RESUMO
OBJECTIVE: Roberts syndrome (RBS), also known as Roberts-SC phocomelia syndrome, is a rare autosomal recessive developmental disorder caused by mutations in the ESCO2 gene. Cardinal clinical manifestations are pre- and postnatal growth retardation and craniofacial and limb malformations. Here, we report RBS in a Chinese adolescent with novel biallelic ESCO2 variations and complex cerebrovascular diseases. METHODS: Medical history, neurological examinations, neuroimaging, and pathology were collected in the proband and the family. Whole exome sequencing (WES) with copy number variation analysis was performed to screen for genetic variations. RESULTS: The clinical features of the proband were craniofacial and limb malformations together with complex cerebrovascular diseases. She suffered ischemic stroke at 6 years old and died of cerebellar hemorrhage secondary to an aneurysm at 13 years old. Besides, neuroimaging showed the triad of leukoencephalopathy, calcifications, and cysts. Brain histopathology revealed angiomatous changes and perivascular cysts suggesting chronic small cerebral vasculopathy. Whole exome sequencing (WES) identified novel biallelic variations in the ESCO2 gene (c.1220A>T, p.H407L and c.1562delC, p.A521fs). CONCLUSIONS: We describe complex cerebrovascular diseases in Roberts syndrome caused by novel ESCO2 biallelic variations. This case expands not only the cerebral involvement in Roberts syndrome but also the disease spectrum of the neuroimaging triad with leukoencephalopathy, calcifications, and cysts.
Assuntos
Acetiltransferases , Transtornos Cerebrovasculares , Proteínas Cromossômicas não Histona , Anormalidades Craniofaciais , Anormalidades Craniofaciais/complicações , Anormalidades Craniofaciais/genética , Humanos , Feminino , Adolescente , Acetiltransferases/genética , Proteínas Cromossômicas não Histona/genética , População do Leste Asiático , Transtornos Cerebrovasculares/genéticaRESUMO
INTRODUCTION: Histiocytic necrotizing lymphadenitis, also known as Kikuchi-Fujimoto disease, is a rare benign self-limiting inflammatory disease often seen in young adults. The main clinical features are fever with cervical lymphadenopathy. Neurological complications of Kikuchi-Fujimoto disease were occasionally reported although the specific pathogenesis was not clear. The condition could be severe when encephalitis coexists. METHODS: Here we reported a young case of Kikuchi-Fujimoto disease with subsequent severe autoimmune encephalitis. RESULTS: The symmetric striatal and limbic MRI lesions combined with psycho-cognitive, epileptic symptoms supported encephalitis. Tissue-based immunofluorescence revealed widely cytoplasmic fluorescence in rat cerebellar and hippocampal neurons, which provide evidence for immune-mediated encephalitis. The clinical outcome was satisfactory after immunosuppressive therapy with MRI lesions largely disappeared. CONCLUSION: The encephalitis complication of Kikuchi disease may be autoimmune and mediated by cytotoxic T cells.
Assuntos
Encefalite , Doença de Hashimoto , Linfadenite Histiocítica Necrosante , Linfadenopatia , Encefalite/complicações , Encefalite/etiologia , Febre/complicações , Doença de Hashimoto/complicações , Linfadenite Histiocítica Necrosante/diagnóstico , Linfadenite Histiocítica Necrosante/diagnóstico por imagem , Humanos , Linfadenopatia/complicações , Linfadenopatia/diagnóstico , Adulto JovemRESUMO
Dysfunction of learning and memory is widely found in many neurological diseases. Understanding how to preserve the normal function of learning and memory will be extremely beneficial for the treatment of these diseases. However, the possible protective effect of minocycline in memory impairment is unknown. We used the well-established D-galactose rat amnesia model and two behavioral tasks, the Morris water maze and the step-down task, for memory evaluation. Western blot and PCR were used to examine the protein and mRNA levels of Arc/Arg3.1. We report that minocycline supplementation ameliorates both the spatial and fear memory deficits caused by D-galactose. We also found that Arc/Arg3.1, c-fos, and brain-derived neurotrophic factor levels are decreased in the D-galactose animal model, and that minocycline reverses the protein and mRNA levels of Arc in the hippocampus, suggesting the potential role of Arc/Arg3.1 in minocycline's neuroprotective mechanism. Our study strongly suggests that minocycline can be used as a novel treatment for memory impairment in neurological diseases.
Assuntos
Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Galactose/efeitos adversos , Transtornos da Memória/tratamento farmacológico , Minociclina/administração & dosagem , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/genética , Transtornos da Memória/metabolismo , Minociclina/farmacologia , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , RatosRESUMO
BACKGROUND: Etomidate (R-1-[1-ethylphenyl] imidazole-5-ethyl ester) is a widely used anesthetic drug that had been reported to contribute to cognitive deficits after general surgery. However, its underlying mechanisms have not been fully elucidated. In this study, we aimed to explore the neurobiological mechanisms of cognitive impairments that caused by etomidate. METHODS: A total of 30 Sprague-Dawley rats were used and divided into two groups randomly to receive a single injection of etomidate or vehicle. Then, the rats' spatial memory ability and neuronal survival were evaluated using the Morris water maze test and Nissl staining, respectively. Furthermore, we analyzed levels of oxidative stress, as well as cyclic adenosine 3',5'-monophosphate response element-binding (CREB) protein phosphorylation and immediate early gene (IEG, including Arc, c-fos, and Egr1) expression levels using Western blot analysis. RESULTS: Compared with vehicle-treated rats, the etomidate-treated rats displayed impaired spatial learning (day 4: 27.26 ± 5.33 s vs. 35.52 ± 3.88 s, t = 2.988, P = 0.0068; day 5: 15.84 ± 4.02 s vs. 30.67 ± 4.23 s, t = 3.013, P = 0.0057; day 6: 9.47 ± 2.35 s vs. 25.66 ± 4.16 s, t = 3.567, P = 0.0036) and memory ability (crossing times: 4.40 ± 1.18 vs. 2.06 ± 0.80, t = 2.896, P = 0.0072; duration: 34.00 ± 4.24 s vs. 18.07 ± 4.79 s, t = 3.023, P = 0.0053; total swimming distance: 40.73 ± 3.45 cm vs. 27.40 ± 6.56 cm, t = 2.798, P = 0.0086) but no neuronal death. Furthermore, etomidate did not cause oxidative stress or deficits in CREB phosphorylation. The levels of multiple IEGs (Arc: vehicle treated rats 100%, etomidate treated rats 86%, t = 2.876, P = 0.0086; c-fos: Vehicle treated rats 100%, etomidate treated rats 72%, t = 2.996, P = 0.0076; Egr1: Vehicle treated rats 100%, etomidate treated rats 58%, t = 3.011, P = 0.0057) were significantly reduced in hippocampi of etomidate-treated rats. CONCLUSION: Our data suggested that etomidate might induce memory impairment in rats via inhibition of IEG expression.