RESUMO
OBJECTIVES: Recently, it was noted that fetuses with open spina bifida (OSB) may have a midline cystic structure evident on ultrasound. Our aims were to determine the prevalence of this cystic structure, shed light on its pathophysiology and investigate the association between its presence and other characteristic brain findings in fetuses with OSB. METHODS: This was a single-center retrospective study of all fetuses with OSB and available cineloop images in the axial plane referred to the Ontario Fetal Centre, Toronto, Canada, between June 2017 and May 2022. Ultrasound and magnetic resonance imaging (MRI) data obtained between 18 + 0 and 25 + 6 weeks were reviewed in search of a midline cystic structure. Pregnancy and lesion characteristics were collected. Transcerebellar diameter (TCD), clivus-supraocciput angle (CSA) and additional brain abnormalities (abnormal cavum septi pellucidi (CSP), abnormal corpus callosum (CC) and periventricular nodular heterotopia (PNH)) were assessed. In cases of in-utero repair, imaging findings were reviewed postoperatively. In cases of termination, neuropathological findings were reviewed, if available. RESULTS: Of 76 fetuses with OSB, 56 (73.7%) had a suprapineal cystic structure on ultrasound. The percentage of agreement between ultrasound and MRI detection was 91.5% (Cohen's kappa coefficient, 0.78 (95% CI, 0.57-0.98)). Brain autopsy in terminated cases revealed a dilatation of the posterior third ventricle, with redundant tela choroidea and arachnoid forming the membranous roof of the third ventricle, anterior and superior to the pineal gland. A cyst wall could not be identified, indicating that the structure was a pseudocyst. The presence of the pseudocyst was associated with a smaller CSA (pseudocyst absent, 62.11 ± 9.60° vs pseudocyst present, 52.71 ± 8.22°; P = 0.04). When the pseudocyst was present, its area was correlated inversely with TCD (r, -0.28 (95% CI, -0.51 to -0.02); P = 0.04). Fetal surgery did not have any impact on the growth rate of the pseudocyst (fetal surgery, 5.07 ± 3.29 mm2 /week vs expectant management, 4.35 ± 3.17 mm2 /week; P = 0.58). The presence of the pseudocyst was not associated with abnormal CSP, CC or presence of PNH. None of the cases with available postnatal follow-up required surgical procedure related to the pseudocyst. CONCLUSIONS: Approximately 75% of all OSB cases have a suprapineal pseudocyst. Its presence is associated with the degree of hindbrain herniation but not with abnormalities of the CSP and CC or presence of PNH. Thus, it should not be regarded as additional brain pathology and should not preclude fetuses from undergoing fetal surgery for OSB. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Espinha Bífida Cística , Gravidez , Feminino , Humanos , Espinha Bífida Cística/diagnóstico por imagem , Estudos Retrospectivos , Idade Gestacional , Encéfalo/diagnóstico por imagem , Feto , Ultrassonografia Pré-Natal/métodosRESUMO
Quantum cascade detectors (QCDs) are devices operating at zero external bias with a low dark-current. They show linear detection and high saturation intensities, making them suitable candidates for heterodyne detection in long-wave infrared (LWIR) free space optical communication systems. We present an approach to mitigate the performance limitation at long wavelengths, by a comparison of similar single and multi-period QCDs for optimizing their responsivity and noise behaviour. Our InGaAs/InAlAs/InP ridge QCDs are designed for operation at λ = 9.124 µm. Optical waveguide simulations support the accurate optical characterization. A detailed device analysis reveals room-temperature responsivities of 111 mA/W for the 15-period and 411 mA/W for the single-period device.
RESUMO
OBJECTIVE: Monochorionic twin pregnancies are at increased risk of single intrauterine death (sIUD) and subsequent brain injury in the surviving twin owing to shared placentation. We assessed the association between middle cerebral artery peak systolic velocity (MCA-PSV) and cerebral injury on magnetic resonance imaging (MRI) and examined the association between cerebral findings on diffusion-weighted imaging (DWI) and those on T2-weighted imaging following spontaneous sIUD. METHODS: This was a retrospective cohort study of monochorionic pregnancies complicated by spontaneous sIUD followed at a tertiary center between January 2008 and January 2020. Pregnancies with sIUD following laser treatment, those with selective feticide, double IUD occurring on the same day or sIUD before 14 weeks' gestation were excluded, as were cases in which MCA-PSV was not measured or DWI-MRI was not performed. The ability of MCA-PSV Doppler to predict subsequent cerebral injury on MRI was assessed, and DWI findings were analyzed and compared with those on susceptibility-weighted imaging (SWI) and T2-weighted MRI to determine its diagnostic accuracy. RESULTS: We assessed 64 monochorionic pregnancies complicated by spontaneous sIUD. Of these, 47 (73.4%) pregnancies underwent fetal brain MRI and met the inclusion criteria. Sixteen (34.0%) of these fetuses demonstrated cerebral injury on MRI. The median interval between the diagnosis of sIUD and MRI examination was 5 days. Fetuses with increased MCA-PSV > 1.5 multiples of the median (MoM) following sIUD were significantly more likely to demonstrate cerebral injury on MRI than were those with normal MCA-PSV (68.8% vs 38.7%; P = 0.05). The sensitivity and specificity of MCA-PSV > 1.5 MoM for predicting cerebral injury on MRI were 68.8% (95% CI, 41.3-88.9%) and 61.3% (95% CI, 42.2-78.2%), respectively. Patterns of early cerebral injury on T2-weighted and SWI-MRI included acute or subacute tissue swelling (n = 6), parenchymal atrophy (n = 7), loss of cortical ribbon (n = 1) and hemorrhage (n = 8). Early MRI within approximately 2 weeks after the diagnosis of sIUD demonstrated abnormal DWI along with coexisting SWI and T2-weighted sequelae in 56.3% (9/16) of cases. When DWI was normal and a second MRI examination was performed later (n = 7), there were no ischemic changes evident on T2-weighted imaging. CONCLUSIONS: Increased MCA-PSV is associated with, but predicts poorly, cerebral injury after sIUD. Early MRI with DWI within approximately 2 weeks after the diagnosis of sIUD is valuable in identifying any cerebral injury. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Lesões Encefálicas , Gravidez de Gêmeos , Velocidade do Fluxo Sanguíneo , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/etiologia , Feminino , Feto , Humanos , Artéria Cerebral Média/diagnóstico por imagem , Gravidez , Estudos Retrospectivos , Ultrassonografia Pré-NatalRESUMO
A new method combining online nano solid phase extraction coupled with Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was developed to extract and analyze organic matter (OM) from microliter volumes of salt containing soil solution samples. This approach allows the reproducible analysis of only minute amounts of organic carbon (down to 10 ng C) without the need of further sample preparation. The new method was applied to unravel developing small-scale patterns of dissolved organic matter (DOM) in soil solutions of a soil column experiment in which Zea mays plants were grown for 3 weeks. Soil solution was sampled by micro suction cups from the undisturbed soil-root system once a week. Growth of the root system and, hence, position of individual roots relative to the suction cups was followed by X-ray computed tomography (X-ray CT). Our method makes it possible to resolve the chemical complexity of soil solution OM (up to 4300 molecular formulas from 2.5 µL sample). This allows to observe chemical gradients in the rhizosphere on a molecular level over time. The increasing influence of roots on soil solution OM is visible from higher molecular masses, an increasing degree of oxygenation and a higher fraction of formulas containing heteroatoms. The online nano solid phase extraction-FT-ICR-MS method provides novel insight into the processes affecting DOM in the rhizosphere, such as root exudation, microbial processes, and soil organic matter stabilization.
Assuntos
Ciclotrons , Análise de Fourier , Espectrometria de Massas/métodos , Rizosfera , Solo/química , Extração em Fase Sólida/métodos , Nanotecnologia , Raízes de Plantas , Zea maysRESUMO
OBJECTIVES: Septo-optic dysplasia (SOD) is a clinical syndrome characterized by varying combinations of optic nerve hypoplasia, pituitary gland hypoplasia and abnormal cavum septi pellucidi. It is suspected on prenatal imaging when there is non-visualization or hypoplasia of the septal leaflets. Long-term postnatal outcomes of fetuses with prenatally suspected SOD have been documented poorly. The aims of this study were to describe the natural history of deficient septal leaflets, to quantify the incidence of postnatally confirmed SOD and to document the visual, endocrine and long-term neurodevelopmental outcomes of these infants. METHODS: This was an observational retrospective study of all fetuses with prenatal imaging showing isolated septal agenesis, assessed at a single tertiary center over an 11-year period. Pregnancy, delivery and neonatal outcomes and pre- and postnatal imaging findings were reviewed. Neonatal evaluations or fetal autopsy reports were assessed for confirmation of SOD. Ophthalmologic, endocrine, genetic and long-term developmental evaluations were assessed. Imaging findings and outcome were compared between infants with and those without postnatally confirmed SOD. RESULTS: Of 214 fetuses presenting with septal absence on prenatal ultrasound and magnetic resonance imaging (MRI), 18 (8.4%) were classified as having suspected isolated septal agenesis suspicious for SOD. Uniform prenatal MRI findings in cases with suspected SOD included remnants of the leaflets of the cavum septi pellucidi, fused forniceal columns, normal olfactory bulbs and tracts and a normal optic chiasm. Twelve fetuses were liveborn and five (27.8%) had postnatally confirmed SOD. Only two of these five fetuses had additional prenatal imaging features (pituitary cyst, microphthalmia and optic nerve hypoplasia) supporting a diagnosis of SOD. The other three confirmed SOD cases had no predictive prenatal or postnatal imaging findings that reliably differentiated them from cases without confirmed SOD. Visual and endocrine impairments were present in two (40%) and four (80%) cases with confirmed SOD, respectively. In those with visual and/or endocrine impairment, developmental delay (median age at follow-up, 2.5 (interquartile range, 2.5-7.0) years) was common (80%) and mostly severe. Neonates with isolated septal agenesis and a lack of visual or endocrine abnormalities to confirm SOD had normal development. CONCLUSIONS: Only a quarter of fetuses with isolated septal agenesis suggestive of SOD will have postnatal confirmation of the diagnosis. Clinical manifestations of SOD are variable, but neurodevelopmental delay may be more prevalent than thought formerly. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Displasia Septo-Óptica/epidemiologia , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Ontário/epidemiologia , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Displasia Septo-Óptica/diagnóstico por imagem , Septo Pelúcido/anormalidades , Ultrassonografia Pré-NatalRESUMO
Post-translational protein modifications exponentially expand the functional complement of proteins encoded by the human genome. One such modification is the covalent addition of a methyl group to arginine or lysine residues, which is used to regulate a substantial proportion of the proteome. Arginine and lysine methylation are catalyzed by protein arginine methyltransferase (PRMTs) and protein lysine methyltransferase proteins (PKMTs), respectively; each methyltransferase has a specific set of target substrates. Here, we report a male with severe intellectual disability, facial dysmorphism, microcephaly, short stature, brachydactyly, cryptorchidism and seizures who was found to have a homozygous 15,309 bp deletion encompassing the transcription start site of PRMT7, which we confirmed is functionally a null allele. We show that the patient's cells have decreased levels of protein arginine methylation, and that affected proteins include the essential histones, H2B and H4. Finally, we demonstrate that patient cells have altered Wnt signaling, which may have contributed to the skeletal abnormalities. Our findings confirm the recent disease association of PRMT7, expand the phenotypic manifestations of this disorder and provide insight into the molecular pathogenesis of this new condition.
Assuntos
Braquidactilia/genética , Deficiência Intelectual/genética , Microcefalia/genética , Proteína-Arginina N-Metiltransferases/genética , Anormalidades Múltiplas/genética , Arginina/metabolismo , Pré-Escolar , Cromossomos Humanos Par 16 , Face/anormalidades , Feminino , Dedos/anormalidades , Deleção de Genes , Humanos , Lactente , Recém-Nascido , Masculino , Sítio de Iniciação de Transcrição , Via de Sinalização Wnt/genéticaRESUMO
INTRODUCTION: Postpartum haemorrhage (PPH) is one of the most threatening and unpredictable emergencies in obstetrics. Worldwide it is a leading cause of maternal death. The outcome significantly depends on competent management by a skilled interdisciplinary team. For health professionals, PPH might cause stress, anxiety and inability to act adequately. It is estimated that 70-80% of maternal deaths related to PPH are due to preventable management errors. This leads to the conclusion that health professionals need training in order to competently manage a PPH emergency. The aim of this study is to summarise the evidence on the effectiveness of different training methods to support the professional and competent management of PPH. MATERIAL AND METHODS: A systematic literature review was conducted. The search was performed on the data bases Cochrane Library, Embase, Medline, CINAHL complete and MIDIRS and was supplemented by hand searching. The selected studies were analysed and checked for content and quality based on specific criteria. RESULTS: The 11 included studies support the effectiveness of simulation training. The subjective indicators «self-confidence¼, «knowledge¼, «competence¼ «stress levels¼, «team work¼ and «communication¼ could be improved, as well as the objective indicators «team performance¼ and «knowledge¼. 3 studies could establish a sustainable effect of the simulation training 6 weeks, 3 months and 6 months, respectively, after the training session. However, in all included studies this effect was not tested in a clinical context. Therefore the clinical effectiveness of simulation-based training on clinical outcome is unknown. 2 studies indicate a benefit of simulation-based training versus the lecture and discussion-based method. In addition, no evidence exists as to whether the effectiveness of simulation-based training depends on high fidelity circumstances such as the location at which training is taking place (simulation centre vs. local obstetrics room) or whether it could be influenced by teamwork training. DISCUSSION AND CONCLUSION: It is recommended to offer an interdisciplinary training on a regular basis even after accomplished graduation training of professionals in the field of obstetrics. No recommendations can be made concerning the type and frequency of training. There is an urgent need for more evidence related to the effectiveness of different training methods for adequate PPH management.
Assuntos
Competência Clínica , Currículo , Avaliação Educacional , Obstetrícia/educação , Hemorragia Pós-Parto/diagnóstico , Hemorragia Pós-Parto/terapia , Ensino , Feminino , Alemanha , Treinamento com Simulação de Alta Fidelidade/métodos , Humanos , GravidezRESUMO
Intermittent scanning for continuous-wave quantum cascade lasers is proposed along with a custom-built laser driver optimized for such operation. This approach lowers the overall heat dissipation of the laser by dropping its drive current to zero between individual scans and holding a longer pause between scans. This allows packaging cw-QCLs in TO3 housings with built-in collimating optics, thus reducing cost and footprint of the device. The fully integrated, largely analog, yet flexible laser driver eliminates the need for any external electronics for current modulation, lowers the demands on power supply performance, and allows shaping of the tuning current in a wide range. Optimized ramp shape selection leads to large and nearly linear frequency tuning (>1.5 cm−1). Experimental characterization of the proposed scheme with a QCL emitting at 7.7 µm gave a frequency stability of 3.2×10−5 cm−1 for the laser emission, while a temperature dependence of 2.3×10−4 cm−1/K was observed when the driver electronics was exposed to sudden temperature changes. We show that these characteristics make the driver suitable for high precision trace gas measurements by analyzing methane absorption lines in the respective spectral region.
RESUMO
Biotinidase deficiency is an autosomal recessive condition caused by pathogenic variants in the BTD gene. Resultant deficiency of free biotin leads to impaired activity of the enzyme carboxylase and related neurologic, dermatologic, and ocular symptoms. Many of these are reversible on treatment, but early recognition and commencement of biotin supplementation are critical. This practice is especially important in countries where routine neonatal screening for biotinidase deficiency is not performed. In this report comprising 14 patients from multiple centers, we demonstrate the MR imaging patterns of this disorder at various age groups. Knowledge of these patterns in the appropriate clinical context will help guide early diagnosis of this treatable metabolic disorder.
Assuntos
Deficiência de Biotinidase , Recém-Nascido , Humanos , Deficiência de Biotinidase/diagnóstico por imagem , Deficiência de Biotinidase/tratamento farmacológico , Biotina/metabolismo , Biotina/uso terapêutico , Biotinidase/genética , Biotinidase/metabolismo , Biotinidase/uso terapêutico , Triagem Neonatal , NeuroimagemRESUMO
AIM: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is known as a relatively mild leukoencephalopathy. We investigated the occurrence of severe variants of LBSL with extensive brain magnetic resonance imaging (MRI) abnormalities. METHOD: MRIs of approximately 3,000 patients with an unknown leukoencephalopathy were retrospectively reviewed for extensive signal abnormalities of the cerebral and cerebellar white matter, posterior limb of the internal capsule, cerebellar peduncles, pyramids, and medial lemniscus. Clinical data were retrospectively collected. RESULTS: Eleven patients fulfilled the MRI criteria (six males); six had DARS2 mutations. Clinical and laboratory findings did not distinguish between patients with and without DARS2 mutations, but MRI did. Patients with DARS2 mutations more often had involvement of structures typically affected in LBSL, including decussatio of the medial lemniscus, anterior spinocerebellar tracts, and superior and inferior cerebellar peduncles. Also, involvement of the globus pallidus was associated with DARS2 mutations. Earliest disease onset was neonatal; earliest death at 20 months. INTERPRETATION: This study confirms the occurrence of early infantile, severe LBSL, extending the known phenotypic range of LBSL. Abnormality of specific brainstem tracts and cerebellar peduncles are MRI findings that point to the correct diagnosis.
Assuntos
Encéfalo/patologia , Leucoencefalopatias/patologia , Doenças Mitocondriais/patologia , Fibras Nervosas Mielinizadas/patologia , Aspartato-tRNA Ligase/deficiência , Aspartato-tRNA Ligase/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucoencefalopatias/genética , Imageamento por Ressonância Magnética , Masculino , Doenças Mitocondriais/genética , Mutação , Estudos Retrospectivos , Índice de Gravidade de Doença , Medula Espinal/patologiaRESUMO
BACKGROUND: Compared with ultrasound, magnetic resonance imaging (MRI) offers superior visualization ofthe fetal brain. It confirms and characterizes brain abnormalities detected by prenatal ultrasound, particularly in late pregnancy when acoustic windows are difficult or fetal position is inaccessible. Prior to July 2008, only two studies were attempted at our institution as local technical expertise was unavailable. Following collaboration with a neuroradiologist at an expert centre, images ofsufficient quality for diagnosis were obtained. OBJECTIVE: The study objective is to evaluate the initial experience with fetal brain MRI and its effects on patient counselling and management in a resource limited healthcare system. METHOD: In seven fetuses with abnormal ultrasound neuroimaging, fetal MRI was performed with T2-weighted single-shot fast spin-echo (SSFSE) sequences using a 1.5T magnet (GE Medical Systems, Milwaukee, WI). RESULTS: Magnetic resonance imaging did not alter ultrasound diagnosis in two patients (28%); however it changed the diagnosis in three (43%), provided additional information in one (14%) and changed management in two (28%) patients. CONCLUSION: Magnetic resonance imaging availability further elucidated brain pathology, aided patient counselling, parental decision-making and multidisciplinary management.
Assuntos
Encefalopatias/diagnóstico , Doenças Fetais/diagnóstico , Imageamento por Ressonância Magnética , Malformações do Sistema Nervoso/diagnóstico , Adulto , Feminino , Humanos , Jamaica , Gravidez , Ultrassonografia Pré-Natal , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Patients with neurofibromatosis 1 are at increased risk of developing brain tumors, and differentiation from contrast-enhancing foci of abnormal signal intensity can be challenging. We aimed to longitudinally characterize rare, enhancing foci of abnormal signal intensity based on location and demographics. MATERIALS AND METHODS: A total of 109 MR imaging datasets from 19 consecutive patients (7 male; mean age, 8.6 years; range, 2.3-16.8 years) with neurofibromatosis 1 and a total of 23 contrast-enhancing parenchymal lesions initially classified as foci of abnormal signal intensity were included. The mean follow-up period was 6.5 years (range, 1-13.8 years). Enhancing foci of abnormal signal intensity were followed up with respect to presence, location, and volume. Linear regression analysis was performed. RESULTS: Location, mean peak volume, and decrease in enhancing volume over time of the 23 lesions were as follows: 10 splenium of the corpus callosum (295 mm3, 5 decreasing, 3 completely resolving, 2 surgical intervention for change in imaging appearance later confirmed to be gangliocytoma and astrocytoma WHO II), 1 body of the corpus callosum (44 mm3, decreasing), 2 frontal lobe white matter (32 mm3, 1 completely resolving), 3 globus pallidus (50 mm3, all completely resolving), 6 cerebellum (206 mm3, 3 decreasing, 1 completely resolving), and 1 midbrain (34 mm3). On average, splenium lesions began to decrease in size at 12.2 years, posterior fossa lesions at 17.1 years, and other locations at 9.4 years of age. CONCLUSIONS: Albeit very rare, contrast-enhancing lesions in patients with neurofibromatosis 1 may regress over time. Follow-up MR imaging aids in ascertaining regression. The development of atypical features should prompt further evaluation for underlying tumors.
Assuntos
Neurofibromatose 1 , Adolescente , Neoplasias Encefálicas/diagnóstico por imagem , Criança , Pré-Escolar , Corpo Caloso , Feminino , Globo Pálido , Humanos , Imageamento por Ressonância Magnética , Masculino , Neurofibromatose 1/diagnóstico por imagemRESUMO
BACKGROUND AND PURPOSE: Achieving a specific diagnosis in leukodystrophies is often difficult due to clinical and genetic heterogeneity. Mitochondrial defects cause 5%-10% of leukodystrophies. Our objective was to define MR imaging features commonly shared by mitochondrial leukodystrophies and to distinguish MR imaging patterns related to specific genetic defects. MATERIALS AND METHODS: One hundred thirty-two patients with a mitochondrial leukodystrophy with known genetic defects were identified in the data base of the Amsterdam Leukodystrophy Center. Numerous anatomic structures were systematically assessed on brain MR imaging. Additionally, lesion characteristics were scored. Statistical group analysis was performed for 57 MR imaging features by hierarchic testing on clustered genetic subgroups. RESULTS: MR imaging features indicative of mitochondrial disease that were frequently found included white matter rarefaction (n = 50 patients), well-delineated cysts (n = 20 patients), T2 hyperintensity of the middle blade of the corpus callosum (n = 85 patients), and symmetric abnormalities in deep gray matter structures (n = 42 patients). Several disorders or clusters of disorders had characteristic features. The combination of T2 hyperintensity in the brain stem, middle cerebellar peduncles, and thalami was associated with complex 2 deficiency. Predominantly periventricular localization of T2 hyperintensities and cystic lesions with a distinct border was associated with defects in complexes 3 and 4. T2-hyperintense signal of the cerebellar cortex was specifically associated with variants in the gene NUBPL. T2 hyperintensities predominantly affecting the directly subcortical cerebral white matter, globus pallidus, and substantia nigra were associated with Kearns-Sayre syndrome. CONCLUSIONS: In a large group of patients with a mitochondrial leukodystrophy, general MR imaging features suggestive of mitochondrial disease were found. Additionally, we identified several MR imaging patterns correlating with specific genotypes. Recognition of these patterns facilitates the diagnosis in future patients.
Assuntos
Encéfalo , Transtornos Leucocíticos , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Tronco Encefálico , Humanos , Transtornos Leucocíticos/diagnóstico por imagem , Leucócitos , Mitocôndrias , Proteínas Mitocondriais , Estudos Retrospectivos , Substância Branca/diagnóstico por imagemRESUMO
BACKGROUND AND PURPOSE: Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama congenital muscular dystrophy are α-dystroglycan-related muscular disorders associated with brain malformations and eye abnormalities in which no structural inner ear abnormality has been described radiologically. We collected patients from 6 tertiary pediatric hospitals and reported the radiologic features and frequency of inner ear dysplasias. MATERIALS AND METHODS: Patients previously diagnosed clinicoradiologically with Walker-Warburg syndrome, muscle-eye-brain disease, or Fukuyama congenital muscular dystrophy were included. We recorded the pathogenic variant, when available. Brain MR imaging and/or CT findings were reviewed in consensus, and inner ear anomalies were classified according to previous description in the literature. We then correlated the clinicoradiologic phenotype with the inner ear phenotype. RESULTS: Thirteen patients fulfilled the criteria for the Walker-Warburg syndrome phenotype, 8 for muscle-eye-brain disease, and 3 for Fukuyama congenital muscular dystrophy. A dysplastic cochlea was demonstrated in 17/24. The most frequent finding was a pronounced cochlear hypoplasia type 4 with a very small anteriorly offset turn beyond the normal-appearing basal turn (12/13 patients with Walker-Warburg syndrome and 1/11 with muscle-eye-brain disease or Fukuyama congenital muscular dystophy). Two of 8 patients with muscle-eye-brain disease, 1/3 with Fukuyama congenital muscular dystrophy, and 1/13 with Walker-Warburg syndrome showed a less severe cochlear hypoplasia type 4. The remaining patients without Walker-Warburg syndrome were healthy. The vestibule and lateral semicircular canals of all patients were normal. Cranial nerve VIII was present in all patients with diagnostic MR imaging. CONCLUSIONS: Most patients with the severe α-dystroglycanopathy Walker-Warburg syndrome phenotype have a highly characteristic cochlear hypoplasia type 4. Patients with the milder variants, muscle-eye-brain disease and Fukuyama congenital muscular dystrophy, more frequently have a normal cochlea or milder forms of hypoplasia.
Assuntos
Cóclea/anormalidades , Síndrome de Walker-Warburg/patologia , Adolescente , Criança , Pré-Escolar , Distroglicanas/genética , Feminino , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética/métodos , Masculino , Neuroimagem , Fenótipo , Síndrome de Walker-Warburg/complicações , Síndrome de Walker-Warburg/genética , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Neuronal ceroid lipofuscinoses are a group of neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigments in neuronal cells. As a result of storage material in the brain and retina, clinical manifestations include speech delay, cognitive dysfunction, motor regression, epilepsy, vision loss, and early death. At present, 14 different ceroid lipofuscinosis (CLN) genes are known. Recently, the FDA approved the use of recombinant human proenzyme of tripeptidyl-peptidase 1 for CLN2 disease, while phase I/IIa clinical trials for gene therapy in CLN3 and CLN6 are ongoing. Early diagnosis is, therefore, key to initiating treatment and arresting disease progression. Neuroimaging features of CLN1, CLN2, CLN3, and CLN5 diseases are well-described, with sparse literature on other subtypes. We aimed to investigate and expand the MR imaging features of genetically proved neuronal ceroid lipofuscinoses subtypes at our institution and also to report the time interval between the age of disease onset and the diagnosis of neuronal ceroid lipofuscinoses. MATERIALS AND METHODS: We investigated and analyzed the age of disease onset and neuroimaging findings (signal intensity in periventricular, deep, and subcortical white matter, thalami, basal ganglia, posterior limb of the internal capsule, insular/subinsular regions, and ventral pons; and the presence or absence of supratentorial and/or infratentorial atrophy) of patients with genetically proved neuronal ceroid lipofuscinoses at our institution. This group consisted of 24 patients who underwent 40 brain MR imaging investigations between 1993 and 2019, with a male preponderance (male/female ratio = 15:9). RESULTS: The mean ages of disease onset, first brain MR imaging, and diagnosis of neuronal ceroid lipofuscinoses were 4.70 ± 3.48 years, 6.76 ± 4.49 years, and 7.27 ± 4.78 years, respectively. Findings on initial brain MR imaging included T2/FLAIR hypointensity in the thalami (n = 22); T2/FLAIR hyperintensity in the periventricular and deep white matter (n = 22), posterior limb of the internal capsule (n = 22), ventral pons (n = 19), and insular/subinsular region (n = 18); supratentorial (n = 21) and infratentorial atrophy (n = 20). Eight of 9 patients who had follow-up neuroimaging showed progressive changes. CONCLUSIONS: We identified reported classic neuroimaging features in all except 1 patient with neuronal ceroid lipofuscinoses in our study. CLN2, CLN5, and CLN7 diseases showed predominant cerebellar-over-cerebral atrophy. We demonstrate that abnormal signal intensity in the deep white matter, posterior limb of the internal capsule, and ventral pons is more common than previously reported in the literature. We report abnormal signal intensity in the insular/subinsular region for the first time. The difference in the median time from disease onset and diagnosis was 1.5 years.
Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Lipofuscinoses Ceroides Neuronais/diagnóstico por imagem , Lipofuscinoses Ceroides Neuronais/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética/métodos , Masculino , Neuroimagem/métodos , Fenótipo , Tripeptidil-Peptidase 1RESUMO
Pyruvate dehydrogenase phosphatase deficiency has previously only been confirmed at the molecular level in two brothers and two breeds of dog with exercise intolerance. A female patient, who died at 6 months, presented with lactic acidemia in the neonatal period with serum lactate levels ranging from 2.5 to 17 mM. Failure of dichloroacetate to activate the PDH complex in skin fibroblasts was evident, but not in early passages. A homozygous c.277G > T (p.E93X) nonsense mutation in the PDP1 gene was identified in genomic DNA and immunoblotting showed a complete absence of PDP1 protein in mitochondria. Native PDHC activity could be restored by the addition of either recombinant PDP1 or PDP2. This highlights the role of PDP2, the second phosphatase isoform, in PDP1-deficient patients for the first time. We conclude that the severity of the clinical course associated with PDP1 deficiency can be quite variable depending on the exact nature of the molecular defect.
Assuntos
Códon sem Sentido , Genes Letais , Piruvato Desidrogenase (Lipoamida)-Fosfatase/deficiência , Piruvato Desidrogenase (Lipoamida)-Fosfatase/genética , Acidose Láctica/sangue , Acidose Láctica/enzimologia , Acidose Láctica/genética , Acidose Láctica/patologia , Animais , Sequência de Bases , Encéfalo/patologia , Células Cultivadas , Consanguinidade , Primers do DNA/genética , Doenças do Cão/enzimologia , Doenças do Cão/genética , Cães , Feminino , Fibroblastos/enzimologia , Homozigoto , Humanos , Lactente , Isoenzimas/deficiência , Isoenzimas/metabolismo , Ácido Láctico/sangue , Imageamento por Ressonância Magnética , Masculino , FenótipoRESUMO
A 17-month-old boy was referred with profound sensorineural hearing loss (SNHL), severe visual impairment and developmental delay. Neuroimaging identified hypomyelination and cochlear nerve aplasia. He was noted to have fair skin and hair and multiple areas of cutaneous hyperpigmentation. Previous investigations including karyotype, array comparative genomic hybridization (aCGH) and a full metabolic screen were normal. A novel missense mutation of the highly conserved high mobility group (HMG) domain of SOX10 was identified (Q174P:c.521A>C). This case represents the first description of aplasia of the cochlear nerve due to a SOX10 mutation.
Assuntos
Nervo Coclear/patologia , Mutação , Bulbo Olfatório/patologia , Fatores de Transcrição SOXE/genética , Anormalidades Múltiplas , Nervo Coclear/diagnóstico por imagem , Perda Auditiva Neurossensorial/genética , Humanos , Lactente , Masculino , Mutação de Sentido Incorreto , Bulbo Olfatório/diagnóstico por imagem , Radiografia , Análise de Sequência de DNARESUMO
We report the prenatal ultrasound and magnetic resonance imaging finding of periventricular, large subependymal pseudocysts (SEPCs) in a patient who was later diagnosed as having mitochondrial depletion syndrome (MDS). To our knowledge, this is the first report of fetal SEPCs in a patient with MDS. These findings may provide an important diagnostic tool for prenatal diagnosis of MDS in at risk pregnancies when the gene mutation causing the condition has not been delineated. It may also direct the neonatologist in the postnatal care of the newborn detected prenatally with SEPCs in view of the association of this finding with infection, chromosome abnormalities, metabolic disorders and other abnormalities, when such findings are identified serendipitously. Further research is needed to find if the SEPCs detected in our patient is an association or a coincidental finding.
Assuntos
Encefalopatias/diagnóstico , Cistos/diagnóstico , Doenças Mitocondriais/diagnóstico , Adulto , Encefalopatias/complicações , Encefalopatias/diagnóstico por imagem , Cistos/complicações , Cistos/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Doenças Mitocondriais/complicações , Gravidez , Síndrome , Ultrassonografia Pré-Natal , UrináliseRESUMO
OBJECTIVES: Rhombencephalosynapsis is a rare, but increasingly recognized, brain malformation characterized by congenital fusion of the cerebellar hemispheres and absence of the vermis. Rhombencephalosynapsis is associated with significant developmental delay, seizures and involuntary head movements. We report four cases, with correlation of prenatal and postnatal imaging and autopsy findings. METHODS: Over a 2-year period, four cases of rhombencephalosynapsis were diagnosed in the perinatal period, three in one center and one in another center. The clinical cases were reviewed, and correlation was made between the prenatal and postnatal imaging and autopsy findings where available. RESULTS: All cases presented initially with ventriculomegaly on prenatal ultrasound examination. Subsequent magnetic resonance imaging (MRI) established the diagnosis in two cases and postnatal MRI established the diagnosis in a further two cases. Autopsy was available and confirmed the diagnosis in two cases. In one case the pregnancy was terminated, two infants died in the neonatal period and one died in infancy. CONCLUSIONS: The cases in this perinatal series of rhombencephalosynapsis showed a very poor prognosis. The presence of ventriculomegaly on prenatal ultrasound imaging should alert the physician to consider rhombencephalosynapsis in the differential diagnosis. MRI appears to be the imaging modality of choice in establishing the diagnosis.
Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Cerebelo/anormalidades , Rombencéfalo/anormalidades , Adulto , Autopsia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Evolução Fatal , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Gravidez , Diagnóstico Pré-Natal , Prognóstico , Rombencéfalo/diagnóstico por imagem , Rombencéfalo/patologia , Ultrassonografia Pré-Natal/métodosRESUMO
Cytochrome c oxidase (COX) is the terminal enzyme of the respiratory chain, with subunits originating both from the mitochondrial and nuclear genome. An eleven-year-old female presented initially with a seizure followed two months later with tonic-clonic seizures, weakness and aphasia. MRI of the cerebral hemispheres showed multiple infarcts. Previous history suggested gross and fine motor control deficits with learning difficulties. A muscle biopsy showed a specific decrease of COX staining in all fibres and pleomorphic mitochondria. Respiratory chain studies confirmed an isolated complex IV defect in muscle, whilst fibroblasts showed an initial COX activity below normal which rapidly came up to the normal range on culture. Sequencing of mtDNA revealed an heteroplasmic m.7023G>A mutation in the COX1 gene, with levels of 96% in muscle, 70% in blood and 50% in the initial skin fibroblast culture dropping to 10% in later passages. The mutation was present in a critical region of the COX1 gene, the V374M change being close to the two histidine residues His376 and His378 co-ordinating with the heme a and a (3), and His367 which co-ordinates a magnesium ion. This case highlights that a MELAS-like syndrome can occur with isolated COX deficiency.