RESUMO
BACKGROUND: Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction activated by microglia. The potential pathological changes of SAE are complex, and the cellular pathophysiological characteristics remains unclear. This study aims to explore the ROS/TXNIP/NLRP3 pathway mediated lipopolysaccharide (LPS)-induced inflammatory response in microglia. METHODS: BV-2 cells were pre-incubated with 10 µM N-acetyl-L-cysteine (NAC) for 2 h, which were then reacted with 1 µg/mL LPS for 24 h. Western blot assay examined the protein levels of IBA1, CD68, TXNIP, NLRP3, ASC, and Cleaved Caspase-1 in BV-2 cells. The contents of inflammatory factor were detected by ELISA assay. The co-immunoprecipitation assay examined the interaction between TXNIP and NLRP3. RESULTS: LPS was confirmed to promote the positive expressions of IBA1 and CD68 in BV-2 cells. The further experiments indicated that LPS enhanced ROS production and NLRP3 inflammasome activation in BV-2 cells. Moreover, we also found that NAC partially reversed the facilitation of LPS on the levels of ROS, IL-1ß, IL-18, TXNIP, NLRP3, ASC, and Cleaved Caspase-1 in BV-2 cells. NAC treatment also notably alleviated the interaction between TXNIP and NLRP3 in BV-2 cells. CONCLUSION: ROS inhibition mediated NLRP3 signaling inactivation by decreasing TXNIP expression.
Assuntos
Proteínas de Transporte , Caspase 1 , Inflamassomos , Inflamação , Lipopolissacarídeos , Microglia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Espécies Reativas de Oxigênio , Transdução de Sinais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Microglia/metabolismo , Microglia/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Proteínas de Transporte/metabolismo , Animais , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Caspase 1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Inflamassomos/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Linhagem Celular , Acetilcisteína/farmacologia , Proteínas de Ligação ao Cálcio/metabolismo , Interleucina-1beta/metabolismo , Interleucina-18/metabolismo , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Proteínas dos Microfilamentos/metabolismo , Tiorredoxinas/metabolismo , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Encefalopatia Associada a Sepse/metabolismo , Encefalopatia Associada a Sepse/patologia , Molécula CD68RESUMO
We described a challenging case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in a young girl. Despite enduring months of reduced consciousness with ongoing antibody presence, she ultimately exhibited remarkable improvement within a 5-year follow-up period. Additionally, we conducted a concise review of relevant literature on anti-NMDAR encephalitis, with a specific focus on anti-NMDAR antibodies. Our findings enhance the clinical comprehension of anti-NMDAR encephalitis and offer valuable insights to clinicians for its management.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Autoanticorpos , Humanos , Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Feminino , Autoanticorpos/imunologia , Autoanticorpos/sangue , Receptores de N-Metil-D-Aspartato/imunologia , Criança , Transtornos da Consciência/etiologia , Transtornos da Consciência/imunologiaRESUMO
INTRODUCTION: Epilepsy, a prevalent neurodegenerative disorder, profoundly impacts the physical and mental well-being of millions globally. Historically, antiseizure drugs (ASDs) have been the primary treatment modality. However, despite the introduction of novel ASDs in recent decades, a significant proportion of patients still experiences uncontrolled seizures. AREAS COVERED: The rapid advancement of nanomedicine in recent years has enabled precise targeting of the brain, thereby enhancing therapeutic efficacy for brain diseases, including epilepsy. EXPERT OPINION: Nanomedicine holds immense promise in epilepsy treatment, including but not limited to enhancing drug solubility and stability, improving drug across blood-brain barrier, overcoming resistance, and reducing side effects, potentially revolutionizing clinical management. This paper provides a comprehensive overview of current epilepsy treatment modalities and highlights recent advancements in nanomedicine-based drug delivery systems for epilepsy control. We discuss the diverse strategies used in developing novel nanotherapies, their mechanisms of action, and the potential advantages they offer compared to traditional treatment methods.
Assuntos
Anticonvulsivantes , Barreira Hematoencefálica , Sistemas de Liberação de Medicamentos , Epilepsia , Nanomedicina , Humanos , Nanomedicina/métodos , Epilepsia/tratamento farmacológico , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Animais , Barreira Hematoencefálica/metabolismo , Nanopartículas , Solubilidade , Estabilidade de MedicamentosRESUMO
BACKGROUND: Although previous studies show that microRNAs (miRNAs) can potentially be used as diagnostic markers for epilepsy, there are very few analyses of pediatric epilepsy patients. METHODS: miRNA profiles using miRNA-seq was performed on plasma samples from 14 pediatric epileptic patients and 14 healthy children. miRNA miR-27a-3p that were significantly changed between two groups were further evaluated. The potential target genes of miR-27a-3p were screened through unbiased mRNA-seq and further validated using Western blot and immunohistochemistry in HEK-293T cells and in the brains of mice with epilepsy induced by lithium chloride-pilocarpine. RESULTS: We found 82 upregulated and 76 downregulated miRNAs in the plasma from pediatric patients compared with controls (p < 0.01), of which miR-27a-3p exhibited a very low p value (p < 0.0001) and validated in additional plasma samples. Two genes, GOLM1 and LIMK1, whose mRNA levels were decreased (p < 0.001) with the increase of miR-27a-3p were further validated in both HEK-293T cells and in epileptic mice. CONCLUSIONS: MiR-27a-3p exhibits potential as a diagnostic and therapeutic marker for epilepsy. We postulate that additional studies on the downstream targets of miR-27a-3p will unravel its roles in epileptogenesis or disease progression. IMPACT: A total of 158 differentially expressed miRNAs were detected in plasma between epileptic and control children. Plasma miR-27a-3p was one of the miRNAs with a low p value. GOLM1 and LIMK1 were validated as downstream target genes of miR-27a-3p. miR-27a-3p has potential as a diagnostic and therapeutic marker for epilepsy.
Assuntos
Epilepsia , MicroRNAs , Humanos , Camundongos , Animais , Criança , MicroRNAs/genética , Epilepsia/genética , Biomarcadores , Encéfalo , RNA Mensageiro , Quinases Lim , Proteínas de MembranaRESUMO
Cerebral adrenoleukodystrophy (CALD) is a fatal genetic disease characterized by rapid, devastating neurological decline, with a narrow curative treatment window in the early stage. Non-canonical splice-site (NCSS) variants can easily be missed during genomic DNA analyses, and only a few of them in ABCD1 have been explored. Here, we studied a Chinese patient with clinical features similar to those of early-stage CALD but with a negative molecular diagnosis and a sibling who had presumably died of CALD. Trio-based whole-exome sequencing (trio-WES) and RNA sequencing (RNA-Seq) revealed a novel hemizygote NCSS variant c.901-25_901-9 del in ABCD1 intron 1, resulting in a complex splicing pattern. The in vitro minigene assay revealed that the c.901-25_901-9 del construct contained two aberrant transcripts that caused skipping of exon 2 and a small 48-bp deletion on left of the same exon. We identified a novel NCSS variant, that extends the spectrum of the known ABCD1 variants, and demonstrated the pathogenicity of this gene variant. Our findings highlight the importance of combining RNA-Seq and WES techniques for prompt diagnosis of leukodystrophy with NCSS variants.
RESUMO
The blood-brain barrier (BBB) is an important physiological barrier of the human body contributing to maintaining brain homeostasis and normal function. Hypoxic-ischemic (HI)-related brain injury is one of the main causes of neonatal acute morbidity and chronic disability. The previous research of our group confirmed that there was serious BBB destruction during HI brain injury. However, at present, the protection strategy of BBB is very limited, and further research on the protection mechanism is warranted. Indole-3-propionic acid (IPA) is a bacterial metabolism with anti-inflammatory and antioxidant properties, having neuroprotective effects and protective effects on the mucosal barrier. However, the role of IPA in BBB is not clear. In this research, we demonstrated the protective effect of IPA on BBB disruption from HI brain injury and hypothesized that it involves the amelioration of inflammation, oxidative stress, and MMP activation, thereby inhibiting apoptosis of rat brain microvascular endothelial cells (rBMECs). We demonstrated that expression levels of several inflammatory markers, including iNOS, TNF-α, IL-6, and IL-1ß, were significantly increased from HI damage or OGD injury. However, IPA treatment inhibited the increase significantly. Moreover, we demonstrated that IPA reduced intracellular ROS levels and MMP activation in rBMECs from OGD injury. Further research on the underlying detailed molecular mechanisms suggested that IPA attenuates inflammation by inhibiting NF-κB signaling. Finally, we investigated the mechanism of the relationship between PXR activation and NF-κB inhibition. The results suggested overexpression of PXR in rBMECs could significantly counteract the decrease of junction proteins and downregulate the increased p-IκB-α and p-NF-κB from OGD injury. However, the protective effects of IPA were reversed by antagonists of the PXR. Taken together, IPA might mitigate HI-induced damage of the BBB and the protective effect may be exerted through modulating the PXR signaling pathway.
Assuntos
Lesões Encefálicas , Hipóxia-Isquemia Encefálica , Fármacos Neuroprotetores , Animais , Animais Recém-Nascidos , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Barreira Hematoencefálica/metabolismo , Lesões Encefálicas/metabolismo , Células Endoteliais/metabolismo , Humanos , Hipóxia-Isquemia Encefálica/metabolismo , Indóis/metabolismo , Indóis/farmacologia , Inflamação/metabolismo , Interleucina-6 , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Propionatos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Purpose: Few studies have evaluated hyponatremia management in children with bacterial meningitis (BM). Thus, we aimed to describe variations in clinical practice, the effectiveness of sodium management, and adverse outcomes in children with BM and hyponatremia. Methods: This retrospective cross-sectional study conducted at a tertiary institution analyzed participants' demographic, clinical, and sodium-altering treatment data. The sodium trigger for treatment was defined as pretreatment sodium level, with response and overcorrection defined as increments of ≥5 and >10 mmol/L after 24 h, respectively. Results: This study enrolled 364 children with BM (age: <16 years; 215 boys). Hyponatremia occurred in 62.1% of patients, among whom 25.7% received sodium-altering therapies; 91.4% of those individuals had moderate/severe hyponatremia. Monotherapy was the most common initial hyponatremia treatment. After 24 h of treatment initiation, 82.4% of the patients responded. Logistic regression analyses revealed that ΔNa24 <5 mmol/L [odds ratio (OR) 15.52, 95% CI 1.71-141.06, p = 0.015] and minimum Glasgow Coma Scale (GCS) score ≤ 8 (OR 11.09, 95% CI 1.16-105.73, p = 0.036) predicted dysnatremia at 48 h after treatment initiation. Although rare, persistent moderate/severe hyponatremia or hypernatremia at 48 h after treatment initiation was associated with a high mortality rate (57.1%). Conclusion: This study found that most cases of hyponatremia responded well to various treatments. It is important to identify and institute appropriate treatment early for moderate or severe hyponatremia or hypernatremia in children with BM. This study was limited by its non-randomized nature.
RESUMO
A series of neurological manifestations such as intellectual disability and epilepsy are closely related to hypomagnesemia. Cyclin M2 (CNNM2) proteins, as a member of magnesium (Mg2+) transporters, were found along the basolateral membrane of distal renal tubules and involved in the reabsorption of Mg2+. Homozygous and heterozygous variants in CNNM2 reported so far were responsible for a variable degree of hypomagnesemia, several of which also showed varying degrees of neurological phenotypes such as intellectual disability and epilepsy. Here, we report a de novo heterozygous CNNM2 variant (c.2228C > T, p.Ser743Phe) in a Chinese patient, which is the variant located in the cyclic nucleotide monophosphate-binding homology (CNBH) domain of CNNM2 proteins. The patient presented with mild intellectual disability and refractory epilepsy but without hypomagnesemia. Thus, we reviewed the literature and analyzed the phenotypes related to CNNM2 variants, and then concluded that the number of variant alleles and the changed protein domains correlates with the severity of the disease, and speculated that the CNBH domain of CNNM2 possibly plays a limited role in Mg2+ transport but a significant role in brain development. Furthermore, it can be speculated that neurological phenotypes such as intellectual disability and seizures can be purely caused by CNNM2 variants.
RESUMO
Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in children. The orexigenic hormone ghrelin is important in neuroprotection and neurodevelopment, which may play an important role in psychopathogenesis of ADHD. This study aimed to systematically investigate the genomic and pharmacological manipulations of ghrelin functioning in ADHD-like symptoms in zebrafish models and validated the effects of ghrelin polymorphisms in human subjects with ADHD. We firstly generated ghrelinΔ/Δ zebrafish mutant, which displayed hyperactive, attention deficit-like and impulsive-like behaviors, as well as endophenotypes, mimicking human ADHD. GhrelinΔ/Δ zebrafish exhibited downregulated expression levels of wnt1, wnt3a, wnt5a that are critical for dopaminergic neuron development to possibly regulate their number and spatial organization. Pharmacological blockade of wnt signaling with XAV939 induced a reduced moving activity and less dopaminergic neurons; whereas, wnt agonist SB415286 rescued hyperactivity and dopaminergic neuron loss in ghrelinΔ/Δ zebrafish. In addition, we further identified and validated a SNP, rs696217, on orexigenic hormone preproghrelin/ghrelin (T408T, Met72Met) to be associated with a higher risk of ADHD in a case-controlled association study with 248 subjects with ADHD and 208 subjects of healthy controls. Together, our results reveal a novel endogenous role for orexigenic hormone ghrelin in ADHD, which provides insights into genetic regulation and drug screens for the identification of novel treatments of ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Animais , Transtorno do Deficit de Atenção com Hiperatividade/genética , Criança , Neurônios Dopaminérgicos , Grelina , Humanos , Comportamento Impulsivo , Peixe-ZebraRESUMO
Background: Hyponatremia has frequently been described as a common complication associated with bacterial meningitis, though its frequency and clinical course in children with bacterial meningitis are unclear. The present study aimed to investigate the frequency, clinical characteristics, and prognosis associated with pediatric hyponatremia due to bacterial meningitis. Methods: We performed a retrospective review of children with bacterial meningitis provided with standard care. One hundred seventy-five children were included. We documented all participants' symptoms and signs, laboratory and microbiological data, radiological findings, and complications that occurred during their hospital admission. Disease severity was determined using the maximum Pediatric Cerebral Performance Category (PCPC) and minimum Glasgow Coma Scale (GCS). Residual deficits were assessed using PCPC at discharge. Results: Hyponatremia (<135 mmol/L) was seen in 116 (66.4%) of the patients assessed and was classified as mild (130-135 mmol/L) in 77, moderate (125-129 mmol/L) in 26, and severe (<125 mmol/L) in 13. Hyponatremia was associated with a shorter duration of symptoms before admission, higher CSF white cell counts, and a longer duration of hospitalization. Moderate and severe hyponatremia were associated with an increase in convulsions, impaired consciousness, altered CSF protein levels, higher maximum PCPC scores, and lower minimum GCS scores. Severe hyponatremia was further associated with the development of systemic complications including shock, multiple organ dysfunction syndrome, respiratory failure requiring mechanical ventilation, and an increase in poor outcome (PCPC ≥ 2). Hyponatremia was not associated with the development of neurologic complications. Logistic regression analyses revealed that convulsions (OR 12.09, 95% CI 2.63-56.84) and blood glucose levels > 6.1 mmol/L (OR 8.28, 95% CI 1.65-41.60) predicted severe hyponatremia. Conclusion: Hyponatremia occurred in 66.4% of the assessed pediatric bacterial meningitis patients. Moderate and severe hyponatremia affected the severity of pediatric bacterial meningitis. Only severe hyponatremia affected the short-term prognosis of patients with pediatric bacterial meningitis. We recommend that patients with pediatric bacterial meningitis who exhibit convulsions and increased blood glucose levels should be checked for severe hyponatremia. Further studies are needed to evaluate the effectiveness of treatment of hyponatremia.
RESUMO
Reserpine is widely used for treatment of hypertension and schizophrenia. As a specific inhibitor of monoamine transporters, reserpine is known to deplete monoamine neurotransmitters and cause decreased movement symptoms. However, how zebrafish larvae respond to reserpine treatment is not well studied. Here we show that swimming distance and average velocity are significantly reduced after reserpine exposure under various stimulatory conditions. Using liquid chromatograph-mass spectrometer analysis, decreased levels of monoamines (e.g. dopamine, noradrenaline, and serotonin) were detected in reserpine-treated larvae. Moreover, reserpine treatment significantly reduced the number of dopaminergic neurons, which was identified with th (Tyrosine Hydroxylase) in situ hybridization in the preoptic area. Interestingly, dopaminergic neuron development-associated genes, such as otpa, otpb, wnt1, wnt3, wnt5 and manf, were downregulated in reserpine treated larvae. Our data indicates that 2â¯mg/L reserpine exposure induces dopaminergic neuron damage in the brain, demonstrating a chemical induced depression-like model in zebrafish larvae for future drug development.
Assuntos
Neurônios Dopaminérgicos/efeitos dos fármacos , Larva/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Reserpina/toxicidade , Peixe-Zebra , Animais , Monoaminas Biogênicas/metabolismo , Neurônios Dopaminérgicos/patologia , Embrião não Mamífero/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Larva/metabolismo , Luz , Locomoção/efeitos dos fármacos , Fatores de Crescimento Neural/genética , Som , Proteína Wnt-5a/genética , Proteína Wnt1/genética , Proteína Wnt3A/genética , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genéticaRESUMO
The endothelial cell (EC) barrier disruption has been implicated in vascular leakage and pulmonary edema. Many reports have shown that the EC barrier dysfunction is regulated by the sphingosine-1-phophate (S1P)/S1P receptor-1 (S1PR1) axis. Identifying downstream effectors for the S1P/S1PR1 axis in pulmonary vasculature has been limited by mixed populations in vitro cultures that do not retain physiological EC phenotype and complex of tedious proteomics. In this study, we used a combination of in vivo biotinylation and liquid chromatograph tandem mass spectrometry on three mouse models of S1pr1 expression, namely normal, knockout (KO) and high, to identify EC membrane proteins whose cell-surface expression is S1pr1-dependent. EC-specific KO of S1pr1 caused severe pulmonary vascular disruption and reduction of many membrane proteins on ECs. Using the MaxQuant software we were able to identify novel membrane targets of S1pr1, for instance, Cd105 and Plvap, by comparison with their membrane expressions among the three EC model systems. Moreover, regulation of Cd105 and Plvap by S1pr1 were validated with Western blot and immunostaining in vivo and in vitro. Our data suggest that S1pr1 dictates cell-surface localization of several apical membrane proteins in ECs. Our results are insightful for development of novel therapeutics to specifically target EC barrier function.
Assuntos
Membrana Celular/metabolismo , Endoglina/metabolismo , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Modelos Biológicos , Receptores de Esfingosina-1-Fosfato/metabolismo , Animais , Linhagem Celular , Membrana Celular/genética , Endoglina/genética , Células Endoteliais/citologia , Camundongos , Camundongos Knockout , Receptores de Esfingosina-1-Fosfato/genéticaRESUMO
RATIONALE: Pantothenate kinase-associated neurodegeneration (PKAN) represents an autosomal recessive hereditary disease. In this report, a PANK2 gene mutation in a Chinese child was identified, as well as detections of PKAN among his family members. Our findings exposed a world-wide novel compound heterozygous mutation. PATIENT CONCERNS: We described a 6-year-old male patient with PKAN, exhibiting involuntary movement for a period of 1.5 years, as well as feeding difficulties for 2 weeks. DIAGNOSIS: Due to brain computed tomography and magnetic resonance imaging results, and patient behavior, the attending physician suspected a hereditary effect. INTERVENTIONS: The patient sample underwent high-throughput sequencing. Subsequently, his parents and sister were screened for the mutations identified in the patient genome. OUTCOMES: High-throughput sequencing revealed a novel complex heterozygous mutation of the PANK2 gene, which was detected in the second and fourth exons, c.A650G, and c.T1341G, respectively, resulting in amino acid alterations (p.D217G and p.D447E, respectively). The child's father was confirmed to possess a heterozygous c.A650G mutation, while his mother was heterozygous for the c.T1341G mutation. LESSONS: The key finding of the study encompassed the detection of a novel PANK2 gene mutation in a child of Chinese ethnicity with PKAN. The PANK2 gene c.A650G, as well as c.T1341G, mutations may be potential mutation hotspots in children with PKAN in Mainland China.
Assuntos
Doenças dos Gânglios da Base/genética , Calcinose/genética , Análise Mutacional de DNA , Triagem de Portadores Genéticos , Neurodegeneração Associada a Pantotenato-Quinase/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Doenças dos Gânglios da Base/diagnóstico , Doenças dos Gânglios da Base/etnologia , Calcinose/diagnóstico , Calcinose/etnologia , Criança , China , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imageamento por Ressonância Magnética , Masculino , Neurodegeneração Associada a Pantotenato-Quinase/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
The use of botulinum neurotoxin serotype A (BoNT-A) injections for the treatment of orofacial dyskinesia secondary to anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is rarely reported. Here, we report a case of an urgent, successful management of severe orofacial dyskinesia in an 8-year-old girl with anti-NMDAR encephalitis using BoNT-A injection. The patient presented with de novo unilateral paroxysmal movement disorder progressing to generalized dystonia and repetitive orofacial dyskinesia. Diagnosis was confirmed by the presence of NMDAR antibodies in serum and cerebrospinal fluid. The orofacial dyskinesia worsened despite the aggressive use of first-line immunotherapy and second-line immunotherapy (rituximab), and resulted in a potentially fatal self-inflicted oral injury. We urgently attempted symptomatic management using BoNT-A injections in the masseter, and induced muscle paralysis using vecuronium. The patient's severe orofacial dyskinesia was controlled. We observed the effects of the BoNT-A injections and a tapering off of the effects of vecuronium 10 days after the treatment. The movement disorder had improved significantly 4 weeks after the first administration of rituximab. The injection of BoNT-A into the masseter may be an effective treatment for medically refractory orofacial dyskinesia in pediatric patients with anti-NMDAR encephalitis. We propose that the use of BoNT-A injections should be considered early to avoid self-inflicted oral injury due to severe refractory orofacial dyskinesia in patients with anti-NMDAR encephalitis.
RESUMO
RATIONALE: The respective involvements of both the thalamus and exhibitionism in cerebral X-linked adrenoleukodystrophy (X-ALD) have not been reported. PATIENT CONCERNS: An 11-year-old boy initially presented with exhibitionism and progressive neurobehavioral symptoms. He subsequently developed transient urinary and fecal incontinence, and an unwillingness to eat or communicate. DIAGNOSES: We conducted contrast-enhanced brain magnetic resonance imaging (MRI), which revealed symmetrical altered signal intensities in bilateral frontal white matter, the basal ganglia, and dorsal thalami, as well as a peripheral rim of contrast enhancement. Diagnosis of adolescent cerebral X-ALD was confirmed on the basis of next generation genetic sequencing analysis. INTERVENTIONS: We initiated the patient on hormonal replacement therapy. OUTCOMES: We observed rapidly progressive neurologic deterioration in this patient, and the boy fell into a vegetative state 10 months after discharge. LESSONS: We recommend that physicians should not disregard X-ALD in patients with isolated psychiatric symptoms, including hypersexual behavior. The combination of detailed clinical evaluation, MRI, and next generation genetic sequencing can expedite the diagnostic process of atypical variant of X-ALD.
Assuntos
Adrenoleucodistrofia/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Exibicionismo/etiologia , Adrenoleucodistrofia/genética , Adrenoleucodistrofia/patologia , Adrenoleucodistrofia/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Encéfalo/patologia , Criança , Exibicionismo/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , NeuroimagemRESUMO
OBJECTIVE: To study the prevalence and clinical features of febrile convulsion (FC) among pupils in the Wenzhou region, Zhejiang Province, China. METHODS: Using a random stratified cluster sampling method, 6406 children under 12 years from two primary schools of urban areas and two primary schools of rural areas were surveyed. RESULTS: The prevalence of FC was 3.67% (235/6406). Most children (75.7%) experienced their first onset of FC at 6 months to 3 years of age (median: 16 months). The seizures were generalized (95.3%, 224/235), with a duration of less than 10 minutes (86.4%, 203/235). FC was developed into epilepsy in 13 children (5.5%) who all suffered from complex FC. Relapses were noted in 88 cases (37.4%), among whom 38 patients had only 1 recurrence and 50 patients had 2 or more relapses. EEG was performed in 200 cases, among whom 12(6.0%) showed abnormalities. CONCLUSIONS: The prevalence of FC is 3.67% among pupils in the Wenzhou region. The seizures are generalized, with a short duration. A part of complex FC can be developed into subsequent epilepsy.