and developmental follow-up of infants exposed to Zika virus prenatally. Early neuroimaging might identify brain abnormalities related to congenital Zika infection even among infants with a normal head circumference (4).
Asunto(s)
Microcefalia/epidemiología , Infección por el Virus Zika/congénito , Infección por el Virus Zika/diagnóstico , Virus Zika/aislamiento & purificación , Brasil/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo , Estudios RetrospectivosRESUMEN
BACKGROUND: Niemann-Pick disease Type C (NP-C) is difficult to diagnose due to heterogeneous and nonspecific clinical presentation. The NP-C Suspicion Index (SI) was developed to identify patients with a high likelihood of NP-C; however, it was less reliable in patients aged <4 years. METHODS: An early-onset NP-C SI was constructed following retrospective chart review of symptom presentation in 200 patients from nine centres comprised of 106 NP-C cases, 31 non-cases and 63 controls. Statistical analyses defined strength of association between symptoms and a diagnosis of NP-C and assigned risk prediction scores to each symptom. RESULTS: Visceral symptoms were amongst the strongest predictors. Except for gelastic cataplexy and vertical supranuclear gaze palsy, central nervous system symptoms were not discriminatory in this population. Performance of the early-onset NP-C SI was superior versus the original NP-C SI in patients aged ≤4 years. CONCLUSIONS: The early-onset NP-C SI can help physicians, especially those with limited knowledge of NP-C, to identify patients aged ≤4 years who warrant further investigation for NP-C.
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Técnicas de Apoyo para la Decisión , Indicadores de Salud , Enfermedad de Niemann-Pick Tipo C/diagnóstico , Factores de Edad , Estudios de Casos y Controles , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y EspecificidadRESUMEN
Zika virus (ZIKV) infection was first reported in 2015 in Brazil as causing microcephaly and other developmental abnormalities in newborns, leading to the identification of Congenital Zika Syndrome (CZS). Viral infections have been considered an environmental risk factor for neurodevelopmental disorders outcome, such as Autism Spectrum Disorder (ASD). Moreover, not only the infection per se, but maternal immune system activation during pregnancy, has been linked to fetal neurodevelopmental disorders. To understand the impact of ZIKV vertical infection on brain development, we derived induced pluripotent stem cells (iPSC) from Brazilian children born with CZS, some of the patients also being diagnosed with ASD. Comparing iPSC-derived neurons from CZS with a control group, we found lower levels of pre- and postsynaptic proteins and reduced functional synapses by puncta co-localization. Furthermore, neurons and astrocytes derived from the CZS group showed decreased glutamate levels. Additionally, the CZS group exhibited elevated levels of cytokine production, one of which being IL-6, already associated with the ASD phenotype. These preliminary findings suggest that ZIKV vertical infection may cause long-lasting disruptions in brain development during fetal stages, even in the absence of the virus after birth. These disruptions could contribute to neurodevelopmental disorders manifestations such as ASD. Our study contributes with novel knowledge of the CZS outcomes and paves the way for clinical validation and the development of potential interventions to mitigate the impact of ZIKV vertical infection on neurodevelopment.
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Encéfalo , Células Madre Pluripotentes Inducidas , Transmisión Vertical de Enfermedad Infecciosa , Sinapsis , Infección por el Virus Zika , Virus Zika , Humanos , Infección por el Virus Zika/virología , Infección por el Virus Zika/patología , Femenino , Virus Zika/patogenicidad , Sinapsis/patología , Sinapsis/metabolismo , Encéfalo/virología , Encéfalo/patología , Embarazo , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/virología , Neuronas/virología , Neuronas/metabolismo , Neuronas/patología , Masculino , Astrocitos/virología , Astrocitos/metabolismo , Enfermedades Neuroinflamatorias/virología , Enfermedades Neuroinflamatorias/patología , Enfermedades Neuroinflamatorias/metabolismo , Complicaciones Infecciosas del Embarazo/virología , Complicaciones Infecciosas del Embarazo/patología , Brasil , Recién Nacido , Trastorno del Espectro Autista/virología , NiñoRESUMEN
Zika virus (ZIKV) infection was first associated with Central Nervous System (CNS) infections in Brazil in 2015, correlated with an increased number of newborns with microcephaly, which ended up characterizing the Congenital Zika Syndrome (CZS). Here, we investigated the impact of ZIKV infection on the functionality of iPSC-derived astrocytes. Besides, we extrapolated our findings to a Brazilian cohort of 136 CZS children and validated our results using a mouse model. Interestingly, ZIKV infection in neuroprogenitor cells compromises cell migration and causes apoptosis but does not interfere in astrocyte generation. Moreover, infected astrocytes lost their ability to uptake glutamate while expressing more glutamate transporters and secreted higher levels of IL-6. Besides, infected astrocytes secreted factors that impaired neuronal synaptogenesis. Since these biological endophenotypes were already related to Autism Spectrum Disorder (ASD), we extrapolated these results to a cohort of children, now 6-7 years old, and found seven children with ASD diagnosis (5.14 %). Additionally, mice infected by ZIKV revealed autistic-like behaviors, with a significant increase of IL-6 mRNA levels in the brain. Considering these evidence, we inferred that ZIKV infection during pregnancy might lead to synaptogenesis impairment and neuroinflammation, which could increase the risk for ASD.
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Astrocitos , Trastorno del Espectro Autista , Enfermedades Neuroinflamatorias , Sinapsis , Infección por el Virus Zika , Virus Zika , Infección por el Virus Zika/patología , Infección por el Virus Zika/metabolismo , Infección por el Virus Zika/virología , Infección por el Virus Zika/complicaciones , Trastorno del Espectro Autista/virología , Trastorno del Espectro Autista/metabolismo , Trastorno del Espectro Autista/etiología , Trastorno del Espectro Autista/patología , Humanos , Animales , Ratones , Virus Zika/fisiología , Femenino , Niño , Sinapsis/metabolismo , Sinapsis/patología , Enfermedades Neuroinflamatorias/virología , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/patología , Enfermedades Neuroinflamatorias/etiología , Astrocitos/virología , Astrocitos/metabolismo , Astrocitos/patología , Masculino , Interleucina-6/metabolismo , Interleucina-6/genética , Embarazo , Factores de Riesgo , Células Madre Pluripotentes Inducidas/virología , Células Madre Pluripotentes Inducidas/metabolismo , Brasil/epidemiología , Modelos Animales de Enfermedad , NeurogénesisRESUMEN
BACKGROUND: Spinal muscular atrophy (SMA) is a rare genetic disease that causes progressive muscle weakness and impacts motor function. The type I is the most severe presentation and affects infants before 6 months old. In addition, the instruments available for assessing motor function have limitations when applied to infants with neuromuscular diseases and significant muscle weakness. OBJECTIVE: To translate, cross-culturally adapt, and validate the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) to Brazilian Portuguese. METHODS: The present study comprised the translation, synthesis of translations, backtranslation, consolidation by a committee of experts, and test of the final version of the CHOP INTEND in 13 patients with SMA type I. We also assessed the content validity and reliability of the translated version. RESULTS: The scale was translated considering semantic, structural, idiomatic, and cultural aspects. All agreement rates were > 0.8, the overall content validity index of the instrument was 0.98, and inter-rater reliability using the intraclass correlation coefficient was 0.998. CONCLUSION: The Brazilian version of the CHOP INTEND met semantic and technical equivalence criteria with the original version and was valid and reliable for patients with SMA type I.
ANTECEDENTES: A atrofia muscular espinhal (AME) é uma doença genética rara que provoca fraqueza muscular progressiva com impacto sobre a motricidade dos pacientes. A AME tipo I é considerada o tipo mais grave e acomete lactentes antes dos 6 meses de idade. As escalas disponíveis para avaliação das aquisições motoras mostram limitações para uso com crianças pequenas com doenças neuromusculares e fraqueza importante. OBJETIVO: Realizar a tradução, adaptação transcultural e validação para a língua portuguesa do Brasil da Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND, na sigla em inglês). MéTODOS: O presente estudo seguiu as etapas de tradução, síntese das traduções, retrotradução, consolidação por comitê de especialistas e teste com 13 pacientes com AME tipo 1. Foi avaliada a validade de conteúdo e a confiabilidade do instrumento. RESULTADOS: A escala foi traduzida considerando os aspectos semânticos, estruturais, idiomáticos e culturais. Todas as taxas de concordância foram > 0,8. O índice de validade de conteúdo geral do instrumento foi de 0,98. A confiabilidade interavaliadores analisada através do coeficiente de correlação intraclasse (ICC, na sigla em inglês) demonstrou um valor de ICC = 0,998. CONCLUSãO: A versão da CHOP INTEND em português atende aos critérios de equivalência semântica e técnica em relação à versão original e apresenta validade de conteúdo e confiabilidade para seu uso na população de pacientes com AME tipo I.
Asunto(s)
Comparación Transcultural , Atrofias Musculares Espinales de la Infancia , Humanos , Lactante , Brasil , Debilidad Muscular , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , TraduccionesRESUMEN
INTRODUCTION: Congenital Zika virus syndrome is a distinct pattern of birth defects in fetuses infected by the Zika virus. It presents a broad clinical spectrum that includes occurrences of microcephaly, hypertonia, dysphagia, hyperexcitability, seizures, and arthrogryposis. Imaging findings show neuronal migration disorders. METHODOLOGY: Case reports have suggested that arthrogryposis has a neurogenic cause. We analyzed needle electromyography and nerve conduction examinations on 77 patients aged 2-24 months presenting highly probable congenital Zika virus syndrome, with or without arthrogryposis. RESULTS: All those with arthrogryposis presented with chronic muscle denervation in the electromyography examination. Similarly, children with single or reversible joint abnormalities at birth showed the same findings. Denervation in the paravertebral musculature was found in all of the children with diaphragmatic paralysis or thoracic deformities. CONCLUSIONS: We propose that congenital contractures associated with congenital Zika virus syndrome are caused by the malformation of upper and lower motor neurons during embryogenesis.
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Artrogriposis , Microcefalia , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika , Virus Zika , Embarazo , Recién Nacido , Femenino , Niño , Humanos , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/congénito , Artrogriposis/diagnóstico , Artrogriposis/complicaciones , Electromiografía/efectos adversos , Complicaciones Infecciosas del Embarazo/diagnósticoRESUMEN
[This corrects the article DOI: 10.1016/j.ymgmr.2022.100888.].
RESUMEN
SUMMARY: The congenital Zika syndrome is a new entity of a group of etiologies that can lead to microcephaly and other brain damages during pregnancy, such as toxoplasmosis, rubeola, cytomegalovirus, and herpes simplex. The Zika virus crosses the placental barrier and, predominantly, affects neuronal progenitor cells. This disruptive process results in severe cortical developmental disorder, calcifications, cortical and subcortical atrophies, and malformations of the cerebellum, brain stem, and spinal cord. Children with congenital Zika syndrome have a set of clinical findings, such as cerebral palsy, dysphagia, orthopedic deformities, visual and auditory impairment, and, rarely, hydrocephalus. Because of the severity of brain lesions, epilepsy is a common finding and a frequent cause of increased morbidity. The prevalence of epilepsy in different series of patients ranges from 37.7% to 71.4%. The aim of this study is to review the studies published so far regarding epilepsy and the EEG pattern in series of patients with congenital Zika syndrome.
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Epilepsia , Microcefalia , Infección por el Virus Zika , Virus Zika , Niño , Electroencefalografía , Epilepsia/epidemiología , Epilepsia/etiología , Femenino , Humanos , Microcefalia/epidemiología , Placenta , Embarazo , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/congénito , Infección por el Virus Zika/epidemiologíaRESUMEN
How does the auditory function of children with congenital Zika syndrome present during the first three years of life? To determine the auditory function of children with congenital Zika syndrome during the first three years of life and estimate the frequency and long-term presentation of hearing loss in this syndrome, an auditory assessment with screening and diagnostic tests was conducted. The screening test consisted of measuring the short latency ABR using click stimuli. If the ABR click indicated hearing loss, confirmation was obtained with a frequency-specific ABR (FS-ABR), in which the stimuli were tone bursts at frequencies of 500 and 2000 Hz by bone and air conduction. This case series included 107 children with confirmed congenital Zika syndrome, and the cumulative incidence of sensorineural hearing loss in the first three years of life was 9.3% (10/107). There were no cases of delayed-onset or progressive deficits in hearing. Early presentation of sensorineural hearing loss seems to occur with a higher frequency in children with congenital Zika syndrome than in the general population. Sensorineural hearing loss resulting from congenital Zika virus infection does not appear to present with delayed onset or with progressive deficits.
RESUMEN
Aromatic l-amino acid decarboxylase (AADC, EC 4.1.1.28) deficiency is a rare genetic disorder characterized by developmental delay, oculogyric crises, autonomic dysfunction and other problems, caused by biallelic mutations in the DDC gene leading to deficient activity of aromatic l-amino acid decarboxylase, an enzyme involved in the formation of important neurotransmitters, such as dopamine and serotonin. A clinical development program of gene therapy for AADC deficiency is ongoing. An important step for the success of this therapy is the early and precise identification of the affected individuals, but it has been estimated that around 90% of the cases remain undiagnosed. The availability measurement of the AADC activity is mandatory for an accurate biochemical diagnosis. Based on these statements, our objectives were to develop a liquid chromatography tandem mass spectrometry (LC-MS/MS) method suitable for the determination of the AADC activity, and to evaluate its capacity to confirm the deficiency of AADC in potential patients in Brazil. The AADC activities were measured in plasma samples of seven AADC deficient patients and 35 healthy controls, after enzymatic reaction and LC-MS/MS analysis of dopamine, the main reaction product. The results obtained showed clear discrimination between confirmed AADC deficient patients and healthy controls. The method presented here could be incorporated in the IEM laboratories for confirmation of the diagnosis of when a suspicion of AADC deficiency is present due to clinical signs and/or abnormal biomarkers, including when an increased level of 3-O-methyldopa (3-OMD) is found in dried blood spots (DBS) samples from high-risk patients or from newborn screening programs.
RESUMEN
The number of studies published on postnatal microcephaly in children with Congenital Zika Syndrome is small, clinical presentations vary and aspects of the evolution of these children remain unclarified. The present case series examined clinical characteristics and assessed the growth velocity of the head circumference, weight and height Z-scores in 23 children who developed postnatal microcephaly during follow-up in the Microcephaly Epidemic Research Group Pediatric Cohort. To estimate the change in the head circumference, weight and height Z-scores over time and compare the mean difference between sexes, we used multilevel mixed-effects linear regressions with child-specific random effects. Among these children, 60.9% (n = 14/23) presented with craniofacial disproportion, 60.9% (n = 14/23) with strabismus, 47.8% (n = 11/23) with early onset seizures, 47.8% (n = 11/23) with dysphagia and 43.5% (n = 10/23) with arthrogryposis. Of the 82.7% (n = 19/23) children who underwent neuroimaging, 78.9% (n = 15/19) presented with alterations in the central nervous system. Monthly growth velocity, expressed in Z-scores, of the head circumference was - 0.098 (95% CI % - 0.117 to - 0.080), of weight was: - 0.010 (95%-CI - 0.033 to 0.014) and of height was: - 0.023 (95%-CI - 0.046 to 0.0001). Postnatal microcephaly occurred mainly in children who had already presented with signs of severe brain damage at birth; there was variability in weight and height development, with no set pattern.