The Interplay of Cesarean-Section Delivery and First-Birth Order as Risk Factors in Acute Lymphoblastic Leukemia.

BACKGROUND: Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has been associated with early-life exposures, including birth by cesarean section (C-section), and a deficit of social exposure (first child). These exposures as proxies for microbiome acquisition in infancy are essential to prime the immune system and restrain later dysregulated immune responses that can trigger ALL in susceptible individuals. We tested risk factors pertaining to immune stimulation that may impact BCP-ALL development. METHODS: Cases comprised 1,126 children (0-12 years) with ALL (BCP-ALL: 78.5%) from the EMiLI study group in Brazil (2002-2020). Age- and sex-matched controls (n = 2,252) were randomly selected from healthy children whose mothers participated in the National Placental and Umbilical Cord Blood Bank donation. Multiple logistic regression was run fitted and adjusted for selected covariates models. RESULTS: C-section delivery was associated with increased risk for ALL [odds ratio (OR) ALL: 1.10; 95% confidence intervals (CI), 1.04-1.15; ORBCP-ALL: 1.09; 95% CI, 1.03-1.14], as well as being the firstborn child. Interaction analysis showed a significant effect of first birth on the observed C-section associations (P < 0.0001). Indeed, high-risk children, namely, firstborn children delivered via C-section were at increased risk for ALL (OR: 2.33; 95% CI, 2.40-4.84) compared with non-first, vaginally born children. An increased risk was found for firstborn children delivered by C-section and non-breastfed with ALL (ORALL: 2.32; 95% CI, 1.27-4.24; ORBCP-ALL: 2.37; 95% CI, 1.18-4.76). CONCLUSIONS: Our observations are in accord with the prediction that exposures determining microbiome composition and adrenal pathway in infancy contribute to the risk of BCP-ALL. IMPACT: These findings encourage the exploration of potential preventive interventions. See related commentary by Wiemels and Gallant, p. 292.

Interaction between birth characteristics and CRHR1, MC2R, NR3C1, GLCCI1 variants in the childhood lymphoblastic leukemia risk.

Background: The incidence rate of childhood acute lymphoblastic leukemia (ALL) differs worldwide, and the interplay between hemostasis actors and the maladaptive responses to environmental exposures has been explored. It has been proposed that endogenous cortisol, induced by different triggers, would eliminate pre-leukemic clones originated in utero. Herein, we tested if the interaction between CRHR1rs242941 C>A, MC2Rrs1893219 A>G, NR3C1rs41423247 G>C, and GLCCI1rs37972 C>T (players in glucocorticoid secretion) and birth characteristics would be associated with ALL risk. Methods: Children aged <10 years were enrolled within the EMiLI project (period: 2012 to 2020). The study had three steps: (1) observational analysis of birth characteristics (n = 533 cases and 1,603 controls); (2) genotyping to identify single-nucleotide variants (n = 756 cases and 431 controls); and (3) case-only to test gene-environment interactions (n = 402 cases). Genetic syndromes were exclusion criteria. The controls were healthy children. The distribution of the variables was assessed through Pearson's chi-square test. Logistic regression (LR) tests were run fitted and adjusted for selected covariate models to estimate the association risk. Formal interaction analysis was also performed. Genotyping was tested by qPCR with TaqMan probes (NR3C1) or by high-resolution melting (MC2R and GLCCI1). Hardy-Weinberg equilibrium (HWE) was accessed by the chi-square test. The genotype-risk association was tested in co-dominant, dominant, and recessive models. The gene-environment interaction odds ratio (iOR) was assessed in case-only. Results: Low birthweight, C-section, and low maternal schooling were associated with increased risk for ALL, adjOR 2.11, 95% CI, 1.02-4.33; adjOR 1.59, 95% CI, 1.16-2.17; and adjOR 3.78, 95% CI, 2.47-5.83, respectively, in a multiple logistic regression model. MC2R rs1893219 A>G was negatively associated with ALL (AG: OR = 0.68; 95% CI = 0.50-0.94 and GG: OR = 0.60; 95% CI = 0.42-0.85), while for GLCCI1 rs37972 C>T, TT was positively associated with ALL (OR = 1.91; 95% CI = 1.21-3.00). The combination of genotypes for MC2R (AA) and GLCCI1 (TT) increased ALL risk (OR = 2.61; 95% CI = 1.16-5.87). In a multiplicative interaction, MC2R rs1893219 A>G was associated with children whose mothers had less than 9 years of schooling (iOR = 1.99; 95% CI = 1.11-1.55). Conclusion: Our study has demonstrated a significant association between MC2R rs1893219 A>G (reduced risk) and GLCCI1 rs37972 C>T variants (increased risk) and childhood ALL susceptibility. Based on this evidence, genes controlling the HPA axis activity may play a role in leukemogenesis, and further investigation is needed to substantiate our findings.

Validation of the single-platform ISHAGE protocol for enumeration of CD34+ hematopoietic stem cells in umbilical cord blood in a Brazilian center

Abstract Background This study aims to validate the single-platform method for enumeration of CD34+ cells, by comparing the performance of two different commercial kits, as well as to evaluate the efficiency of the AccuriTM C6 cytometer in providing direct counts of absolute cell numbers. Method We evaluated 20 samples from umbilical cord blood (UCB), comparing the two different methodologies for enumeration of CD34+ cells: single and dual-platform. For the assessment of the single-platform, Procount and SCE kits were used, both of which use fluorescent beads as a counting reference to obtain absolute CD34+ cells numbers. Moreover, after the acquisition of samples in flow cytometer AccuriTM C6, following the protocol established for each kit, the number of CD34+ cells was recalculated, considering the cell count provided by the AccuriTM C6. Main Results In our analysis, the results showed a strong correlation between the number of CD34+ cells/μL (r2 = 0.77) when comparing the SCE kit and the current dual-platform method. On the other hand, the comparison between Procount kit and dual-platform results showed a moderate correlation for the number of CD34+/μL cells (r2 = 0.64). Conclusion Our results showed that the AccuriTM C6 flow cytometer can be used safely, applying both the dual and single platform analysis strategy. Considering the ISHAGE protocol-based single-platform approach, as the most appropriate methodology for CD34+ cells enumeration, our results demonstrated that the SCE kit has great potential for national standardization of UCB samples analysis methodology.

Validation of the single-platform ISHAGE protocol for enumeration of CD34+ hematopoietic stem cells in umbilical cord blood in a Brazilian center.

BACKGROUND: This study aims to validate the single-platform method for enumeration of CD34+ cells, by comparing the performance of two different commercial kits, as well as to evaluate the efficiency of the AccuriTM C6 cytometer in providing direct counts of absolute cell numbers. METHOD: We evaluated 20 samples from umbilical cord blood (UCB), comparing the two different methodologies for enumeration of CD34+ cells: single and dual-platform. For the assessment of the single-platform, Procount and SCE kits were used, both of which use fluorescent beads as a counting reference to obtain absolute CD34+ cells numbers. Moreover, after the acquisition of samples in flow cytometer AccuriTM C6, following the protocol established for each kit, the number of CD34+ cells was recalculated, considering the cell count provided by the AccuriTM C6. MAIN RESULTS: In our analysis, the results showed a strong correlation between the number of CD34+ cells/µL (r2=0.77) when comparing the SCE kit and the current dual-platform method. On the other hand, the comparison between Procount kit and dual-platform results showed a moderate correlation for the number of CD34+/µL cells (r2=0.64). CONCLUSION: Our results showed that the AccuriTM C6 flow cytometer can be used safely, applying both the dual and single platform analysis strategy. Considering the ISHAGE protocol-based single-platform approach, as the most appropriate methodology for CD34+ cells enumeration, our results demonstrated that the SCE kit has great potential for national standardization of UCB samples analysis methodology.

EPHX1 rs1051740 T>C (Tyr113His) is strongly associated with acute myeloid leukemia and KMT2A rearrangements in early age.

Experimental and epidemiological data have shown that acute myeloid leukemia in early-age (i-AML) originates prenatally. The risk association between transplacental exposure to benzene metabolites and i-AML might be influenced by genetic susceptibility. In this study, we investigated the relationship between genetic polymorphisms in CYP2E1, EPHX1, MPO, NQO1, GSTM1 and GSTT1 genes, and i-AML risk. The study included 101 i-AMLs and 416 healthy controls. Genomic DNA from study subjects was purified from bone marrow or peripheral blood aspirates and genotyped for genetic polymorphisms by real-time PCR allelic discrimination, Sanger sequencing and multiplex PCR. Crude and adjusted odds ratios (OR, adjOR, respectively) with 95% confidence intervals (95% CI) were assessed using unconditional logistic regression to estimate the magnitude of risk associations. EPHX1 rs1051740 T>C was associated with i-AML risk under the co-dominant (adjOR 3.04, P = 0.003) and recessive (adjOR 2.99, P = 0.002) models. In stratified analysis, EPHX1 rs1051740 was associated with increased risk for i-AML with KMT2A rearrangement (adjOR 3.06, P = 0.045), i-AML with megakaryocytic differentiation (adjOR 5.10, P = 0.008), and i-AML with type I mutation (adjOR 2.02, P = 0.037). EPHX1 rs1051740-rs2234922 C-G haplotype was also associated with increased risk for i-AML (adjOR 2.55, P = 0.043), and for i-AML with KMT2A rearrangement (adjOR 3.23, P = 0.034). Since EPHX1 enzyme is essential in cellular defense against epoxides, the diminished enzymatic activity conferred by the variant allele C could explain the risk associations found for i-AML. In conclusion, EPHX1 rs1051740 plays an important role in i-AML's genetic susceptibility by modulating the carcinogenic effects of epoxide exposures in the bone marrow.

Cerebrum-cervical arterial dissection in adults during sports and recreation / Dissecção arterial cérebro-cervical em adultos durante prática de esportes e recreação

Dissection of cervical arteries constitutes a medical emergency. Although relatively rarely, activities classified as sports and recreation may be a cause of arterial dissection independently of neck or head trauma. The purpose of the present paper was to present a series of cases of cerebrum-cervical arterial dissection in individuals during or soon after the practice of these sports activities. Methods Retrospective data on patients with arterial dissection related to sports and recreation. Results Forty-one cases were identified. The most frequently affected vessel was the vertebral artery. A large variety of activities had a temporal relationship to arterial dissection, and jogging was the most frequent of these. This is the largest case series in the literature. Conclusion Arterial dissection may be a complication from practicing sports.

A dissecção das artérias cervicais é uma emergência médica. Embora de forma relativamente rara, certas atividades descritas como esportes e recreação podem ser a causa de dissecção arterial independentemente de trauma de crânio ou cervical. O propósito do presente estudo é apresentar uma série de casos de dissecção de artérias cérebro-cervicais em indivíduos durante ou logo após a prática destas atividades desportivas. Métodos Dados retrospectivos de pacientes com dissecção arterial relacionada à prática de esportes e recreação. Resultados Quarenta e um casos foram identificados. A artéria mais frequentemente afetada foi a vertebral. Uma grande variedade de atividades teve relação temporal com a dissecção arterial, sendo a corrida a mais frequente delas. Esta é a maior série de casos da literatura. Conclusão Dissecção arterial pode ser uma complicação da prática de esportes.

An Efficient Electroporation Protocol for the Genetic Modification of Mammalian Cells.

Genetic modification of cell lines and primary cells is an expensive and cumbersome approach, often involving the use of viral vectors. Electroporation using square-wave generating devices, like Lonza's Nucleofector, is a widely used option, but the costs associated with the acquisition of electroporation kits and the transient transgene expression might hamper the utility of this methodology. In the present work, we show that our in-house developed buffers, termed Chicabuffers, can be efficiently used to electroporate cell lines and primary cells from murine and human origin. Using the Nucleofector II device, we electroporated 14 different cell lines and also primary cells, like mesenchymal stem cells and cord blood CD34+, providing optimized protocols for each of them. Moreover, when combined with sleeping beauty-based transposon system, long-term transgene expression could be achieved in all types of cells tested. Transgene expression was stable and did not interfere with CD34+ differentiation to committed progenitors. We also show that these buffers can be used in CRISPR-mediated editing of PDCD1 gene locus in 293T and human peripheral blood mononuclear cells. The optimized protocols reported in this study provide a suitable and cost-effective platform for the genetic modification of cells, facilitating the widespread adoption of this technology.

Cerebrum-cervical arterial dissection in adults during sports and recreation.

UNLABELLED: Dissection of cervical arteries constitutes a medical emergency. Although relatively rarely, activities classified as sports and recreation may be a cause of arterial dissection independently of neck or head trauma. The purpose of the present paper was to present a series of cases of cerebrum-cervical arterial dissection in individuals during or soon after the practice of these sports activities. METHODS: Retrospective data on patients with arterial dissection related to sports and recreation. RESULTS: Forty-one cases were identified. The most frequently affected vessel was the vertebral artery. A large variety of activities had a temporal relationship to arterial dissection, and jogging was the most frequent of these. This is the largest case series in the literature. CONCLUSION: Arterial dissection may be a complication from practicing sports.

Celularidade do sangue de cordão umbilical de gestantes hipertensas: estudo caso-controle / Cellularity of the umbilical cord blood of hypertensive pregnant women: a case control study / Celularidad de la sangre de cordón umbilical de gestantes hipertensas: estudio caso-control

OBJETIVO(S): analisar a relação entre celularidade do sangue do cordão umbilical e placentário de gestantes hipertensas e não hipertensas. MÉTODO: estudo caso-controle, com abordagem quantitativa, amostra de 73 gestantes, no período de março a setembro de 2011. Os dados fazem parte do estudo aprovado pelo Comitê de Ética em Pesquisa sob o protocolo de número 126/10. RESULTADOS: foi concluído que 80% das bolsas de sangue de cordão umbilical e placentário coletados de gestantes com hipertensão arterial apresentaram celularidade ≥5 x 108, quantidade adequada no total de células nucleadas, atendendo aos critérios estabelecidos pela Resolução 56. CONCLUSÃO: os resultados contribuíram para a identificação de fatores que possibilitam a obtenção de um quantitativo adequado de células tronco-hematopoiéticas, resultando no aumento do número de transplantes de células tronco-hematopoiéticas no Brasil.

AIM: To analyze the relationship between the cellularity of placental and umbilical cord blood of hypertensive and non-hypertensive pregnant women. METHOD: This is a case-control study that used a quantitative approach. The sample consists of 73 pregnant women and it was conducted from March to September 2011. The data are part of the study approved by the Research Ethics Committee under protocol number 126/10. RESULTS: It was found that 80% of the Umbilical Cord and placental blood bags collected from pregnant women with hypertension presented cellularity ≥5 x 108. This is the appropriate amount in relation to the totality of nucleated cells, given the criteria established by Resolution 56. CONCLUSION: The results contributed to the identification of factors that make it possible to obtain an adequate number of hematopoietic stem cells, resulting in the increased number of hematopoietic stem cell transplantation in Brazil.

OBJETIVO(S): analizar la relación entre celularidad de la sangre del cordón umbilical y placentario de gestantes hipertensas y no hipertensas. MÉTODO: estudio caso-control, con abordaje cuantitativo, muestra de 73 gestantes, en el período de marzo a septiembre de 2011. Los datos hacen parte del estudio aprobado por el Comité de Ética en Investigación bajo el protocolo de número 126/10. RESULTADOS: fue concluido que 80% de las bolsas de sangre de cordón umbilical y placentario colectados de gestantes con hipertensión arterial presentaron celularidad ≥5 x 108, cantidad adecuada en el total de células nucleadas, atendiendo a los criterios establecidos por la Resolución 56. CONCLUSIÓN: los resultados contribuyeron para la identificación de factores que posibilitan la obtención de un cuantitativo adecuado de células madre-hematopoyéticas, resultando en el aumento del número de trasplantes de células madre-hematopoyéticas en Brasil.

PON1 Q192R polymorphism (rs662) is associated with childhood embryonal tumors.

Genetic susceptibility and environment exposures are associated risk factors in carcinogenesis. Gene polymorphisms that decrease the activity of detoxifying carcinogen substances may modify the effect of exposures. We investigated whether the polymorphisms PON1 rs662 (Q192R), and PON1 rs854560 (L55M) would be associated with embryonal tumors in Brazilian children. Blood samples from 163 children with embryonal tumors and 342 as control group were genotyped by TaqMAN real-time PCR assays. Logistic regression was used to evaluate the association between the polymorphisms of cases and controls groups, adjusted by skin color and age strata. When all tumors were taken together, the presence of the PON1 rs662 (Q192R) variant genotype (RR) was associated with an increased risk of developing embryonal tumors (OR = 2.80, 95 % CI 1.12-7.02). The presence of at least one variant PON1 rs662 R allele increased the risk of developing Wilms´ Tumor although without statistical power. However, it was observed a significant association of PON1 rs662 (Q192R) variant genotype (RR) with retinoblastoma (OR = 4.08, 95 % CI 1.13-14.97), whereas the PON1 rs854560 (L55M) polymorphism was not associated with any tumor. These results indicate that PON1 polymorphisms may have an influence on the risk of developing embryonal tumors.

Evaluation of intracellular and extracellular trehalose as a cryoprotectant of stem cells obtained from umbilical cord blood.

Cord blood is a source of hematopoietic stem cells used in transplantation in which hematopoietic reconstitution is necessary. This transplant modality requires the cryopreservation of hematopoietic stem cells (HSCs). Dimethyl sulfoxide has been used as a cryoprotectant (CPA) in the cryopreservation of HSCs; however, it has been demonstrated that Me2SO exhibits toxic side effects to the human body. Due to its stability upon freezing, disaccharides such as trehalose have been investigated as a cryoprotectant. This study investigated the hypothesis that a cryopreservation solution containing intracellular and extracellular trehalose improves the recovery of stem cells after cryopreservation. After thawing, the cells were tested for their viability using the 7AAD stain, CD45+/CD34+ cells were assessed using flow cytometry and the MTT viability assay, and the proportion of hematopoietic progenitor cells was measured using the CFU assay. Our results showed the effectiveness of the solution containing intracellular and extracellular trehalose in the cryopreservation of cord blood cells, demonstrating that trehalose may be an optimal cryoprotectant when present both inside and outside of cells.

An ectopic stromal implant model for hematopoietic reconstitution and in vivo evaluation of bone marrow niches.

In adults, hematopoiesis takes places in the bone marrow, where specialized niches containing mesenchymal nonhematopoietic cells (stroma) harbor the hematopoietic stem cell (HSC). These niches are responsible and essential for the maintenance of HSCs. Attempts to expand HSCs fail to keep the general properties of stem cells, which depend on several niche components difficult to reproduce in in vitro culture systems. Here, we describe a methodology for in vivo study of hematopoietic stroma. We use stroma-loaded macroporous microcarriers implanted in the subcutaneous tissue of experimental animals and show that the ectopic stroma implant (ESI) is able to support hematopoiesis. Moreover, lethally irradiated mice can be rescued by ESI preloaded with HSCs, showing that they function as an ectopic bone marrow. ESI is also shown as a good system to study the role of different niche components. As an example, we used stromas lacking connexin 43 (Cx43) and confirm the importance of this molecule in the maintenance of the HSC niche in vivo. We believe ESI can work as an ectopic bone marrow allowing in vivo testing of different niches components and opening new avenues for the treatment of a variety of hematologic conditions particularly when stromal cell defects are the main cause of disease.

Asymmetric cortical degenerative syndromes: an integrated approach to clinical and imaging review.

BACKGROUND: The term asymmetric cortical degenerative syndromes (ACDSs) refers to any brain afflictions that result in selective atrophy, particularly with an asymmetric pattern. Regardless of the etiology, the resulting compromised profile reflects the affected topography, which correlates with the clinical findings, more than any specific neuropathologic entity. REVIEW SUMMARY: ACDS can represent a diagnostic challenge, because of an overlap of clinical manifestations, especially in the early stages. Magnetic resonance techniques are useful to understand nuclear medicine studies and to confirm areas of focal atrophy by providing anatomic details and allowing an accurate correlation with several different clinical settings. CONCLUSIONS: This article demonstrates a practical neuroradiologic approach for ACDS, including optimized imaging analysis (magnetic resonance and nuclear medicine studies), which correlates their patterns with clinical and pathologic findings of the most relevant disorders.

Células-tronco de origem hematopoéticas: expansão e perspectivas de uso terapêutico / Hematopoietic stem cells: expansion and perspectives for therapeutic use

A célula-tronco hematopoética (CTH) tem um enorme potencial para reconstituir o sistema hematopoético, o que permitiu o desenvolvimento de estratégias de terapias celulares para doenças neoplásicas ou não. Em paralelo com os avanços clínicos, estudos sobre os mecanismos moleculares que levam as células-tronco hematopoéticas a decidir pela autorrenovação, diferenciação ou apoptose têm contribuído para o conhecimento de como controlar a cinética da CTH. Esta revisão tenta descrever como estes novos avanços podem ser utilizados no desenvolvimento de estratégias de expansão das CTHs para uso terapêutico.

Hematopoietic stem cells (HSCs) have the potential for reconstituting the hematopoietic system a characteristic that has enabled the development of cell based therapies for neoplastic and non-malignant diseases. In parallel with these clinical advances, elucidation of molecular mechanisms controlling self-renewal, differentiation or apoptosis have contributed to our understanding of the molecular events that control HSC kinetics. This review focuses on how these advances can be translated in new strategies for HSC expansion and their use in therapies.

Lactate detection by MRS in mitochondrial encephalopathy: optimization of technical parameters.

Mitochondriopathies are a heterogeneous group of diseases with variable phenotypic presentation, which can range from subclinical to lethal forms. They are related either to DNA mutations or nuclear-encoded mitochondrial genes that affect the integrity and function of these organelles, compromising adenosine triphosphate (ATP) synthesis. Magnetic resonance (MR) is the most important imaging technique to detect structural and metabolic brain abnormalities in mitochondriopathies, although in some cases these studies may present normal results, or the identified brain abnormalities may be nonspecific. Magnetic resonance spectroscopy (MRS) enables the detection of high cerebral lactate levels, even when the brain has normal appearance by conventional MR scans. MRS is a useful tool for the diagnosis of mitochondriopathies, but must be correlated with clinical, neurophysiological, biochemical, histological, and molecular data to corroborate the diagnosis. Our aim is to clarify the most relevant issues related to the use of MRS in order to optimize its technical parameters, improving its use in the diagnosis of mitochondriopathies, which is often a challenge.

Pyramidal tract degeneration in multiple system atrophy: the relevance of magnetization transfer imaging.

The clinical features of multiple system atrophy (MSA) include four domains: autonomic failure/urinary dysfunction, Parkinsonism, cerebellar ataxia, and corticospinal tract dysfunction. Although the diagnosis of definite MSA requires pathological confirmation, magnetic resonance imaging (MRI) studies have been shown to contribute to the diagnosis of MSA. Although pyramidal tract dysfunction is frequent in MSA patients, signs of pyramidal tract involvement are controversially demonstrated by MRI. We evaluated the pyramidal involvement in 10 patients (7 women) with clinically probable MSA, detecting the presence of spasticity, hyperreflexia, and Babinski sign, as well as demonstrating degeneration of the pyramidal tract and primary motor cortex by MRI in all of them. Our article also discusses key radiological features of this syndrome. In MSA, pyramidal tract involvement seems to be more frequent than previously thought, and the clinicoradiological correlation between pyramidal tract dysfunction and degeneration may contribute to the understanding of the clinical hallmarks of MSA. MRI may also add information regarding the differential diagnosis of this syndrome.

Focal transient lesion in the splenium of the corpus callosum in three non-epileptic patients.

INTRODUCTION: We analyzed the imaging features of transient focal lesions in the splenium of the corpus callosum (SCC) in non-epileptic patients receiving antiepileptic drugs (AEDs). METHODS: We identified signal abnormalities in the SCC in three non-epileptic patients, all of them receiving AEDs. We examined two of these patients with multiplanar magnetic resonance (MR) imaging using 1.0-T equipment including fluid-attenuated inversion recovery (FLAIR), T2-weighted (TSE) and T1-weighted (SE) sequences before and after injection of contrast agent. The third patient was studied using 1.5-T equipment with the same sequences. Additionally, a T1 SE sequence with a magnetization transfer contrast pulse off resonance (T1 SE/MTC), diffusion-weighted imaging (EPI-DWI) and apparent diffusion coefficient (ADC) maps were obtained. RESULTS: We observed an identical pattern of imaging abnormalities in all patients characterized by round lesions, hyperintense on FLAIR and hypointense on T1 SE images, located in the central portion of the SCC. One lesion showed homogeneous gadolinium enhancement and perilesional vasogenic edema. This particular lesion showed restricted diffusion confirmed on the ADC map. This pattern was considered consistent with focal demyelination. Follow-up MR examinations showed complete disappearance or a clear reduction in lesion size. All patients had been treated with AEDs, but they did not show any clinical signs of toxicity, interhemispheric symptoms, or abnormal neurological findings (including seizures). CONCLUSION: We believe that our MR findings might be interpreted as transient lesions related to AED toxicity. They presumably resulted from focal demyelination in the central portion of the SCC.

Comparison of magnetic resonance imaging sequences with computed tomography to detect low-grade subarachnoid hemorrhage: Role of fluid-attenuated inversion recovery sequence.

OBJECTIVES: To compare computed tomography (CT) with magnetic resonance imaging (MRI) for the presumptive diagnosis and localization of acute and subacute low-grade subarachnoid hemorrhage (SAH). METHODS: We consecutively enrolled 45 patients clinically suspected of low-grade SAH, comparing them with a control group. We obtained axial nonenhanced CT scans as well as fluid-attenuated inversion recovery (FLAIR) and T2-weighted gradient echo (T2*) MRI sequences at 1.0 T. Two neuroradiologists scrutinized the presence of blood at 26 different regions in the intracranial subarachnoid space (SAS). RESULTS: Three of 45 patients had normal CT and MRI scans, and SAH was excluded by lumbar puncture. We demonstrated SAH on CT scans in 28 of 42 (66.6%) patients, T2* sequences in 15 of 42 (35.7%) patients, and FLAIR sequences in 42 of 42 (100%) patients. Fluid-attenuated inversion recovery sequences were superior to CT in 16 of the 26 evaluated regions. CONCLUSIONS: The FLAIR sequence was superior for presumptive diagnosis and localization of acute and subacute low-grade SAH, representing a potential tool in this setting.

Comparative analysis of MR sequences to detect structural brain lesions in tuberous sclerosis.

BACKGROUND: Tuberous sclerosis (TS) is a neurocutaneous genetically inherited disease with variable penetrance characterized by dysplasias and hamartomas affecting multiple organs. MR is the imaging method of choice to demonstrate structural brain lesions in TS. OBJECTIVE: To compare MR sequences and determine which is most useful for the demonstration of each type of brain lesion in TS patients. MATERIALS AND METHODS: We reviewed MR scans of 18 TS patients for the presence of cortical tubers, white matter lesions (radial bands), subependymal nodules, and subependymal giant cell astrocytoma (SGCA) on the following sequences: (1) T1-weighted spin-echo (T1 SE) images before and after gadolinium (Gd) injection; (2) nonenhanced T1 SE sequence with an additional magnetization transfer contrast medium pulse on resonance (T1 SE/MTC); and (3) fluid-attenuated inversion recovery (FLAIR) sequence. RESULTS: Cortical tubers were found in significantly (P<0.05) larger numbers and more conspicuously in FLAIR and T1 SE/MTC sequences. The T1 SE/MTC sequence was far superior to other methods in detecting white matter lesions (P<0.01). There was no significant difference between the T1 SE/MTC and T1 SE (before and after Gd injection) sequences in the detection of subependymal nodules; FLAIR sequence showed less sensitivity than the others in identifying the nodules. T1 SE sequences after Gd injection demonstrated better the limits of the SGCA. CONCLUSION: We demonstrated the importance of appropriate MRI sequences for diagnosis of the most frequent brain lesions in TS. Our study reinforces the fact that each sequence has a particular application according to the type of TS lesion. Gd injection might be useful in detecting SGCA; however, the parameters of size and location are also important for a presumptive diagnosis of these tumors.