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Reliable quantitative vegetation reconstructions for Europe during the Holocene are crucial to improving our understanding of landscape dynamics, making it possible to assess the past effects of environmental variables and land-use change on ecosystems and biodiversity, and mitigating their effects in the future. We present here the most spatially extensive and temporally continuous pollen-based reconstructions of plant cover in Europe (at a spatial resolution of 1° × 1°) over the Holocene (last 11.7 ka BP) using the ‘Regional Estimates of VEgetation Abundance from Large Sites’ (REVEALS) model. This study has three main aims. First, to present the most accurate and reliable generation of REVEALS reconstructions across Europe so far. This has been achieved by including a larger number of pollen records compared to former analyses, in particular from the Mediterranean area. Second, to discuss methodological issues in the quantification of past land cover by using alternative datasets of relative pollen productivities (RPPs), one of the key input parameters of REVEALS, to test model sensitivity. Finally, to validate our reconstructions with the global forest change dataset. The results suggest that the RPPs.st1 (31 taxa) dataset is best suited to producing regional vegetation cover estimates for Europe. These reconstructions offer a long-term perspective providing unique possibilities to explore spatial-temporal changes in past land cover and biodiversity.

Background Various machine learning and artificial intelligence methods have been used to predict outcomes of hospitalized COVID-19 patients. However, process mining has not yet been used for COVID-19 prediction. We developed a process mining/deep learning approach to predict mortality among COVID-19 patients and updated the prediction in 6-h intervals during the first 72 h after hospital admission. Methods The process mining/deep learning model produced temporal information related to the variables and incorporated demographic and clinical data to predict mortality. The mortality prediction was updated in 6-h intervals during the first 72 h after hospital admission. Moreover, the performance of the model was compared with published and self-developed traditional machine learning models that did not use time as a variable. The performance was compared using the Area Under the Receiver Operator Curve (AUROC), accuracy, sensitivity, and specificity. Results The proposed process mining/deep learning model outperformed the comparison models in almost all time intervals with a robust AUROC above 80% on a dataset that was imbalanced. Conclusions Our proposed process mining/deep learning model performed significantly better than commonly used machine learning approaches that ignore time information. Thus, time information should be incorporated in models to predict outcomes more accurately.

The CACNA1A gene encodes the pore-forming a(1A) subunit of the voltage-gated Ca(V)2.1 Ca(2+) channel, essential in neurotransmission, especially in Purkinje cells. Mutations in CACNA1A result in great clinical heterogeneity with progressive symptoms, paroxysmal events or both. During infancy, clinical and neuroimaging findings may be unspecific, and no dysmorphic features have been reported. We present the clinical, radiological and evolutionary features of three patients with congenital ataxia, one of them carrying a new variant. We report the structural localization of variants and their expected functional consequences. There was an improvement in cerebellar syndrome over time despite a cerebellar atrophy progression, inconsistent response to acetazolamide and positive response to methylphenidate. The patients shared distinctive facial gestalt: oval face, prominent forehead, hypertelorism, downslanting palpebral fissures and narrow nasal bridge. The two a(1A) affected residues are fully conserved throughout evolution and among the whole human Ca(V) channel family. They contribute to the channel pore and the voltage sensor segment. According to structural data analysis and available functional characterization, they are expected to exert gain- (F1394L) and loss-of-function (R1664Q/R1669Q) effect, respectively. Among the CACNA1A-related phenotypes, our results suggest that non-progressive congenital ataxia is associated with developmental delay and dysmorphic features, constituting a recognizable syndromic neurodevelopmental disorder.

Simple Summary: The idea that motivated the design of the project is to offer a genetic germline analysis to all pediatric patients diagnosed in our pediatric oncology unit. The main objective is to determine the incidence of predisposing genetic variants when studying a cohort of pediatric cancer patients using an NGS gene panel. The custom panel employed is designed to detect variants in a large number of genes involved in pediatric cancer in order to be able to identify new genotype-phenotype relationships. The data obtained are valuable for estimating the incidence of predisposing genetic alterations, due to the large number of pediatric patients included in the study. Furthermore, the novel results collected in the main document, which suggest the involvement of new genes in the predisposition to different oncological diseases, are worthwhile.Knowledge about genetic predisposition to pediatric cancer is constantly expanding. The categorization and clinical management of the best-known syndromes has been refined over the years. Meanwhile, new genes for pediatric cancer susceptibility are discovered every year. Our current work shares the results of genetically studying the germline of 170 pediatric patients diagnosed with cancer. Patients were prospectively recruited and studied using a custom panel, OncoNano V2. The well-categorized predisposing syndromes incidence was 9.4%. Likely pathogenic variants for predisposition to the patient's tumor were identified in an additional 5.9% of cases. Additionally, a high number of pathogenic variants associated with recessive diseases was detected, which required family genetic counseling as well. The clinical utility of the Jongmans MC tool was evaluated, showing a high sensitivity for detecting the best-known predisposing syndromes. Our study confirms that the Jongmans MC tool is appropriate for a rapid assessment of patients; however, the updated version of Ripperger T criteria would be more accurate. Meaningfully, based on our findings, up to 9.4% of patients would present genetic alterations predisposing to cancer. Notably, up to 20% of all patients carry germline pathogenic or likely pathogenic variants in genes related to cancer and, thereby, they also require expert genetic counseling. The most important consideration is that the detection rate of genetic causality outside Jongmans MC et al. criteria was very low.

Background: HIV-2 is a neglected virus despite estimates of 1–2 million people being infected worldwide. The virus is naturally resistant to some antiretrovirals used to treat HIV-1 and therapeutic options are limited for patients with HIV-2. Methods: In this retrospective observational study, we analysed all HIV-2-infected individuals treated with inte- grase strand transfer inhibitors (INSTIs) recorded in the Spanish HIV-2 cohort. Demographics, treatment modal- ities, laboratory values, quantitative HIV-2 RNA and CD4 counts as well as drug resistance were analysed. Results: From a total of 354 HIV-2-infected patients recruited by the Spanish HIV-2 cohort as of December 2017, INSTIs had been given to 44, in 18 as first-line therapy and in 26 after failing other antiretroviral regimens. After a median follow-up of 13 months of INSTI-based therapy, undetectable viraemia for HIV-2 was achieved in 89% of treatment-naive and in 65.4% of treatment-experienced patients. In parallel, CD4 gains were 82 and 126cells/mm3, respectively. Treatment failure occurred in 15 patients, 2 being treatment-naive and 13 treatment-experienced. INSTI resistance changes were recognized in 12 patients: N155H (5), Q148H/R (3), Y143C/G (3) and R263K (1). Conclusions: Combinations based on INSTIs are effective and safe treatment options for HIV-2-infected individ- uals. However, resistance mutations to INSTIs are selected frequently in failing patients, reducing the already limited treatment options.

Human mutations in the CACNA1A gene that encodes the pore-forming a(1A) subunit of the voltage-gated Ca(V)2.1 (P/Q-type) Ca(2+) channel cause multiple neurological disorders including sporadic and familial hemiplegic migraine, as well as cerebellar pathologies such as episodic ataxia, progressive ataxia, and early-onset cerebellar syndrome consistent with the definition of congenital ataxia (CA), with presentation before the age of 2 years. Such a pathological role is in accordance with the physiological relevance of Ca(V)2.1 in neuronal tissue, especially in the cerebellum. This review deals with the report of the main clinical features defining CA, along with the presentation of an increasing number of CACNA1A genetic variants linked to this severe cerebellar disorder in the context of Ca(2+) homeostasis alteration. Moreover, the review describes each pathological mutation according to structural location and known molecular and cellular functional effects in both heterologous expression systems and animal models. In view of this information in correlation with the clinical phenotype, we take into consideration different pathomechanisms underlying the observed motor dysfunction in CA patients carrying CACNA1A mutations. Present therapeutic management in CA and options for the development of future personalized treatment based on Ca(V)2.1 dysfunction are also discussed.

SARS-CoV-2 pandemic dimension has affected the Hospital Pediatrics Medicine assistance in our country. New challenges generated by COVID-19 require a series of proactive measures, based on existing scientific knowledge and standards of good practice, that allow the Pediatric Hospital services readiness and operability. Hospital Internal Pediatrics, as responsible of integral care of the hospitalized child, plays a leading role in the new hospital model emerging from this crisis. This review analyzes the impact of the current SARS-CoV-2 epidemic on pediatric care, and perspective of new COVID-19 outbreaks in coexistence with other viral infections. Changes secondary to pandemic involved in Hospital Pediatric units, how to prepare for future epidemics, also the involvement of pediatric units in adult care and the possible opportunities for improvement need to be revised. Assistance of patients with chronic complex conditions in epidemic circumstances, safety aspects, opportunities for teaching and ethical considerations are reviewed. The Spanish Society of Hospital Pediatrics Medicine offers with this article a series of resources for Internal Pediatric Medicine practitioners responsible to face next challenges in pediatric hospitalization units.

Objective: The International Commission on Radiological Protection (ICRP) has highlighted the large number of medical specialties using fluoroscopy outside imaging departments without programmes of radiation protection (RP) for patients and staff. Vascular surgery is one of these specialties and endovascular aneurysm repair (EVAR) is one of the most challenging procedures requiring RP guidance and optimisation actions. The recent European Directive on Basic Safety Standards requires the use and regular update of diagnostic reference levels (DRL) for interventional procedures. The objective of the study was to know the doses of patients undergoing EVAR with mobile Xray systems and with hybrid rooms (fixed Xray systems), to obtain national DRLs and suggest optimisation actions. Methods: The Spanish Chapter of Endovascular Surgery launched a national survey that involved hospitals for 10 autonomous communities representing the 77% of the Spanish population (46.7 million inhabitants). Patient dose values from mobile Xray systems were available from nine hospitals (sample of 165 EVAR procedures) and data from hybrid rooms, from seven hospitals, with dosimetric data from 123 procedures. The initial national DRLs have been obtained, as the third quartile of the median values from the different centres involved in the survey. Results: The proposed national DRLs are 278 Gy cm(2) for hybrid rooms and 87 Gy cm(2) for mobile Xray systems, and for cumulative air kerma (cumulative AK) at the patient entrance reference point, 1403 mGy for hybrid rooms, and 292 mGy for mobile systems. Conclusion: An audit of patient doses for EVAR procedures to identify optimised imaging protocol strategies is needed. It is also appropriate to evaluate the diagnostic information required for EVAR procedures. The increase by a factor of 3.2 (for kerma area product) and 4.8 (for cumulative AK) in the DRLs needs to be justified when the procedures are performed in the hybrid rooms rather than with mobile Xray systems.

The current paradigm in the nutrition sciences states that the basic nutritional unit is not the nutrients, but the foods that contain them (oils, nuts, dairy products, eggs, red or processed meats, etc.). These act as a food matrix in which the different nutrients synergistically or antagonistically modulate their effects on the various metabolic pathways determining health and disease. Food is not based on nutrients or isolated foods but on complex mixtures of one and the other that are part of a specific food pattern, a concept that has been targeted as the most pertinent to evaluate the associations between nutrition and health or disease. This document presents a summary of the available evidence on the relationship between different foods and cardiovascular health, and offers simple recommendations to be implemented in the dietary advice offered by the health professional.

The richness and uniqueness of the flora growing on gypsum substrates in Italy is known since the XIX century (Macchiati, 1888). Furthermore, the concept of plant gypsophily can be defined as the exclusiveness (or virtually exclusiveness) for living in gypsum outcropping rocks. Thus only those plant species, which show preference – or even exclusivity - for gypsum substrates, would be classified as gipsophilous (Mota et al., 2011). The main aim of this research has been the elaboration of a checklist of the Italian gypsophilous flora. The study was made possible through international collaboration between the "Mediterranea" University of Reggio Calabria (Italy) and the University of Almería (Spain). During the first step, an extensive literature review has been carried out in order to collect all available information about gypsophilous flora and to compile a preliminary list. Afterwards 18 regional botanists experts on Italian gypsum flora have been asked to rank the preference of these species for gypsum soils. Following the methodology proposed by Mota et al. (2009), the gypsophilous character of more than 100 plant species has been thus ranked on a scale ranging from 1 to 5 (with 5 representing for a total dependence on gypsum substrates). According to the obtained values, all the plant species, ranking between absolute or preferent gypsophytes, will figure in the final checklist of the gypsophytes of the whole Italian territory.

INTRODUCTION: Cancer is the leading cause of death between the first year of life and adolescence, and some types of diseases are still a major challenge in terms of cure. There is, therefore, a major need for new drugs. Recent findings in cancer biology open the door to the development of targeted therapies against individual molecular changes, as well as immunotherapy. Promising results in adult anti-cancer drug development have not yet been translated into paediatric clinical practice. A report is presented on the activity in early paediatric oncology trials (phase I-II) in Spain. MATERIAL AND METHODS: All members of the Spanish Society of Paediatric Haematology Oncology (SEHOP) were contacted in order to identify early clinical trials in paediatric cancer opened between 2005 and 2015. RESULTS: A total of 30 trials had been opened in this period: 21 (70%) in solid tumours, and 9 (30%) in malignant haemopathies. A total of 212 patients have been enrolled. The majority was industry sponsored (53%). Since 2010, four centres have joined the international consortium of Innovative Therapies for Children with Cancer (ITCC), which has as its aim to develop novel therapies for paediatric tumours. A significant number of new studies have opened since 2010, improving the treatment opportunities for our children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents, and their benefits. CONCLUSIONS: The activity in clinical trials has increased in the years analysed. The SEHOP is committed to develop and participate in collaborative academic trials, in order to help in the advancement and optimisation of existing therapies in paediatric cancer.

Late cardiomyopathy CMP is regarded as a potential severe long-term complication after anthracycline-based regimens for acute promyelocitic leukaemia (APL). We assess by MRI the incidence and severity of clinical and subclinical long-term CMP in a cohort of adult APL patients in first complete remission with PETHEMA trials. Adult patients diagnosed with APL in first complete remission lasting a 2 years underwent anamnesis and physical examination and were asked to perform a cardiac MRI. Clinical CMP was defined as radiographic and physical signs of heart failure accompanied by symptoms or by left ventricle ejection fraction (LVEF) < 45% by MRI with or without symptoms. Subclinical CMP was defined as the following MRI abnormalities: LVEF 45-50% or late gadolinium enhancement or two or more of LVEF a 55%, left ventricle end-diastolic volume index a 98 ml/m(2), left ventricle end-systolic volume index a 38 ml/m(2), right ventricle end-diastolic volume index a 106 ml/m(2) and regional wall motion abnormalities. Of the 82 patients enrolled in the study, median cumulative dose of anthracyclines (doxorubicin equivalence) was 650 mg/m(2), and median time from APL diagnosis to the study was 87 months (range, 24-195). Seven out of 57 patients with available MRI (12%) had subclinical CMP (all of them showed late gadolinium enhancement in MRI), and none had clinical CMP. Among the 25 patients without MRI, none had CMP by chest X-ray and physical assessment. In summary, we found 12% of subclinical and no clinical late CMP assessed by MRI in APL patients treated with PETHEMA protocols. Due to the low number of patients, we must interpret our results cautiously.

In mammals, melanopsin-expressing retinal ganglion cells (mRGCs) are, among other things, involved in several non-image-forming visual functions, including light entrainment of circadian rhythms. Considering the profound impact of aging on visual function and ophthalmic diseases, here we evaluate changes in mRGCs throughout the life span in humans. In 24 post-mortem retinas from anonymous human donors aged 10-81 years, we assessed the distribution, number and morphology of mRGCs by immunostaining vertical retinal sections and whole-mount retinas with antibodies against melanopsin. Human retinas showed melanopsin immunoreactivity in the cell body, axon and dendrites of a subset of ganglion cells at all ages tested. Nearly half of the mRGCs (51%) were located within the ganglion cell layer (GCL), and stratified in the outer (M1, 12%) or inner (M2, 16%) margin of the inner plexiform layer (IPL) or in both plexuses (M3, 23%). M1 and M2 cells conformed fairly irregular mosaics, while M3 cell distribution was slightly more regular. The rest of the mRGCs were more regularly arranged in the inner nuclear layer (INL) and stratified in the outer margin of the IPL (M1d, 49%). The quantity of each cell type decrease after age 70, when the total number of mRGCs was 31% lower than in donors aged 30-50 years. Moreover, in retinas with an age greater than 50 years, mRGCs evidenced a decrease in the dendritic area that was both progressive and age-dependent, as well as fewer branch points and terminal neurite tips per cell and a smaller Sholl area. After 70 years of age, the distribution profile of the mRGCs was closer to a random pattern than was observed in younger retinas. We conclude that advanced age is associated with a loss in density and dendritic arborization of the mRGCs in human retinas, possibly accounting for the more frequent occurrence of circadian rhythm disorders in elderly persons.

Azathioprine is an immunosuppressive drug that has shown effectiveness in inflammatory bowel disease treatment. Its metabolite, 6-mercaptopurine, is metabolized through thiopurine methyltransferase. Patients with low enzyme activity may have more frequent and severe side effects. The most common is leukopenia, and rarely pancytopenia. The thiopurine methyltransferase activity monitoring shows an individualized profile of enzymatic activity but it should not replace monitoring by performing serial blood counts. In patients with fever and severe neutropenia, early empirical antibiotic treatment should be initiated to prevent severe and disseminated infection. Two patients with this condition are reported.

Ewing sarcoma (ES) is an aggressive tumor defined by EWSR1 gene fusions that behave as an oncogene. Here we demonstrate that RING1B is highly expressed in primary ES tumors, and its expression is independent of the fusion oncogene. RING1B-depleted ES cells display an expression profile enriched in genes functionally involved in hematological development but RING1B depletion does not induce cellular differentiation. In ES cells, RING1B directly binds the SCN8A sodium channel promoter and its depletion results in enhanced Nav1.6 expression and function. The signaling pathway most significantly modulated by RING1B is NF-kappa B. RING1B depletion results in enhanced p105/p50 expression, which sensitizes ES cells to apoptosis by FGFR/ SHP2/STAT3 blockade. Reduced Na(V)1.6 function protects ES cells from apoptotic cell death by maintaining low NF-kappa B levels. Our findings identify RING1B as a trait of the cell-of-origin and provide a potential targetable vulnerability.

An experience with an automated infuser device at a university hospital is presented in this paper. Occupational doses at operators' fingertips were measured using optically stimulated luminescence dosemeters for two different scenarios: (i) using a semi-automatic system to prepare the fluorodesoxiglucose (FDG) injections that were delivered to the patient manually and (ii) using an automated infusion device that prepares and delivers the FDG dose. The accuracy of the activity prepared by the automatic system was also verified. Reductions in fingertip doses of 60 % using the fully automatic system have been measured. The difference between the programmed and the delivered activity was 2 %. The use of the automatic infuser in the authors' institution has led to a substantial reduction in hand radiation doses. But contamination risks, even though reduced, still exist; therefore, radioisotope manipulation should follow strict radiation protection rules to avoid incidents. Improved accuracy in dose delivery reduces chances of dose misadministration.

HIV-2 and HTLV-1 infections are globally less frequent than those produced by HIV-1, the classical AIDS agent. In Spain and up to the end of 2014, a total of 310 cases of HIV-2, 274 of HTLV-1, and 776 of HTLV-2 infections had been reported. No cases of HTLV-3 or HTLV-4 infections have been identified so far in Spain. Most persons infected with HIV-2 or HTLV-1 acknowledge epidemiological risk factors for contagion, such as originating from or living in endemic regions and/or having had sexual partners from those areas. However, risk factors could not be recognized in up to 20-25% of carriers in Spain. Thus, it seems worth keeping a high level of clinical suspicion in order to identify earlier these neglected human retroviral infections, since diagnostic procedures and antiviral treatment are specific for each of these agents. In this article we summarize the major contributions reported at the meeting of the Spanish Group for HIV-2/HTLV held in Madrid in December 2014

The equivalent dose limit for the eye lens for occupational exposure recommended by the ICRP has been reduced to 20 mSv y(-1) averaged over defined periods of 5 y, with no single year exceeding 50 mSv. The compliance with this new requirement could not be easy in some workplace such as interventional radiology and cardiology. The aim of this study is to evaluate different possible approaches in order to have a good estimate of the eye lens dose during interventional procedures. Measurements were performed with an X-ray system Philips Allura FD-10, using a PMMA phantom to simulate the patient scattered radiation and a Rando phantom to simulate the cardiologist. Thermoluminescence (TL) whole-body and TL eye lens dosemeters together with Philips DoseAware active dosemeters were located on different positions of the Rando phantom to estimate the eye lens dose in typical cardiology procedures. The results show that, for the studied conditions, any of the analysed dosemeter positions are suitable for eye lens dose assessment. However, the centre of the thyroid collar and the left ear position provide a better estimate. Furthermore, in practice, improper use of the ceiling-suspended screen can produce partial protection of some parts of the body, and thus large differences between the measured doses and the actual exposure of the eye could arise if the dosemeter is not situated close to the eye.

Benign paroxysmal torticollis of infancy (BPTI) is a rare paroxysmal disorder characterized by recurrent episodes of head tilt and accompanying general symptoms which remit spontaneously. The rare association with gain-of-function CACNA1A mutations, similar to hemiplegic migraine, has been reported. We report here two new BPTI patients from the same family carrying a heterozygous mutation in the CACNA1A gene leading to the change p.Glu533Lys. Functional analysis revealed that this mutation induces a loss of channel function due to impaired gating by voltage and much lower current density. Our data suggest that BPTI, a periodic syndrome commonly considered a migraine precursor, constitutes an age-specific manifestation of defective neuronal calcium channel activity.

Hemiplegic migraine (HM) is a rare and severe subtype of autosomal dominant migraine, characterized by a complex aura including some degree of motor weakness. Mutations in four genes (CACNA1A, ATP1A2, SCN1A and PRRT2) have been detected in familial and in sporadic cases. This genetically and clinically heterogeneous disorder is often accompanied by permanent ataxia, epileptic seizures, mental retardation, and chronic progressive cerebellar atrophy. Here we report a mutation screening in the CACNA1A and ATP1A2 genes in 18 patients with HM. Furthermore, intragenic copy number variant (CNV) analysis was performed in CACNA1A using quantitative approaches. We identified four previously described missense CACNA1A mutations (p.Ser218Leu, p.Thr501Met, p.Arg583Gln, and p.Thr666Met) and two missense changes in the ATP1A2 gene, the previously described p.Ala606Thr and the novel variant p.Glu825Lys. No structural variants were found. This genetic screening allowed the identification of more than 30% of the disease alleles, all present in a heterozygous state. Functional consequences of the CACNA1A-p.Thr501Met mutation, previously described only in association with episodic ataxia, and ATP1A2-p.Glu825Lys, were investigated by means of electrophysiological studies, cell viability assays or Western blot analysis. Our data suggest that both these variants are disease-causing.

Neuroblastoma is an embryonal tumor of neuroectodermal cells. Patients with metastatic neuroblastoma have a poor survival rate, which has led to numerous efforts to develop prognostic markers. Cancer/testis-specific antigens MAGE-A1 and MAGE-A3 genes were proposed as minimal residual disease (MRD) markers in neuroblastoma, but its usefulness for this purpose is rather limited.

[reaction: see text] Di-D-fructose 1,2':2,1'-dianhydrides, dispiro-tricyclic disaccharides widely found in food materials, have been stereoselectively prepared in one-pot reaction from O-protected D-fructose 1,2-acetonide precursors by treatment with boron trifluoride diethyl etherate. The dimerization sequence involves (i) cleavage of the anomeric acetal linkage, (ii) autoglycosylation, and (iii) final spiroketalization, the stereochemical outcome being strongly dependent on the nature of the hydroxyl protecting groups.

A high-performance liquid chromatographic method is developed for the determination of bulk sertaconazole nitrate and related compounds (potential impurities and degradation products) as well as a sertaconazole nitrate cream formulation. A 10-microns Spherisorb CN column is used along with a mobile phase consisting of acetonitrile and aqueous 0.01 M sodium phosphate (37:63, v/v). The sertaconazole nitrate peak is monitored at a wavelength of 260 nm; the retention time being 19.3 min. The detector response for sertaconazole nitrate is linear over the concentration range from 64 to 96 micrograms ml-1. The method is found to be sufficiently selective for the reliable determination of related compounds, FI-7001, FI-7009 and FI-7011, as indicated by same-day and between-day relative standard deviations (RSD) for replicate assays of 1.72% (n = 9) and 2.17% (n = 24), respectively. The application of this method to a cream formulation of sertaconazole nitrate is found to give a mean percentage recovery of 99.4% with RSD of 1.14% (n = 9); none of the cream vehicle peaks are found to interfere with the determination of sertaconazole nitrate.

Introduccion. La enfermedad de Hirschsprung (EH) o megacolon aganglionico es un trastorno congenito que se caracteriza por la ausencia de celulas ganglionares en los plexos submucosos y mioentericos intestinales, debido a un fracaso en la migracion de estas celulas desde la cresta neural (neurocrestopatia). Se han descrito disgenesias cerebrales y sindromes polimalformativos asociados a EH, lo que sugiere una morfogenesis anormal. Objetivo. Estudiar la frecuencia de malformaciones cerebrales en pacientes afectos de EH en nuestro medio. Pacientes y metodos. Estudio retrospectivo de 41.666 recien nacidos vivos, entre 1993 y 2003, de los cuales se identificaron 17 casos de EH. Resultados. La incidencia de EH en el area de salud de la provincia de Albacete es de 1,68 por cada 5.000 recien nacidos vivos. De los 17 pacientes estudiados por EH, 10 fueron aislados (58,8%) y siete (41,1%) asociados a otras anomalias estructurales y retraso psicomotor. De estos ultimos, tres se deben a cromosomopatia (trisomia 21, sindrome de Down), dos a sindromes polimalformativos especificos (un sindrome de Mowat-Wilson, y un posible sindrome FG), uno a patron de anomalias no encuadrable en entidad sindromica conocida, y uno con fenotipo normal y disgenesia cerebral aislada. En todos ellos los estudios de neuroimagen identificaron disgenesias cerebrales compatibles con trastornos de la migracion neuronal. Conclusiones. La frecuencia de asociacion de EH, bien aislada o en el contexto de un sindrome polimalformativo especifico, con trastornos de la migracion neuronal, es elevada (23,5%). Sugerimos la conveniencia de una valoracion genetica y neurologica completa en pacientes con EH, y estudios de imagen cerebral para descartar disgenesias cerebrales.

INTRODUCTION In the recent years several clinical syndromes have been recognized that are purely sensory in character and therefore the site of lesion is seemingly restricted to nerve cell bodies in the posterior root ganglia. Collectively, these disorders are referred to as sensory neuronopathies. Although they may present as distinct clinical entities with different etiologies, the severity of the clinical manifestations and outcomes varies and may overlap with those of sensory neuropathy. This similarities are better understood in the case of toxic sensory neuropathies where a dose-dependent response has been clearly demonstrated; experimentally, low doses of pyridoxine induce sensory neuropathy whereas higher doses cause neuronopathy.