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USH2A variants are the most common cause of Usher syndrome type 2, characterized by congenital sensorineural hearing loss and retinitis pigmentosa (RP), and also contribute to autosomal recessive non-syndromic RP. Several treatment strategies are under development; however, sensitive clinical trial endpoint metrics to determine therapeutic efficacy have not been identified. In the present study, we have performed longitudinal retrospective examination of the retinal and auditory symptoms in (i) 56 biallelic molecularly confirmed USH2A patients and (ii) ush2a mutant zebrafish to identify metrics for the evaluation of future clinical trials and rapid preclinical screening studies. The patient cohort showed a statistically significant correlation between age and both rate of constriction for the ellipsoid zone length and hyperautofluorescent outer retinal ring area. Visual acuity and pure tone audiograms are not suitable outcome measures. Retinal examination of the novel ush2au507 zebrafish mutant revealed a slowly progressive degeneration of predominantly rods, accompanied by rhodopsin and blue cone opsin mislocalization from 6 to 12 months of age with lysosome-like structures observed in the photoreceptors. This was further evaluated in the ush2armc zebrafish model, which revealed similar changes in photopigment mislocalization with elevated autophagy levels at 6 days post fertilization, indicating a more severe genotype-phenotype correlation and providing evidence of new insights into the pathophysiology underlying USH2A-retinal disease.
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Proteínas da Matriz Extracelular/genética , Perda Auditiva Neurossensorial/genética , Retina/fisiopatologia , Retinose Pigmentar/genética , Síndromes de Usher/genética , Adolescente , Adulto , Idoso , Animais , Autofagia/genética , Modelos Animais de Doenças , Eletrorretinografia , Feminino , Estudos de Associação Genética , Genótipo , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Opsinas/genética , Retina/diagnóstico por imagem , Retina/metabolismo , Células Fotorreceptoras Retinianas Cones/metabolismo , Células Fotorreceptoras Retinianas Cones/patologia , Retinose Pigmentar/fisiopatologia , Rodopsina/genética , Opsinas de Bastonetes/genética , Síndromes de Usher/diagnóstico por imagem , Síndromes de Usher/patologia , Acuidade Visual/genética , Acuidade Visual/fisiologia , Adulto Jovem , Peixe-Zebra/genéticaRESUMO
Pathogenic mutations in USH2A are a leading cause of visual loss secondary to non-syndromic or Usher syndrome-associated retinitis pigmentosa (RP). With an increasing number of RP-targeted clinical trials in progress, we sought to evaluate the photoreceptor topography underlying patterns of loss observed on clinical retinal imaging to guide surrogate endpoint selection in USH2A retinopathy. In this prospective cross-sectional study, twenty-five patients with molecularly confirmed USH2A-RP underwent fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO) retinal imaging. Analysis comprised measurement of FAF horizontal inner (IR) and outer (OR) hyperautofluorescent ring diameter; SD-OCT ellipsoid zone (EZ) and external limiting membrane (ELM) width, normalised EZ reflectance; AOSLO foveal cone density and intact macular photoreceptor mosaic (IMPM) diameter. Thirty-two eyes from 16 patients (mean age ± SD, 36.0 ± 14.2 years) with USH2A-associated Usher syndrome type 2 (n = 14) or non-syndromic RP (n = 2) met the inclusion criteria. Spatial alignment was observed between IR-EZ and OR-ELM diameters/widths (p < 0.001). The IMPM border occurred just lateral to EZ loss (p < 0.001), although sparser intact photoreceptor inner segments were detected until ELM disruption. EZ width and IR diameter displayed a biphasic relationship with cone density whereby slow cone loss occurred until retinal degeneration reached ~1350 µm from the fovea, beyond which greater reduction in cone density followed. Normalised EZ reflectance and cone density were significantly associated (p < 0.001). As the strongest correlate of cone density (p < 0.001) and best-corrected visual acuity (p < 0.001), EZ width is the most sensitive biomarker of structural and functional decline in USH2A retinopathy, rendering it a promising trial endpoint.
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Retinose Pigmentar , Síndromes de Usher , Biomarcadores , Estudos Transversais , Proteínas da Matriz Extracelular/genética , Humanos , Estudos Prospectivos , Retinose Pigmentar/diagnóstico por imagem , Retinose Pigmentar/genética , Tomografia de Coerência Óptica/métodos , Síndromes de Usher/diagnóstico por imagem , Síndromes de Usher/genética , Acuidade VisualRESUMO
Choroideremia (CHM) is an x-linked recessive chorioretinal dystrophy, with 30% caused by nonsense mutations in the CHM gene resulting in an in-frame premature termination codon (PTC). Nonsense-mediated mRNA decay (NMD) is the cell's natural surveillance mechanism that detects and destroys PTC-containing transcripts, with UPF1 being the central NMD modulator. NMD efficiency can be variable amongst individuals with some transcripts escaping destruction, leading to the production of a truncated non-functional or partially functional protein. Nonsense suppression drugs, such as ataluren, target these transcripts and read-through the PTC, leading to the production of a full length functional protein. Patients with higher transcript levels are considered to respond better to these drugs, as more substrate is available for read-through. Using Quantitative reverse transcription PCR (RT-qPCR), we show that CHM mRNA expression in blood from nonsense mutation CHM patients is 2.8-fold lower than controls, and varies widely amongst patients, with 40% variation between those carrying the same UGA mutation [c.715 C>T; p.(R239*)]. These results indicate that although NMD machinery is at work, efficiency is highly variable and not wholly dependent on mutation position. No significant difference in CHM mRNA levels was seen between two patients' fibroblasts and their induced pluripotent stem cell-derived retinal pigment epithelium. There was no correlation between CHM mRNA expression and genotype, phenotype or UPF1 transcript levels. NMD inhibition with caffeine was shown to restore CHM mRNA transcripts to near wild-type levels. Baseline mRNA levels may provide a prognostic indicator for response to nonsense suppression therapy, and caffeine may be a useful adjunct to enhance treatment efficacy where indicated.
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Coroideremia/tratamento farmacológico , Degradação do RNAm Mediada por Códon sem Sentido/genética , RNA Helicases/genética , RNA Mensageiro/sangue , Transativadores/genética , Cafeína/administração & dosagem , Coroideremia/sangue , Coroideremia/genética , Coroideremia/fisiopatologia , Códon sem Sentido/genética , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Degradação do RNAm Mediada por Códon sem Sentido/efeitos dos fármacos , Oxidiazóis/administração & dosagem , Fenótipo , Células-Tronco Pluripotentes/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismoRESUMO
INTRODUCTION: Although monkeypox-related ophthalmic disease (MPXROD) is rare, visual impairing complications have been reported. At present, tecovirimat is the standard-of-care antiviral treatment. In this MPXROD case, the effect of tecovirimat was assessed with PCR analysis of tear samples and concurrent monitoring of inflammation with laser flare photometry (LFP). CASE DESCRIPTION: The patient presented with a palpebral lesion and a corneal ulcer in his right eye, with complete absence of the corneal epithelium, high intraocular pressure and anterior uveitis. MPXV-DNA was detected in tear samples with real-time PCR (RT-PCR). A total volume of 0.5 ml tear-wash was aspirated from the inferior fornix, following instillation of saline onto the ocular surface. In addition, LFP was used to quantify inflammation in both eyes. Viral load in tear samples was detected prior to treatment initiation. In the left eye, tear samples tested negative for MPXV-DNA one week post-treatment while MPXV-DNA was still detected in the right eye, before reaching undetectable levels four weeks post-treatment. Objective quantification of anterior chamber inflammation through LFP demonstrated gradual decrease that was more pronounced in the affected right eye and coincided with the clinical improvement of the corneal ulcer. CONCLUSIONS: This case of Mpox related corneal ulcer with associated uveitis manifests the feasibility of monitoring the antiviral effect of tecovirimat with virus detection in tear samples and LFP. Our observations indicate that tecovirimat resulted in viral load reduction in both eyes. RT-PCR MPXV detection in tear samples and LFP represent noninvasive tools that could assist with treatment response monitoring.
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PURPOSE: To measure aqueous flare levels in treatment naïve eyes suffering from wet age- related macular degeneration (wAMD) treated with intravitreal brolucizumab. METHODS: Patients with treatment naïve wAMD in one eye were prospectively enrolled. Flare levels were measured with laser flare photometry at baseline, 1 day and 1 month after each of the 3 monthly injections during the loading phase. RESULTS: Twenty-two eyes from 22 patients aged 76.7 ± 6.0 years were enrolled. Flare values were 10.6 ± 3.7 photons/msec at baseline and 12.6 ± 5.8 photons/msec at the last follow up visit, 1 month after the third injection (p = 0.289, repeated measures ANOVA). The mean change in flare after the first injection was 4.2 ± 3.6. photons/msec, 6.6 ± 8.9 photons/msec after the 2nd and 8.6 ± 20.8 photons/msec after the 3rd injection (p = 0.640, repeated measures ANOVA). No patient had clinical signs of intraocular inflammation. CONCLUSIONS: Eyes receiving brolucizumab injections for wAMD showed similar flare at baseline, during and 1 month after completion of three-monthly intravitreal injections. There was no evidence of subclinical inflammation during the loading phase of brolucizumab based on laser flare photometry measurements.
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PURPOSE: The ocular manifestations of Monkeypox virus (Mpox) infection remain incompletely characterized. Our goal is to present a case series of non-healing corneal ulcers with associated uveitis caused by Mpox infection as well as management recommendations for Mpox-related ophthalmic disease (MPXROD). METHODS: Retrospective case series. RESULTS: Two male patients with recent hospitalization for systemic Mpox infection presented with non-healing corneal ulcer associated with anterior uveitis and severe IOP elevation. Despite initiation of conservative medical treatment including corticosteroid treatment for uveitis, in both cases, there was clinical progression with enlarging cornea lesions. Both cases received oral tecovirimat with complete healing of the corneal lesion. CONCLUSIONS: Corneal ulcer and anterior uveitis are rare complications of Mpox infection. Although Mpox disease is generally anticipated to be self-limited, tecovirimat may be an effective intervention in poorly healing Mpox keratitis. Corticosteroids should be used with caution in Mpox uveitis, as they might lead to worsening infection.
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Doenças da Córnea , Úlcera da Córnea , Mpox , Uveíte Anterior , Uveíte , Humanos , Masculino , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/tratamento farmacológico , Estudos Retrospectivos , BenzamidasRESUMO
Pediatric high-grade gliomas (pHGGs) are heterogeneous, diffuse, and highly infiltrative tumors with dismal prognosis. Aberrant post-translational histone modifications with elevated histone 3 lysine trimethylation (H3K9me3) have been recently implicated in pHGGs' pathology, conferring to tumor heterogeneity. The present study investigates the potential involvement of H3K9me3 methyltransferase SETDB1 in the cellular function, progression, and clinical significance of pHGG. The bioinformatic analysis detected SETDB1 enrichment in pediatric gliomas compared to the normal brain, as well as positive and negative correlations with a proneural and mesenchymal signature, respectively. In our cohort of pHGGs, SETDB1 expression was significantly increased compared to pLGG and normal brain tissue and correlated with p53 expression, as well as reduced patients' survival. In accordance, H3K9me3 levels were also elevated in pHGG compared to the normal brain and were associated with worse patient survival. Gene silencing of SETDB1 in two patient-derived pHGG cell lines showed a significant reduction in cell viability followed by reduced cell proliferation and increased apoptosis. SETDB1 silencing further reduced cell migration of pHGG cells and the expression of the mesenchymal markers N-cadherin and vimentin. mRNA analysis of epithelial-mesenchymal transition (EMT) markers upon SETDB1 silencing showed a reduction in SNAI1 levels and downregulation of CDH2 along with the EMT regulator gene MARCKS. In addition, SETDB1 silencing significantly increased the bivalent tumor suppressor gene SLC17A7 mRNA levels in both cell lines, indicating its implication in the oncogenic process.Altogether, our findings demonstrate a predominant oncogenic role of SETDB1 in pHGG which along with elevated H3K9me3 levels correlate significantly to tumor progression and inferior patients' survival. There is evidence that targeting SETDB1 may effectively inhibit pHGG progression, providing a novel insight into the therapeutic strategies for pediatric gliomas. KEY MESSAGES: SETDB1 gene expression is enriched in pHGG compared to normal brain. SETDB1 expression is increased in pHGG tissues and associates with reduced patients' survival. Gene silencing of SETDB1 reduces cell viability and migration. SETDB1 silencing affects mesenchymal markers expression. SETDB1 silencing upregulates SLC17A7 levels. SETDB1 has an oncogenic role in pHGG.
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Glioma , Histonas , Humanos , Criança , Histonas/metabolismo , Histona Metiltransferases/metabolismo , Glioma/genética , Linhagem Celular , RNA Mensageiro , Histona-Lisina N-Metiltransferase/metabolismoRESUMO
OBJECTIVE: To investigate the retinal changes in choroideremia (CHM) patients to determine correlations between age, structure and function. SUBJECTS/METHODS: Twenty-six eyes from 13 male CHM patients were included in this prospective longitudinal study. Participants were divided into <50-year (n = 8) and ≥50-year (n = 5) old groups. Patients were seen at baseline, 6-month, and 1-year visits. Optical coherence tomography (OCT), OCT angiography, and fundus autofluorescence were performed to measure central foveal (CFT) and subfoveal choroidal thickness (SCT), as well as areas of preserved choriocapillaris (CC), ellipsoid zone (EZ), and autofluorescence (PAF). Patients also underwent functional investigations including visual acuity (VA), contrast sensitivity (CS), colour testing, microperimetry, dark adaptometry, and handheld electroretinogram (ERG). Vision-related quality-of-life was assessed by using the NEI-VFQ-25 questionnaire. RESULTS: Over the 1-year follow-up period, progressive loss was detected in SCT, EZ, CC, PAF, and CFT. Those ≥50-years exhibited more structural and functional defects with SCT, EZ, CC, and PAF showing strong correlation with patient age (rho ≤ -0.47, p ≤ 0.02). CS and VA did not change over the year, but CS was significantly correlated with age (rho = -0.63, p = 0.001). Delayed to unmeasurable dark adaptation, decreased colour discrimination and no detectable ERG activity were observed in all patients. Minimal functional deterioration was observed over one year with a general trend of slower progression in the ≥50-years group. CONCLUSIONS: Quantitative structural parameters including SCT, CC, EZ, and PAF are most useful for disease monitoring in CHM. Extended follow-up studies are required to determine longitudinal functional changes.
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Coroideremia , Corioide , Angiofluoresceinografia , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Tomografia de Coerência ÓpticaRESUMO
Choroideremia (CHM) is an X-linked recessive chorioretinal dystrophy caused by mutations in CHM, encoding for Rab escort protein 1 (REP1). Loss of functional REP1 leads to the accumulation of unprenylated Rab proteins and defective intracellular protein trafficking, the putative cause for photoreceptor, retinal pigment epithelium (RPE), and choroidal degeneration. CHM is ubiquitously expressed, but adequate prenylation is considered to be achieved, outside the retina, through the isoform REP2. Recently, the possibility of systemic features in CHM has been debated; therefore, in this study, whole metabolomic analysis of plasma samples from 25 CHM patients versus age- and sex-matched controls was performed. Results showed plasma alterations in oxidative stress-related metabolites, coupled with alterations in tryptophan metabolism, leading to significantly raised serotonin levels. Lipid metabolism was disrupted with decreased branched fatty acids and acylcarnitines, suggestive of dysfunctional lipid oxidation, as well as imbalances of several sphingolipids and glycerophospholipids. Targeted lipidomics of the chmru848 zebrafish provided further evidence for dysfunction, with the use of fenofibrate over simvastatin circumventing the prenylation pathway to improve the lipid profile and increase survival. This study provides strong evidence for systemic manifestations of CHM and proposes potentially novel pathomechanisms and targets for therapeutic consideration.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Coroideremia/metabolismo , Metabolismo dos Lipídeos/genética , Estresse Oxidativo/genética , Proteínas de Peixe-Zebra/genética , Adulto , Animais , Estudos de Casos e Controles , Coroideremia/genética , Fenofibrato/farmacologia , Glicerofosfolipídeos/metabolismo , Humanos , Hipolipemiantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipidômica , Masculino , Metabolômica , Pessoa de Meia-Idade , Prenilação , Serotonina/metabolismo , Sinvastatina/farmacologia , Esfingolipídeos/metabolismo , Triptofano/metabolismo , Adulto Jovem , Peixe-ZebraRESUMO
Alterations in global histone methylation regulate gene expression and participate in cancer onset and progression. The profile of histone methylation marks in pediatric astrocytomas is currently understudied with limited data on their distribution among grades. The global expression patterns of repressive histone marks H3K9me3, H3K27me3, and H4K20me3 and active H3K4me3 and H3K36me3 along with their writers SUV39H1, SETDB1, EZH2, MLL2, and SETD2 were investigated in 46 pediatric astrocytomas and normal brain tissues. Associations between histone marks and modifying enzymes with clinicopathological characteristics and disease-specific survival were studied along with their functional impact in proliferation and migration of pediatric astrocytoma cell lines using selective inhibitors in vitro. Upregulation of histone methyltransferase gene expression and deregulation of histone code were detected in astrocytomas compared to normal brain tissues, with higher levels of SUV39H1, SETDB1, and SETD2 as well as H4K20me3 and H3K4me3 histone marks. Pilocytic astrocytomas exhibited lower MLL2 levels compared to diffusely infiltrating tumors indicating a differential pattern of epigenetic regulator expression between the two types of astrocytic neoplasms. Moreover, higher H3K9me3, H3K36me3, and SETDB1 expression was detected in grade IIΙ/IV compared to grade II astrocytomas. In univariate analysis, elevated H3K9me3 and MLL2 and diminished SUV39H1 expression adversely affected survival. Upon multivariate survival analysis, only SUV39H1 expression was revealed as an independent prognostic factor of adverse significance. Treatment of pediatric astrocytoma cell lines with SUV39H1 inhibitor reduced proliferation and cell migration. Our data implicate H3K9me3 and SUV39H1 in the pathobiology of pediatric astrocytomas, with SUV39H1 yielding prognostic information independent of other clinicopathologic variables.
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Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Perfilação da Expressão Gênica , Código das Histonas/fisiologia , Histona-Lisina N-Metiltransferase/biossíntese , Metiltransferases/biossíntese , Proteínas Repressoras/biossíntese , Adolescente , Astrocitoma/diagnóstico , Astrocitoma/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica/métodos , Histona-Lisina N-Metiltransferase/genética , Humanos , Lactente , Masculino , Metilação , Metiltransferases/genética , Prognóstico , Proteínas Repressoras/genéticaRESUMO
AIMS: Using optical coherence tomography angiography (OCTA) to characterise microvascular changes in the retinal plexuses and choriocapillaris (CC) of patients with MYO7A and USH2A mutations and correlate with genotype, retinal structure and function. METHODS: Twenty-seven patients with molecularly confirmed USH2A (n=21) and MYO7A (n=6) mutations underwent macular 6×6 mm OCTA using the AngioVue. Heidelberg spectral-domain OCT scans and MAIA microperimetry were also performed, the preserved ellipsoid zone (EZ) band width and mean macular sensitivity (MS) were recorded. OCTA of the inner retina, superficial capillary plexus (SCP), deep capillary plexus (DCP) and CC were analysed. Vessel density (VD) was calculated from the en face OCT angiograms of retinal circulation. RESULTS: Forty-eight eyes with either USH2A (n=37, mean age: 34.4±12.2 years) or MYO7A (n=11, mean age: 37.1±12.4 years), and 35 eyes from 18 age-matched healthy participants were included. VD was significantly decreased in the retinal circulation of patients with USH2A and MYO7A mutations compared with controls (p<0.001). Changes were observed in both the SCP and DCP, but no differences in retinal perfusion were detected between USH2A and MYO7A groups. No vascular defects were detected in CC of the USH2A group, but peripheral defects were detected in older MYO7A patients from the fourth decade of life. VD in the DCP showed strong association with MS and EZ width (Spearman's rho =0.64 and 0.59, respectively, p<0.001). CONCLUSION: OCTA was able to detect similar retinal microvascular changes in patients with USH2A and MYO7A mutations. The CC was generally affected in MYO7A mutations. OCT angiography may further enhance our understanding of inherited eye diseases and their phenotype-genotype associations.
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Proteínas da Matriz Extracelular/genética , Mutação , Miosina VIIa/genética , Doenças Retinianas/diagnóstico , Vasos Retinianos/patologia , Síndromes de Usher/patologia , Adulto , Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/genética , Doenças Retinianas/fisiopatologia , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica , Síndromes de Usher/diagnóstico por imagem , Síndromes de Usher/genética , Acuidade Visual/fisiologia , Testes de Campo Visual , Adulto JovemRESUMO
INTRODUCTION: Torkildsen operation is a ventriculo-cisternal shunt that diverts the cerebrospinal fluid flow from one of the lateral ventricles, via a ventricular catheter, to the cisterna magna of the posterior fossa. It is the first described operation of CSF diversion for the treatment of hydrocephalus [1] (Scarff, 1963). PRESENTATION OF CASE: We present the case of a premature infant who presented with post hemorrhagic hydrocephalus who underwent several failed CSF diversion surgeries before Torkildsen shunt procedure. The patient overcame the irregularities of CSF circulation that were observed before the operation and his post-operative course was uneventful, in terms of CSF -related complications. DISCUSSION: We summarize the historical data and the technical aspects of the procedure, and we present a brief literature review of the indications and limitations associated with it. CONCLUSION: Torkildsen shunt can be effective in selected patients with hydrocephalus even in the modern era of computed tomography and magnetic resonance imaging. the procedure enables one to avoid a standard ventriculoperitoneal shunt, especially in cases it is not technically feasible.
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Fibrous dysplasia is a rare non-malignant condition where fibrous tissue replaces the normal bone architecture. Involvement of temporal and occipital bones is exceptionally rare and is associated with unique complications. A 10-year-old boy presented with right retroauricular enlargement and pain. Imaging studies and biopsy revealed fibrous dysplasia of the temporal and occipital bones. There was no hearing loss or sequelae arising from posterior fossa compression. The patient was discharged with follow-up instructions. Only 10 cases of occipital bone fibrous dysplasia have been reported in the medical literature. Occipital bone fibrous dysplasia can be complicated with Chiari malformation and syringomyelia while temporal bone involvement is associated with hearing loss. These potential developments require close follow-up that includes detailed neurologic examination, imaging and audiology.
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Choroideremia is an X-linked inherited chorioretinal dystrophy leading to blindness by late adulthood. Choroideremia is caused by mutations in the CHM gene which encodes Rab escort protein 1 (REP1), an ubiquitously expressed protein involved in intracellular trafficking and prenylation activity. The exact site of pathogenesis remains unclear but results in degeneration of the photoreceptors, retinal pigment epithelium and choroid. Animal and stem cell models have been used to study the molecular defects in choroideremia and test effectiveness of treatment interventions. Natural history studies of choroideremia have provided additional insight into the clinical phenotype of the condition and prepared the way for clinical trials aiming to investigate the safety and efficacy of suitable therapies. In this review, we provide a summary of the current knowledge on the genetics, pathophysiology, clinical features and therapeutic strategies that might become available for choroideremia in the future, including gene therapy, stem cell treatment and small-molecule drugs with nonsense suppression action.
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BACKGROUND: Pediatric nonmissile penetrating head injury (NMPHI) is usually accidental attributed mainly to the softer skulls of growing children. However, it is a rare entity, and therefore no consensus exists regarding treatment to effectively prevent immediate and long-term complications. Throughout the literature, these injuries are mostly discussed in case reviews and case series in the general population. No data originating from randomized studies are available because of ethical and practical limitations. METHODS: We retrospectively studied and present 5 cases of children with NMPHI treated in the last 6 years in the Neurosurgery Department of Children's Hospital "Aghia Sofia". We performed a review of the literature in PubMed, using the key words "non-missile," "penetrating head injury," and "pediatric." We included case reports and case series involving pediatric cases since 2008 and selected older reports as well as certain literature reviews focusing on analysis of complications and treatment suggestions. We compared reported practice in various institutions with suggestions from the literature. RESULTS: In the last year, 4 literature reviews were published suggesting treatment algorithms of NMPHIs. Surgery timing and method as well as anticonvulsant and antibiotic therapy still remain debatable. The only review concentrating on pediatric populations dates back to 1994, based on patient outcome studies from the 1980s. In our review, treatment steps were similar among various institutions and resembled recently suggested algorithms, with better treatment outcomes than originally reported 30 years ago.
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Corpos Estranhos/cirurgia , Traumatismos Cranianos Penetrantes/epidemiologia , Traumatismos Cranianos Penetrantes/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Escala de Coma de Glasgow , Traumatismos Cranianos Penetrantes/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos RetrospectivosRESUMO
Synovial sarcoma (SS) most commonly affects the lower limbs of males in the third to fifth decades of life, with masses of the head and neck accounting for 3-10% of all cases, mainly as a metastatic lesion. The lack of specific symptoms and radiological features in addition to the diversity of their microscopic aspects may cause confusion in the diagnosis; hence, knowledge of the unusual locations of SSs is very important. The immunohistochemistry, and more recently the cytogenetic studies, contribute to the differential diagnosis. We report the case of a 12-year-old girl with a rare primary SS in the suboccipital region, which underwent complete surgical resection.
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Background: Aplasia cutis congenita (ACC) is a part of a heterogeneous group of conditions characterized by the congenital absence of epidermis, dermis, and in some cases, subcutaneous tissues or bone usually involving the scalp vertex. There is an estimated incidence of 3 in 10,000 births resulting in a total number of 500 reported cases to date. The lesions may occur on every body surface although localized scalp lesions form the most frequent pattern (70%). Complete aplasia involving bone defects occurs in approximately 20% of cases. ACC can occur as an isolated defect or can be associated with a number of other congenital anomalies such as limb anomalies or embryologic malformations. In patients with large scalp and skull defects, there is increased risk of infection and bleeding along with increased mortality and therefore prompt and effective management is advised. Case Description: We describe two cases of ACC, involving a 4 × 3 cm defect managed conservatively and a larger 10 × 5 cm defect managed surgically with the use of a temporo-occipital scalp flap. Both cases had an excellent outcome. Conclusions: Multiple treatment regimens exist for ACC, but there is no consensus on treatment strategies. Conservative treatment has been described and advocated, but many authors have emphasized the disadvantages of this treatment modality. Decision between conservative and surgical management must be individualized according to lesion size and location.
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Herpes simplex virus Type 1 (HSV-1) is a human neurotropic virus causing encephalitis, corneal blindness or several peripheral nervous system disorders. Herpes Simplex encephalitis (HSE) is the most devastating clinical syndrome with severe morbidity and mortality. Hydrocephalus associated with viral meningoencephalitis is an extremely rare entity with only few documented cases, predominantly due to HSV-2 infection. HSV-1 infection of central nervous system present in the majority of the cases as encephalitis. We report a rare case of an 11-year-old child suffering from HSV-1 infection of central nervous system causing hydrocephalus without evidence of encephalitis.
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Hereditary hemorrhagic telangiectasia is a rare autosomal dominant inherited disease that is usually complicated by visceral vascular malformations. Patients harboring such malformations are at increased risk of brain abscess formation, which despite advances in diagnostic and surgical methods remains a life threatening medical emergency with high mortality and morbidity rates. In the present report we describe a case of cerebral abscess due to silent pulmonary arteriovenous malformation (AVM) in a young patient previously undiagnosed for hereditary hemorrhagic telangiectasia syndrome (HHT).