How diverse a monocentric chromosome can be? Repeatome and centromeric organization of Juncus effusus (Juncaceae).

Juncus is the largest genus of Juncaceae and was considered holocentric for a long time. Recent findings, however, indicated that 11 species from different clades of the genus have monocentric chromosomes. Thus, the Juncus centromere organization and evolution need to be reassessed. We aimed to investigate the major repetitive DNA sequences of two accessions of Juncus effusus and its centromeric structure by employing whole-genome analyses, fluorescent in situ hybridization, CENH3 immunodetection, and chromatin immunoprecipitation sequencing. We showed that the repetitive fraction of the small J. effusus genome (~270 Mbp/1C) is mainly composed of Class I and Class II transposable elements (TEs) and satellite DNAs. Three identified satellite DNA families were mainly (peri)centromeric, with two being associated with the centromeric protein CENH3, but not strictly centromeric. Two types of centromere organization were discerned in J. effusus: type 1 was characterized by a single CENH3 domain enriched with JefSAT1-155 or JefSAT2-180, whereas type 2 showed multiple CENH3 domains interrupted by other satellites, TEs or genes. Furthermore, while type 1 centromeres showed a higher degree of satellite identity along the array, type 2 centromeres had less homogenized arrays along the multiple CENH3 domains per chromosome. Although the analyses confirmed the monocentric organization of J. effusus chromosomes, our data indicate a more dynamic arrangement of J. effusus centromeres than observed for other plant species, suggesting it may constitute a transient state between mono- and holocentricity.

Differential Repeat Accumulation in the Bimodal Karyotype of Agave L.

The genus Agave presents a bimodal karyotype with x = 30 (5L, large, +25S, small chromosomes). Bimodality within this genus is generally attributed to allopolyploidy in the ancestral form of Agavoideae. However, alternative mechanisms, such as the preferential accumulation of repetitive elements at the macrochromosomes, could also be important. Aiming to understand the role of repetitive DNA within the bimodal karyotype of Agave, genomic DNA from the commercial hybrid 11648 (2n = 2x = 60, 6.31 Gbp) was sequenced at low coverage, and the repetitive fraction was characterized. In silico analysis showed that ~67.6% of the genome is mainly composed of different LTR retrotransposon lineages and one satellite DNA family (AgSAT171). The satellite DNA localized at the centromeric regions of all chromosomes; however, stronger signals were observed for 20 of the macro- and microchromosomes. All transposable elements showed a dispersed distribution, but not uniform across the length of the chromosomes. Different distribution patterns were observed for different TE lineages, with larger accumulation at the macrochromosomes. The data indicate the differential accumulation of LTR retrotransposon lineages at the macrochromosomes, probably contributing to the bimodality. Nevertheless, the differential accumulation of the satDNA in one group of macro- and microchromosomes possibly reflects the hybrid origin of this Agave accession.

Initial Description of the Genome of Aeluropus littoralis, a Halophile Grass.

The use of wild plant species or their halophytic relatives has been considered in plant breeding programs to improve salt and drought tolerance in crop plants. Aeluropus littoralis serves as halophyte model for identification and isolation of novel stress adaptation genes. A. littoralis, a perennial monocot grass, grows in damp or arid areas, often salt-impregnated places and wasteland in cultivated areas, can survive periodically high water salinity, and tolerate high salt concentrations in the soil up to 1,100 mM sodium chloride. Therefore, it serves as valuable genetic resource to understand molecular mechanisms of stress-responses in monocots. The knowledge can potentially be used for improving tolerance to abiotic stresses in economically important crops. Several morphological, anatomical, ecological, and physiological traits of A. littoralis have been investigated so far. After watering with salt water the grass is able to excrete salt via its salt glands. Meanwhile, a number of ESTs (expressed sequence tag), genes and promoters induced by the salt and drought stresses were isolated, sequenced and annotated at a molecular level. Transfer of stress related genes to other species resulted in enhanced stress resistance. Here we describe the genome sequence and structure of A. littoralis analyzed by whole genome sequencing and histological analysis. The chromosome number was determined to be 20 (2n = 2x = 20). The genome size was calculated to be 354 Mb. This genomic information provided here, will support the functional investigation and application of novel genes improving salt stress resistance in crop plants. The utility of the sequence information is exemplified by the analysis of the DREB-transcription factor family.

A SHA-256 Hybrid-Redundancy Hardware Architecture for Detecting and Correcting Errors.

In emergent technologies, data integrity is critical for message-passing communications, where security measures and validations must be considered to prevent the entrance of invalid data, detect errors in transmissions, and prevent data loss. The SHA-256 algorithm is used to tackle these requirements. Current hardware architecture works present issues regarding real-time balance among processing, efficiency and cost, because some of them introduce significant critical paths. Besides, the SHA-256 algorithm itself considers no verification mechanisms for internal calculations and failure prevention. Hardware implementations can be affected by diverse problems, ranging from physical phenomena to interference or faults inherent to data spectra. Previous works have mainly addressed this problem through three kinds of redundancy: information, hardware, or time. To the best of our knowledge, pipelining has not been previously used to perform different hash calculations with a redundancy topic. Therefore, in this work, we present a novel hybrid architecture, implemented on a 3-stage pipeline structure, which is traditionally used to improve performance by simultaneously processing several blocks; instead, we propose using a pipeline technique for implementing hardware and time redundancies, analyzing hardware resources and performance to balance the critical path. We have improved performance at a certain clock speed, defining a data flow transformation in several sequential phases. Our architecture reported a throughput of 441.72 Mbps and 2255 LUTs, and presented an efficiency of 195.8 Kbps/LUT.

The Evolution of Cytogenetic Traits in Cuscuta (Convolvulaceae), the Genus With the Most Diverse Chromosomes in Angiosperms.

Karyotypes are characterized by traits such as chromosome number, which can change through whole-genome duplication and dysploidy. In the parasitic plant genus Cuscuta (Convolvulaceae), chromosome numbers vary more than 18-fold. In addition, species of this group show the highest diversity in terms of genome size among angiosperms, as well as a wide variation in the number and distribution of 5S and 35S ribosomal DNA (rDNA) sites. To understand its karyotypic evolution, ancestral character state reconstructions were performed for chromosome number, genome size, and position of 5S and 35S rDNA sites. Previous cytogenetic data were reviewed and complemented with original chromosome counts, genome size estimates, and rDNA distribution assessed via fluorescence in situ hybridization (FISH), for two, seven, and 10 species, respectively. Starting from an ancestral chromosome number of x = 15, duplications were inferred as the prevalent evolutionary process. However, in holocentric clade (subgenus Cuscuta), dysploidy was identified as the main evolutionary mechanism, typical of holocentric karyotypes. The ancestral genome size of Cuscuta was inferred as approximately 1C = 12 Gbp, with an average genome size of 1C = 2.8 Gbp. This indicates an expansion of the genome size relative to other Convolvulaceae, which may be linked to the parasitic lifestyle of Cuscuta. Finally, the position of rDNA sites varied mostly in species with multiple sites in the same karyotype. This feature may be related to the amplification of rDNA sites in association to other repeats present in the heterochromatin. The data suggest that different mechanisms acted in different subgenera, generating the exceptional diversity of karyotypes in Cuscuta.

An SHA-3 Hardware Architecture against Failures Based on Hamming Codes and Triple Modular Redundancy.

Cryptography has become one of the vital disciplines for information technology such as IoT (Internet Of Things), IIoT (Industrial Internet Of Things), I4.0 (Industry 4.0), and automotive applications. Some fundamental characteristics required for these applications are confidentiality, authentication, integrity, and nonrepudiation, which can be achieved using hash functions. A cryptographic hash function that provides a higher level of security is SHA-3. However, in real and modern applications, hardware implementations based on FPGA for hash functions are prone to errors due to noise and radiation since a change in the state of a bit can trigger a completely different hash output than the expected one, due to the avalanche effect or diffusion, meaning that modifying a single bit changes most of the desired bits of the hash; thus, it is vital to detect and correct any error during the algorithm execution. Current hardware solutions mainly seek to detect errors but not correct them (e.g., using parity checking or scrambling). To the best of our knowledge, there are no solutions that detect and correct errors for SHA-3 hardware implementations. This article presents the design and a comparative analysis of four FPGA architectures: two without fault tolerance and two with fault tolerance, which employ Hamming Codes to detect and correct faults for SHA-3 using an Encoder and a Decoder at the step-mapping functions level. Results show that the two hardware architectures with fault tolerance can detect up to a maximum of 120 and 240 errors, respectively, for every run of KECCAK-p, which is considered the worst case. Additionally, the paper provides a comparative analysis of these architectures with other works in the literature in terms of experimental results such as frequency, resources, throughput, and efficiency.

Trade-Off Analysis of Hardware Architectures for Channel-Quality Classification Models.

The latest generation of communication networks, such as SDVN (Software-defined vehicular network) and VANETs (Vehicular ad-hoc networks), should evaluate their communication channels to adapt their behavior. The quality of the communication in data networks depends on the behavior of the transmission channel selected to send the information. Transmission channels can be affected by diverse problems ranging from physical phenomena (e.g., weather, cosmic rays) to interference or faults inherent to data spectra. In particular, if the channel has a good transmission quality, we might maximize the bandwidth use. Otherwise, although fault-tolerant schemes degrade the transmission speed by solving errors or failures should be included, these schemes spend more energy and are slower due to requesting lost packets (recovery). In this sense, one of the open problems in communications is how to design and implement an efficient and low-power-consumption mechanism capable of sensing the quality of the channel and automatically making the adjustments to select the channel over which transmit. In this work, we present a trade-off analysis based on hardware implementation to identify if a channel has a low or high quality, implementing four machine learning algorithms: Decision Trees, Multi-Layer Perceptron, Logistic Regression, and Support Vector Machines. We obtained the best trade-off with an accuracy of 95.01% and efficiency of 9.83 Mbps/LUT (LookUp Table) with a hardware implementation of a Decision Tree algorithm with a depth of five.

Karyotype asymmetry in Cuscuta L. subgenus Pachystigma reflects its repeat DNA composition.

Cuscuta is a cytogenetically diverse genus, with karyotypes varying 18-fold in chromosome number and 127-fold in genome size. Each of its four subgenera also presents particular chromosomal features, such as bimodal karyotypes in Pachystigma. We used low coverage sequencing of the Cuscuta nitida genome (subgenus Pachystigma), as well as chromosome banding and molecular cytogenetics of three subgenus representatives, to understand the origin of bimodal karyotypes. All three species, C. nitida, C. africana (2n = 28) and C. angulata (2n = 30), showed heterochromatic bands mainly in the largest chromosome pairs. Eighteen satellite DNAs were identified in C. nitida genome, two showing similarity to mobile elements. The most abundant were present at the largest pairs, as well as the highly abundant ribosomal DNAs. The most abundant Ty1/Copia and Ty3/Gypsy elements were also highly enriched in the largest pairs, except for the Ty3/Gypsy CRM, which also labelled the pericentromeric regions of the smallest chromosomes. This accumulation of repetitive DNA in the larger pairs indicates that these sequences are largely responsible for the formation of bimodal karyotypes in the subgenus Pachystigma. The repetitive DNA fraction is directly linked to karyotype evolution in Cuscuta.

Chromosome-scale genome assembly provides insights into rye biology, evolution and agronomic potential.

Rye (Secale cereale L.) is an exceptionally climate-resilient cereal crop, used extensively to produce improved wheat varieties via introgressive hybridization and possessing the entire repertoire of genes necessary to enable hybrid breeding. Rye is allogamous and only recently domesticated, thus giving cultivated ryes access to a diverse and exploitable wild gene pool. To further enhance the agronomic potential of rye, we produced a chromosome-scale annotated assembly of the 7.9-gigabase rye genome and extensively validated its quality by using a suite of molecular genetic resources. We demonstrate applications of this resource with a broad range of investigations. We present findings on cultivated rye's incomplete genetic isolation from wild relatives, mechanisms of genome structural evolution, pathogen resistance, low-temperature tolerance, fertility control systems for hybrid breeding and the yield benefits of rye-wheat introgressions.

A Metaheuristic Optimization Approach for Parameter Estimation in Arrhythmia Classification from Unbalanced Data.

The electrocardiogram records the heart's electrical activity and generates a significant amount of data. The analysis of these data helps us to detect diseases and disorders via heart bio-signal abnormality classification. In unbalanced-data contexts, where the classes are not equally represented, the optimization and configuration of the classification models are highly complex, reflecting on the use of computational resources. Moreover, the performance of electrocardiogram classification depends on the approach and parameter estimation to generate the model with high accuracy, sensitivity, and precision. Previous works have proposed hybrid approaches and only a few implemented parameter optimization. Instead, they generally applied an empirical tuning of parameters at a data level or an algorithm level. Hence, a scheme, including metrics of sensitivity in a higher precision and accuracy scale, deserves special attention. In this article, a metaheuristic optimization approach for parameter estimations in arrhythmia classification from unbalanced data is presented. We selected an unbalanced subset of those databases to classify eight types of arrhythmia. It is important to highlight that we combined undersampling based on the clustering method (data level) and feature selection method (algorithmic level) to tackle the unbalanced class problem. To explore parameter estimation and improve the classification for our model, we compared two metaheuristic approaches based on differential evolution and particle swarm optimization. The final results showed an accuracy of 99.95%, a F1 score of 99.88%, a sensitivity of 99.87%, a precision of 99.89%, and a specificity of 99.99%, which are high, even in the presence of unbalanced data.

Does the chromosomal position of 35S rDNA sites influence their transcription? A survey on Nothoscordum species (Amaryllidaceae).

35S ribosomal DNA (rDNA) sites are the regions where the ribosomal genes 18S, 5.8S and 25S, responsible for the formation of the nucleoli, are found. The fact that rDNA sites have non-random distribution on chromosomes suggests that their positions may influence their transcription. To identify if the preferentially transcribed rDNA sites occupy specific position, six species (nine cytotypes) of the genus Nothoscordum were analyzed using two different techniques to impregnate the nucleolar organizer regions (NORs) with silver nitrate. Both techniques strongly stained NORs, but one of them also stained the proximal region of all chromosomes, suggesting the existence of another group of argentophilic proteins in this region. In species with rDNA sites in acrocentric and metacentric chromosomes, sites located on the short arms of the acrocentric chromosomes were preferentially activated. On the other hand, in species with rDNA sites restricted to the short arms of the acrocentrics, all of them were activated, whereas in those species with sites restricted to the terminal region of metacentric chromosomes, the frequency of active sites was always lower than expected. This indicate that, at least in Nothoscordum, the transcription of an rDNA site is influenced by its chromosomal position, and may explain, at least partially, the strongly non-random distribution of these sites in plant and animal chromosomes.

Evolutionary convergence or homology? Comparative cytogenomics of Caesalpinia group species (Leguminosae) reveals diversification in the pericentromeric heterochromatic composition.

MAIN CONCLUSION: We demonstrated by cytogenomic analysis that the proximal heterochromatin of the Northeast Brazilian species of Caesalpinia group is enriched with phylogenetically conserved Ty3/Gypsy-Tekay RT, but diverge in the presence of Ty3/Gypsy-Athila RT and satDNA. The Caesalpinia Group includes 225 species and 27 monophyletic genera of which four occur in Northeastern Brazil: Erythrostemon (1 sp.), Cenostigma (7 spp.), Libidibia (1 sp.), and Paubrasilia (1 sp.). The last three genera are placed in different clades in the Caesalpinia Group phylogeny, and yet they are characterized by having a numerically stable karyotype 2n = 24 (16 M+8A) and GC-rich heterochromatic bands (chromomycin A3 positive/CMA+ bands) in the proximal chromosome regions. To characterize the composition of their heterochromatin and test for the homology of these chromosomal regions, genomic DNA was extracted from Cenostigma microphyllum, Libidibia ferrea, and Paubrasilia echinata, and sequenced at low coverage using the Illumina platform. The genomic repetitive fractions were characterized using a Galaxy/RepeatExplorer-Elixir platform. The most abundant elements of each genome were chromosomally located by fluorescent in situ hybridization (FISH) and compared to the CMA+ heterochromatin distribution. The repetitive fraction of the genomes of C. microphyllum, L. ferrea, and P. echinata were estimated to be 41.70%, 38.44%, and 72.51%, respectively. Ty3/Gypsy retrotransposons (RT), specifically the Tekay lineage, were the most abundant repeats in each of the three genomes. FISH mapping revealed species-specific patterns for the Tekay elements in the proximal regions of the chromosomes, co-localized with CMA+ bands. Other species-specific patterns were observed, e.g., for the Ty3/Gypsy RT Athila elements which were found in all the proximal heterochromatin of L. ferrea or restricted to the acrocentric chromosomes of C. microphyllum. This Athila labeling co-localized with satellite DNAs (satDNAs). Although the Caesalpinia Group diverged around 55 Mya, our results suggest an ancestral colonization of Tekay RT in the proximal heterochromatin. Thus, the present-day composition of the pericentromeric heterochromatin in these Northeast Brazilian species is a combination of the maintenance of an ancestral Tekay distribution with a species-specific accumulation of other repeats.

Together But Different: The Subgenomes of the Bimodal Eleutherine Karyotypes Are Differentially Organized.

Bimodal karyotypes are characterized by the presence of two sets of chromosomes of contrasting size. Eleutherine bulbosa (2n = 12) presents a bimodal karyotype with a large chromosome pair, which has a pericentric inversion in permanent heterozygosity with suppressed recombination, and five pairs of three to four times smaller chromosomes. Aiming to understand whether high copy number sequence composition differs between both chromosome sets, we investigated the repetitive DNA fraction of E. bulbosa and compared it to the chromosomal organization of the related Eleutherine latifolia species, not containing the pericentric inversion. We also compared the repetitive sequence proportions between the heteromorphic large chromosomes of E. bulbosa and between E. bulbosa and E. latifolia to understand the influence of the chromosome inversion on the dynamics of repetitive sequences. The most abundant repetitive families of the genome showed a similar chromosomal distribution in both homologs of the large pair and in both species, apparently not influenced by the species-specific inversions. The repeat families Ebusat1 and Ebusat4 are localized interstitially only on the large chromosome pair, while Ebusat2 is located in the centromeric region of all chromosomes. The four most abundant retrotransposon lineages are accumulated in the large chromosome pair. Replication timing and distribution of epigenetic and transcriptional marks differ between large and small chromosomes. The differential distribution of retroelements appears to be related to the bimodal condition and is not influenced by the nonrecombining chromosome inversions in these species. Thus, the large and small chromosome subgenomes of the bimodal Eleutherine karyotype are differentially organized and probably evolved by repetitive sequences accumulation on the large chromosome set.

Positive association between leptin serum levels and disease activity on endoscopy in inflammatory bowel disease: A case-control study.

Inflammatory bowel disease (IBD) includes ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis. As these subtypes of IBD display important differences in the behavior of the natural course of the disease, the identification of non-invasive markers for IBD is important. The aim of the present study was to evaluate the serum levels of 10 adipokines and their association with endoscopic activity in IBD. The 10-protein profile (C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin) was evaluated using serum from 53 participants (23 UC and 11 CD patients, as well as 19 controls) from Zacatecas (Mexico) by using the Bio-Plex Pro Human Diabetes 10-Plex Panel (Bio-Rad Laboratories, Inc.). Compared with those in the controls, leptin levels were significantly lower in patients with IBD (P=4.9×10-4). In addition, serum leptin displayed differences between groups with and without disease activity on endoscopy (P<0.001). Among the study population, serum leptin levels of <5,494 pg/ml significantly increased the odds of IBD by 12.8-fold [odds ratio (OR)=12.8, 95% confidence interval (CI)=3.04-53.9, P=0.001]. In addition, patients with serum leptin levels of <2,498 pg/ml displayed 5.8-fold greater odds of disease activity on endoscopy among the study population (OR=5.8, 95% CI=1.52-22.4, P=0.013). No differences in the serum levels of the remaining proteins were identified between the groups. Among the study population, serum leptin was associated with an increased risk of IBD and with disease activity on endoscopy. Additional studies will be necessary to validate the use of leptin as a non-invasive biomarker of IBD severity.

[Utility of 11C-methionine PET/CT in neuro-oncology]. / Utilidad de 11C-metionina PET/CT en neurooncología.

Positron emission tomography (PET) with 11C-methionine (11C-methionine PET/CT) is a new technique used to evaluate primary central nervous system (CNS) tumors. We describe our experience regarding the first 4 patients with glial tumors and 11C-methionine PET/CT. This is a descriptive, observational and prospective study of 4 patients between 38-50 years of age, with different gliomas (WHO classification). MRI and 11C-methionine PET/CT were performed in all cases. Case 1, gliomatosis cerebri grade II post-radiotherapy. Case 2, oligodendroglioma grade II diagnosed and treated with radiotherapy in 1993. Case 3, glioblastoma grade IV post-radiotherapy + temozolomide. Case 4, anaplastic oligoastrocytoma grade III post-radiotherapy + temozolomide. The pattern of 11C-methionine uptake compared with MRI showed tumor progression in cases 1, 3 and 4, and in case 2 showed uptake although the final diagnosis was pseudoprogression. Unlike 18fluordeoxiglucose PET/TC, 11C-methionine uptake in normal brain tissue and pseudoprogression is low, and gliomas are displayed as metabolically active areas. The 11C-methionine PET/CT provided valuable information on the tumoral behavior and extension, although in one case presented did not differentiate tumor progression from pseudoprogression. 11C-methionine PET/CT could be a useful tool in the study and follow-up to patients with gliomas.

Utilidad de 11C-metionina PET/CT en neurooncología / Utility of 11C-methionine PET/CT in neuro-oncology

La tomografía por emisión de positrones con metionina carbono 11 (11C-metionina PET/TC) se utiliza en la evaluación de los tumores primarios del sistema nervioso central. Describimos nuestra experiencia sobre los primeros 4 pacientes con tumores de la serie glial estudiados con 11C-metionina PET/TC. Este es un estudio descriptivo, observacional y prospectivo. Se presentan 4 pacientes entre 38-50 años de edad con diagnóstico de gliomas (clasificación de la OMS). A todos se les realizó RM y 11C-metionina PET/TC para evaluar actividad tumoral y diferenciar progresión tumoral de pseudoprogresión. Caso 1, gliomatosis cerebri grado II posradioterapia. Caso 2, glioblastoma grado IV postratamiento RT + temozolomida. Caso 3, oligodendroglioma grado II posradioterapia en 1993. Caso 4, oligoastrocitoma anaplásico grado III postratamiento RT + temozolomida. El patrón de captación de la 11C-metionina comparativamente con la RM, demostró progresión tumoral en los casos 1, 3 y 4; en el caso 2 mostró captación aunque el diagnóstico final fue pseudoprogresión. A diferencia del PET con 18fluordeoxiglucosa, la captación de 11C-metionina en el tejido cerebral normal y en la pseudoprogresión es baja, y los gliomas se visualizan como áreas metabólicamente activas. En los casos presentados, el 11C-metionina PET/TC proveyó información valiosa sobre el comportamiento y extensión de la lesión, aunque en uno de los casos presentados no diferenció progresión tumoral de pseudoprogresión. El 11C-metionina PET/TC sería una herramienta útil en el estudio y seguimiento de los pacientes con gliomas.

Positron emission tomography (PET) with 11C-methionine (11C-methionine PET/CT) is a new technique used to evaluate primary central nervous system (CNS) tumors. We describe our experience regarding the first 4 patients with glial tumors and 11C-methionine PET/CT. This is a descriptive, observational and prospective study of 4 patients between 38-50 years of age, with different gliomas (WHO classification). MRI and 11C-methionine PET/CT were performed in all cases. Case 1, gliomatosis cerebri grade II post-radiotherapy. Case 2, oligodendroglioma grade II diagnosed and treated with radiotherapy in 1993. Case 3, glioblastoma grade IV post-radiotherapy + temozolomide. Case 4, anaplastic oligoastrocytoma grade III post-radiotherapy + temozolomide. The pattern of 11C-methionine uptake compared with MRI showed tumor progression in cases 1, 3 and 4, and in case 2 showed uptake although the final diagnosis was pseudoprogression. Unlike 18fluordeoxiglucose PET/TC, 11C-methionine uptake in normal brain tissue and pseudoprogression is low, and gliomas are displayed as metabolically active areas. The 11C-methionine PET/CT provided valuable information on the tumoral behavior and extension, although in one case presented did not differentiate tumor progression from pseudoprogression. 11C-methionine PET/CT could be a useful tool in the study and follow-up to patients with gliomas.

[Neuromyelitis optica with high aquaporin-4 expression and positive serum aquaporin-4 autoantibodies]. / Neuromielitis óptica con alta expresión de acuaporina-4 y anticuerpos anti-acuaporina-4 positivos en suero.

Disease-specific aquaporin-4 antibodies (NMO-IgG) are the main effector of lesions in neuromyelitis optica (NMO) patients. Brain MRI lesions are detected in 60% of them, with 8% (almost infants) at sites of high aquaporin-4 expression. Patient 1: A fifty-year-old male with loss of vision in the right eye. Empiric treatment with metilprednisolone 1g/d for 3 days was indicated. After 30 days he complained of generalized pain, and a right hemiparesis was evident. The patient received bolus of metilprednisolone 1g/d for 5 days plus IgG 400 mg/kg/d IV for 5 days. He recovered ambulation but persisted with pain and paroxysmal phenomena (Lhermitte). Visual Evoked Potentials (VEP): P100 left eye 123 ms, right eye without response. Brain MRI (FLAIR) showed hyperintensity in the right optic nerve, hypothalamus and anterior white commissure. Cervical MRI showed extensive spinal cord lesion to an extension of 5 vertebral bodies. Patient 2: A fifty-three-year-old female who referred decreased visual acuity in both eyes and paresthesia in lower limbs which subsided spontaneously. One month later the patient evolved with cuadriparesis and sphincter incontinence. No improvement was observed with bolus of metilprednisolone 1g/d for 5 day. VEP: P100 left eye 124 ms, right eye 128 ms. Brain MRI (FLAIR) disclosed hypothalamic and periaqueductal hyperintensity. Cervical MRI showed extensive spinal cord lesion to an extension of 7 vertebral bodies. NMO-IgG antibodies were positive in both patients (indirect immunofluorescence assay). NMO brain lesions at sites of high aquaporin-4 expression, once considered atypical for their topography and infrequency in adults, should be borne in mind when considering differential diagnosis.

Neuromielitis óptica con alta expresión de acuaporina-4 y anticuerpos anti-acuaporina-4 positivos en suero / Neuromyelitis optica with high aquaporin-4 expression and positive serum aquaporin-4 autoantibodies

La presencia de anticuerpos IgG en suero, con blanco en los canales de acuaporina-4, es específica de la neuromielitis óptica (NMO). El 60% de los pacientes con NMO presentan lesiones cerebrales en la resonancia magnética (RM); en un 8% (mayoría niños) estas lesiones se consideraron "atípicas". Presentamos dos pacientes con NMO y lesiones en el SNC de alta expresión de acuaporina-4. Caso 1: varón de 50 años, que comenzó con pérdida de visión en ojo derecho (OD). Recibió tratamiento empírico con metilprednisolona 1 g/d x 3 días. Al mes presentó dolor generalizado y hemiparesia derecha; nuevamente recibió metilprednisolona 1 g/d x 5 días e IgG IV 400 mg/kg/d × 5 días. Recuperó la deambulación persistiendo el dolor y fenómenos paroxísticos en los 4 miembros. Potenciales evocados visuales: P100, ojo izquierdo (OI) 123 mseg. OD sin respuesta. La RM de cerebro (FLAIR) mostró hiperintensidad en nervio óptico derecho, hipotálamo y comisura blanca anterior. RM cervical: lesión medular extensa (5 cuerpos vertebrales). Caso 2: mujer de 53 años, con disminución de la agudeza visual en ambos ojos y parestesias en miembros inferiores que remitieron espontáneamente. Evolucionó al mes con cuadriparesia e incontinencia esfinteriana. Recibió metilprednisolona 1 g/d x 5 días, sin mejoría. Potenciales evocados visuales: P100 OI 124 mseg. OD 128 mseg. RM cerebro: (FLAIR) hiperintensidad hipotalámica y periacueductal. RM cervical: lesión medular extensa (7 cuerpos vertebrales). Anticuerpos anti-acuaporina-4 positivos en ambos pacientes (inmunofluorescencia indirecta). Las lesiones consideradas "atípicas", como aquí, en sitios con alta densidad de proteínas canales de agua AQP4 deberán considerarse para el diagnóstico diferencial.

Disease-specific aquaporin-4 antibodies (NMO-IgG) are the main effector of lesions in neuromyelitis optica (NMO) patients. Brain MRI lesions are detected in 60% of them, with 8% (almost infants) at sites of high aquaporin-4 expression. Patient 1: A fifty-year-old male with loss of vision in the right eye. Empiric treatment with metilprednisolone 1g/d for 3 days was indicated. After 30 days he complained of generalized pain, and a right hemiparesis was evident. The patient received bolus of metilprednisolone 1g/d for 5 days plus IgG 400 mg/kg/d IV for 5 days. He recovered ambulation but persisted with pain and paroxysmal phenomena (Lhermitte). Visual Evoked Potentials (VEP): P100 left eye 123 ms, right eye without response. Brain MRI (FLAIR) showed hyperintensity in the right optic nerve, hypothalamus and anterior white commissure. Cervical MRI showed extensive spinal cord lesion to an extension of 5 vertebral bodies. Patient 2: A fifty-three-year-old female who referred decreased visual acuity in both eyes and paresthesia in lower limbs which subsided spontaneously. One month later the patient evolved with cuadriparesis and sphincter incontinence. No improvement was observed with bolus of metilprednisolone 1g/d for 5 day. VEP: P100 left eye 124 ms, right eye 128 ms. Brain MRI (FLAIR) disclosed hypothalamic and periaqueductal hyperintensity. Cervical MRI showed extensive spinal cord lesion to an extension of 7 vertebral bodies. NMO-IgG antibodies were positive in both patients (indirect immunofluorescence assay). NMO brain lesions at sites of high aquaporin-4 expression, once considered "atypical" for their topography and infrequency in adults, should be borne in mind when considering differential diagnosis.