Short communication: genetic variability in the predicted microRNA target sites of caprine casein genes.

The main goal of the current work was to identify single nucleotide polymorphisms (SNP) that might create or disrupt microRNA (miRNA) target sites in the caprine casein genes. The 3' untranslated regions of the goat alpha(S1)-, alpha(S2)-, beta-, and kappa-casein genes (CSN1S1, CSN1S2, CSN2, and CSN3, respectively) were resequenced in 25 individuals of the Murciano-Granadina, Cashmere, Canarian, Saanen, and Sahelian breeds. Five SNP were identified through this strategy: c.175C>T at CSN1S1; c.109T>C, c.139G>C, and c.160T>C at CSN1S2; and c.216C>T at CSN2. Analysis with the Patrocles Finder tool predicted that all of these SNP are located within regions complementary to the seed of diverse miRNA sequences. These in silico results suggest that polymorphism at miRNA target sites might have some effect on casein expression. We explored this issue by genotyping the c.175C>T SNP (CSN1S1) in 85 Murciano-Granadina goats with records for milk CSN1S1 concentrations. This substitution destroys a putative target site for miR-101, a miRNA known to be expressed in the bovine mammary gland. Although TT goats had higher levels (6.25 g/L) of CSN1S1 than their CT (6.05 g/L) and CC (6.04 g/L) counterparts, these differences were not significant. Experimental confirmation of the miRNA target sites predicted in the current work and performance of additional association analyses in other goat populations will be an essential step to find out if polymorphic miRNA target sites constitute an important source of variation in casein expression.

Association between the polymorphism of the goat stearoyl-CoA desaturase 1 (SCD1) gene and milk fatty acid composition in Murciano-Granadina goats.

Genetic variability of the caprine stearoyl-CoA desaturase 1 (SCD1) gene has been investigated by sequencing a 4.7-kb cDNA in 6 goats from the Murciano-Granadina and Malagueña breeds. Sequence alignment revealed the existence of one synonymous polymorphism at exon 5 (c.732C>T) and one nucleotide substitution (c.*3504G>A) at exon 6 that encodes the 3' untranslated region (UTR). Moreover, the existence of a previously reported 3'UTR polymorphism involving a 3-bp indel (c.*1902_1904delTGT) was confirmed. Single nucleotide polymorphism and haplotype-based association analyses revealed suggestive associations between genetic variability of the SCD1 locus and lactose, stearic, polyunsaturated, and conjugated linoleic fatty acid contents. Associations with milk fatty acid composition might be explained by the global effects that SCD1 exerts on mammary gland lipid metabolism through the down-modulation of key transcription factors. Interestingly, the performance of an in silico analysis revealed that the c.*1902_1904delTGT polymorphism involves a considerable change in the secondary structure of the SCD1 mRNA. Gene reporter assays and quantitative PCR analysis would be needed to assess if this mutation has a causal effect on milk polyunsaturated and conjugated linoleic fatty acid levels by altering the amount of SCD1 transcripts in mammary epithelial cells.

Short communication: Effect of alphaS1-casein (CSN1S1) and kappa-casein (CSN3) genotypes on milk composition in Murciano-Granadina goats.

The effects of the caprine alpha(S1)-casein (CSN1S1) polymorphisms on milk quality have been widely demonstrated. However, much less is known about the consequences of the kappa-casein (CSN3) genotype on milk composition in goats. Moreover, the occurrence of interactions between CSN3 and CSN1S1 genotypes has not been investigated. In this study, an association analysis between CSN1S1 and CSN3 genotypes and milk quality traits was performed in 89 Murciano-Granadina goats. Total milk yield as well as total protein, fat, solids-not-fat, lactose, alpha(S1)-casein (CSN1S1), and alpha(S2)-casein (CSN1S2) contents were recorded every other month during a whole lactation (316 observations). Data analysis using a linear mixed model for repeated observations revealed no interaction between the CSN1S1 and CSN3 genotypes. With regard to the effect of the CSN3 locus, AB and BB genotypes were significantly associated with higher levels of total casein and protein content compared with the AA CSN3 genotype. In strong contrast with French breeds, the CSN1S1 genotype did not affect protein, casein, and fat concentrations in Murciano-Granadina goats. These results highlight the importance of taking into consideration the CSN3 genotype when performing selection for milk composition in dairy goats.

Goat acetyl-coenzyme A carboxylase alpha: molecular characterization, polymorphism, and association with milk traits.

Acetyl-coenzyme A carboxylase alpha (ACACA), the major regulatory enzyme of fatty acid biosynthesis, catalyzes the conversion of acetyl-CoA to malonyl-CoA. We have sequenced 5.5 kb of the goat ACACA cDNA in 18 individuals. The translated cDNA sequence encodes 1,832 AA and shares a high AA identity (99%) with the ovine and bovine ACACA orthologous sequences. One silent single nucleotide polymorphism was identified at exon 45 (C5493T). The genotyping of this polymorphism in 4 goat breeds, Murciano-Granadina, Teramana, Majorera, and Malagueña, showed that it was segregating in all 4 breeds at variable frequencies. In addition, a mixed animal model was used to evaluate the association of C5493T genotypes with milk traits. Results from this study show that the C5493T mutation was suggestively associated with fat yield, lactose content, and somatic cell count.

Short communication: Identification of two polymorphisms in the goat lipoprotein lipase gene and their association with milk production traits.

Lipoprotein lipase (LPL) is a glycoprotein that plays a central role in plasma triglyceride metabolism by hydrolyzing triglyceride-rich chylomicrons and very low density lipoproteins. The activity of milk LPL has been shown to differ among several goat breeds, suggesting the existence of a genetic polymorphism influencing the functional properties of this enzyme. We have characterized the complete coding sequence of the goat LPL gene in 18 individuals belonging to 3 breeds. The coding region of the goat LPL cDNA was 1,437 bp long and encoded a protein of 478 amino acids. Moreover, we have identified 2 single nucleotide polymorphisms (SNP) including a G50C missense mutation, which involved a Ser-->Thr amino acid replacement at position 17 of the signal peptide, and a C2094T substitution in the 3' untranslated region. A univariate mixed model was used to evaluate the association between LPL genotypes and milk production and composition in 130 Murciano-Granadina goats. The G50C SNP was suggestively associated with milk fat content and tended to affect the milk dry weight basis. The C2094T SNP was not associated with any of the measured traits.

New estrus synchronization and artificial insemination protocol for goats based on male exposure, progesterone and cloprostenol during the non-breeding season.

This study assesses the effectiveness of a method designed to induce and synchronize ovulation in goats during the non-breeding season, allowing for systematic timed artificial insemination (AI), without the need for prior estrus detection. This method (IMA.PRO2) induces ovulation through the "male effect" and a single 25 mg dose of progesterone given at the time of buck exposure, and early lysis of the induced corpus luteum by the administration of 75 microg of cloprostenol 9 days later. The method was tested in three separate experiments. In experiment 1, estrus was detected in 87.5% of the treated goats 37.0 +/- 1.4 h after cloprostenol administration, with the preovulatory LH surge occurring 40.5 +/- 1.6 h after the cloprostenol injection. In experiment 2, data from 503 does revealed no significant differences in fertility rates between two groups inseminated 48 h (65.5+/-4.0%) or 52 h (63+/-3.0%) after receiving cloprostenol. In experiment 3, 2184 does, comprising 37 replicate groups on 12 farms, were randomly assigned to two trial subgroups. Does in the first subgroup were treated with the IMA.PRO2 method and goats from the second group were given intravaginal progestagens for 11 days, plus 350 IU of eCG and 75 microg of cloprostenol on Day 9 of this treatment. Goats from both subgroups were cervically inseminated at the same time, 50 h after cloprostenol administration in the first group and 46 h after sponge removal in the second. The pregnancy rate achieved with the new method was 64.6%, significantly higher than the yield observed for the use of progestagens plus eCG (46.8%, P<0.01). The simple method proposed as an alternative to the use of progestagen-eCG treatment provides good pregnancy rates to AI undertaken at a fixed time point, and reduces the amount of hormone needed to synchronize estrus in the animals.

Oestrous behaviour and development of preovulatory follicles in goats induced to ovulate using the male effect with and without progesterone priming.

The objective of the current study was to examine follicular dynamics in goats induced to ovulate by using the male effect with or without progesterone pretreatment. Ten Murcian-Granadina goats were treated with a single dose of 25 mg of progesterone in olive oil on the day of male effect induction (Day 0), whereas ten does remained untreated. Changes in the ovarian follicular population and onset of oestrous behaviour were checked daily from Day 0 to the day on which ovulation was detected by ultrasonography. All of the treated goats and only 20% of control goats (P < 0.001) showed oestrous behaviour between 72 and 96 h after the introduction of bucks. Differences in follicle growth were found between the groups. The control goats exhibiting oestrous behaviour during the first 4 days of ovarian screening and all of the goats treated with progesterone had their preovulatory follicles in growing phase. However, the largest follicles in control does not showing oestrus in these first 4 days were in regressing phase, being necessary for the emergence of new preovulatory follicles from a new follicular wave between Days 6 and 7, for exhibition of oestrous behaviour and subsequent ovulation. In conclusion, the appearance of short luteal phases and delayed ovulation in goats treated with the male effect during seasonal anoestrous depends on the stage of follicle development at the time of buck introduction. A single injection of progesterone stimulates the emergence of a new follicular wave, able to grow and give adequate ovulation after induction of the male effect.

[Genetic linkage analysis of Gilles de la Tourette Syndrome in a Colombian family]. / Análisis de ligamiento genético del síndrome de Gilles de la Tourette en una familia colombiana.

INTRODUCTION: Gilles de la Tourette Syndrome (GTS) is a chronic neuropsychiatric disorder characterized by phonic and motor tics. Although its physiopathologic bases are unknown, the cortical-striatal-thalamic-cortical circuit has been studied. The association of GTS with attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), motors tics (MT) or phonics tics (PT), the high family aggregation, and the concordance studies in twins, support the genetics bases of this disorder. Currently, GTS is accepted as a complex disorder and the associated disorders could be alternative expressions of the same syndrome. AIM: To evaluate genetic linkage to 2p11, 6p24, 11q23, 20q13 and 21q22 regions in an Antioquian family with enough power to detect linkage. PATIENTS AND METHODS: With the Linkage program and using autosomic dominant, recessive and additive inheritance models, the genetic linkage was calculated; two phenotypic spectra was considered: one broad spectrum including affected individuals with GTS, ADHD, OCD, MT, and PT, and a narrow spectrum with only GTS. RESULTS: The most probable inheritance pattern for a susceptibility locus in GTS and its associated disorders in this family is autosomic additive. The presence of a locus involved in GTS in the 2p11 region has been rejected. CONCLUSION: The linkage values for D20S1085 and D6S477 markers are suggestive and therefore it is not possible reject that these markers will be in linkage disequilibrium with genes involved in the GTS, ADHD, OCD, MT, and PT etiology.

Near Infrared Spectroscopy (NIRS) for the determination of the milk fat fatty acid profile of goats.

Milk fatty acid (FA) composition is important for the goat dairy industry because of its influence on cheese properties and human health. The aim of the present work was to evaluate the feasibility of NIRS reflectance (oven-dried milk using the DESIR method) and transflectance (liquid milk) analysis to predict milk FA profile and groups of fats in milk samples from individual goats. NIRS analysis of milk samples allowed to estimate FA contents and their ratios and indexes in fat with high precision and accuracy. In general, transflectance analysis gave better or similar results than reflectance mode. Interestingly, NIRS analysis allowed direct prediction of the Atherogenicity and Thrombogenicity indexes, which are useful for the interpretation of the nutritional value of goat milk. Therefore, the calibrations obtained in the present work confirm the viability of NIRS as a fast, reliable and effective analytical method to provide nutritional information of milk samples.

A novel SCN1A mutation associated with severe GEFS+ in a large South American pedigree.

Generalized epilepsy with febrile seizures plus (GEFS+) is an inherited epileptic syndrome with a marked clinical and genetic heterogeneity. Here we report the molecular characterization of a large pedigree with a severe clinical form of GEFS+. Genetic linkage analysis implied the involvement of the FEB3 in the disease phenotype of this family (parametric two-point lod-score of 2.2). Sequencing of the SCN1A gene revealed a novel aspartic acid for glycine substitution at position 1742 of this sodium channel subunit. The amino-acid replacement lies in the pore-forming region of domain IV of SCN1A. Our observations are consistent with the genotype-phenotype correlation studies suggesting that mutations in the pore-forming loop of SCN1A can lead to a clinically more severe epileptic syndrome.

Origin and fate of preovulatory follicles after induced luteolysis at different stages of the luteal phase of the oestrous cycle in goats.

The effect of day of induced luteolysis on follicle dynamics, oestrus behaviour and ovulatory response in goats was studied by administering cloprostenol on Day 5 (n=10), Day 11 (n=10), or Day 16 (n=10) after detection of oestrus. Stage of the luteal phase affected the interval from cloprostenol injection to onset of oestrus, with behavioural oestrus being observed earlier in goats treated early in the luteal phase (43.4+/-3.2 h on Day 5 versus 57.0+/-2.6 h on Day 11 and 56.7+/-2.7 h on Day 16, P<0.01). The group treated on Day 5 also tended to have a higher proportion of does which exhibited oestrus behaviour (P=0.07) and ovulation (P=0.06). In all the cycles, at least one of the ovulatory follicles arose from antral follicles present in the ovary at cloprostenol injection. In 66.7% of monovular cycles, the ovulatory follicle was the largest follicle on the day of luteolysis. In 33.3% of polyovulatory cycles, one of the ovulatory follicles was the largest one present when cloprostenol was administered. In 80% of polyovulatory cycles, the second ovulatory follicle was present on the day of luteolysis; but in the three remaining cycles, the second ovulatory follicle emerged later. This shows that the largest follicle may not exert dominance over other follicles in the goat. Evaluation of follicular dynamics in different phases of luteal activity in current experiment showed an attenuation of dominance in the mid-luteal period. In does treated early or late in the luteal phase, the number of new growing follicles decreased with time (P<0.01 and 0.05, respectively), the mean number of follicles reaching 4-5mm in size also decreased (P<0.001 and 0.01, respectively) and the number of regressing follicles increased (P<0.05). These effects did not reach statistical significance in does treated in the mid-luteal phase.

[Prevalence of attention deficit hyperactivity disorder in Colombian children and teenagers]. / Prevalencia del trastorno por déficit de atención-hiperactividad en niños y adolescentes colombianos.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioural disorder among schoolchildren. It may persist into adulthood and affect performance in the academic, social, occupational and familial spheres, and increase the use and abuse of alcohol and psychoactive substances and the risk of having an accident. Its prevalence throughout the world varies widely and further knowledge about this situation would be valuable for the development of policies in the sector of education. AIMS: The aim of this research was to determine the prevalence of ADHD and its distribution according to subtypes in schoolchildren from Sabaneta, Antioquia, Colombia, in 2001. SUBJECTS AND METHODS: The analysis involved a cross-sectional descriptive study using a representative randomised multistage sample (which was proportional to the size of the groups) of schoolchildren between 4 and 17 years old. Measurement was performed in two stages, first by application of a screening form according to DSM IV criteria, and later a structured interview, Conners' and Intelligence tests. RESULTS: Prevalence was found to be 20.4% and 15.8% if only children with an intelligence quotient of 80 or above were considered. The combined subtype was the most frequent, with 9.6%. In public schools it was 16.2%, private 15.3%, age group from 7-11 years 16.9%, 12-17 years old 14.2%, males 20.9%, females 10.1%, low 14.7%, medium 17.4% and high socioeconomic level 10.7%, with a male to female prevalence ratio of 3.88 to 1. CONCLUSIONS: Prevalence of ADHD in the school population in a municipality in the Metropolitan Area of Medellin, Colombia, is high. The most frequent subtype was the combined type, which was predominant in males, had repercussions on academic performance and low proportions of pharmacological interventions for the disorder (15%). Programmes must be developed for the detection of this problem and subsequent intervention in the school population.

Successful ultrarapid cryopreservation of wild Iberian ibex (Capra pyrenaica) spermatozoa.

A method for cryopreserving wild ibex sperm at high cooling rates was developed. To design a freezing solution based on Tris, citric acid, and glucose (TCG), two preliminary experiments were performed using glycerol (GLY) and dimethyl sulfoxide (DMSO) at different concentrations (5%, 10%, 20%). The 10% GLY + 10% DMSO combination reduced (P < 0.05) frozen-thawed sperm motility, which reached a minimum when 20% GLY + 20% DMSO was used. In the second experiment, sperm tolerance to three sucrose concentrations was evaluated (100-mM sucrose, 300-mM sucrose, 500-mM sucrose). Frozen-thawed sperm motility and sperm viability decreased (P < 0.05) at concentrations above 300 mM. The ultrarapid cooling procedure finally used involved a TCG egg yolk (ey)-based extender with 100-mM sucrose, either alone or with 5% GLY with or without BSA. Two warming procedures (37 °C vs. 60 °C) were also evaluated. The TCG ey with 100-mM sucrose but without GLY/BSA returned the best sperm quality variables. Slow warming at 37 °C strongly affected (P < 0.05) sperm motility and viability in all groups. Sperm selection by density gradient centrifugation produced no motile sperm when slow warming was performed. In contrast, when fast warming was used, sperm selection increased (P < 0.05) percentage of motility, viability, and the percentage of sperms with intact acrosomes. Heterologous in vivo fertilization involving domestic goats was performed to evaluate the in vivo fertilization capacity of the ultrarapidly cooled cryopreserved sperm (in TCG-ey + 100 mM sucrose), with warming undertaken at 60 °C. Inseminations of domestic goats resulted in three pregnancies (3 of 16, 18.7% fertility). In conclusion, ibex spermatozoa are strongly sensitive to high concentrations of permeable cryoprotectants and sucrose. However, the combination of ultrarapid cooling, using TCG-ey + 100-mM sucrose, and fast warming at 60 °C, followed by sperm selection by density gradient centrifugation to collect the motile sperm, has a positive effect on sperm viability.

Polymicrobial endocarditis involving Eikenella corrodens.

Two amphetamine abusers had polymicrobial endocarditis involving Eikenella corrodens as one of the infecting organisms. A 26-year-old woman with left-sided endocarditis due to S. aureus and Eikenella corrodens was treated successfully; however, severe mitral regurgitation resulted from the infection. In the second patient, a 29-year-old man with right-sided endocarditis, three organisms were isolated: a hemolytic Streptococcus, a non-hemolytic Streptococcus, and Eikenella corrodens. This is the first report of polymicrobial endocarditis involving Eikenella corrodens, and emphasizes the importance of this organism parenteral amphetamine abusers. Pitfalls in the diagnosis of polymicrobial endocarditis are discussed, with particular reference to the difficulties in the recognition and management of Eikenella valve infections.

Experimental streptococcal endocarditis. The early vegetation.

Aortic valve vegetation were studied in rabbits before and after intravenous injection of streptococcus mitis. Uninfected vegetation sections revealed compact eosinophilic masses with smooth-appearing edges and scattered polymorphonuclear leukocytes inside and on the surface. Scanning electron microscopic views demonstrated erythrocytes, small leukocytes, and platelets; the surface was markedly irregular. Fifteen minutes after injection of 10(10) streptococci, large mononuclear cells and polymorphonuclear leukocytes lined the vegetation edge; scanning electron microscopy showed large and small leukocytes. One and six hours after infection, there were more polymorphonuclear leukocytes inside the vegetation but few superficially. Bacteria were first seen at six hours as microcolonies inside the vegetation. Twenty-four-hour sections showed large bacterial colonies inside with few bacteria at the edges. Despite the smooth appearance of the vegetation edges, all electron microscopic views revealed very rough surfaces.

Plasma inhibin A determination at start superovulatory FSH treatments is predictive for embryo outcome in goats.

To test whether inhibin A assays can be used for the prediction of yields in embryo programmes in goats, 50 does were treated with 45 mg FGA sponges (Chronogest) for 16 days plus a single dose of 100 microg i.m. cloprostenol on Day 14, just before the start of administration of eight doses of 1.25 ml of Ovagen twice daily for 4 days. At first FSH injection, the number and size of all follicles > or =2 mm was assessed by transrectal ultrasound and plasma inhibin A levels were measured by specific dimeric assay. There was a positive correlation between number of follicles > or =6 mm (8.8 +/- 0.5) and inhibin A levels at first FSH dose (193.2 +/- 14.5 pg/ml, P<0.05). The mean number of corpora lutea on Day 7 after sponge removal was related to the total number of follicles with a diameter of 2-6 mm at the onset of the FSH treatment (15.3 +/- 0.7, P<0.05). The total number of embryos recovered was related to the number of follicles with 4-6 mm in size (6.2 +/- 0.5, P<0.05) and to the inhibin A levels at first FSH dose (P<0.05). These results suggest that follicles > or =4 mm are the source of inhibin prior to FSH stimulation and are the main source of oocytes resulting in the number of viable embryos recovered after a superovulatory treatment. Hence, the response to superovulatory treatments in goats in terms of the number of embryos can be predicted from either the population of follicles determined by ultrasound or the plasma inhibin A levels at start of the superovulatory FSH treatment.

[Cerebrovascular disease in children with sickle cell anaemia]. / Enfermedad cerebrovascular en niños con anemia de células falciformes.

INTRODUCTION: Cerebrovascular disease (CVD) is one of the most clinically devastating complications in children with sickle cell anaemia (SCA) and an important cause of death in this population. AIMS: To determine the incidence of CVD in children with SCA and to characterise the risk factors and other related clinical and imaging aspects. PATIENTS AND METHODS: We conducted a retrospective, cross sectional, descriptive study of paediatric patients with SCA and CVD that covered the period between January 1992 and February 2002. RESULTS: A total of 131 children with SCA were registered in the period between January 1992 and February 2002, during which five children suffered some kind of CVD event. This figure corresponds to 3.81% of the patients with SCA and 7.69% of the total number of children with CVD. The most frequent clinical presentation of the CVD is bouts of seizures and the most frequently observed type of CVD is ischemic, chiefly located in the middle cerebral artery. Of the different predictors that exist for ischemic CVD, haemoglobin count was found to be lower than in haemorrhagic CVD. CONCLUSION: CVD is a common complication in the progress of patients with SCA with a high percentage of neurological sequelae.

[Clinical characteristics of optical neuritis in children]. / Características clínicas de la neuritis óptica en niños.

OBJECTIVE: To describe the clinical characteristics and the visual prognosis of a group of children affected with optic neuritis. PATIENTS AND METHODS: The clinical charts of patients under 15 years of age with clinical criteria of optic neuritis were revised at the Hospital Universitario San Vicente de Pa l (Medell n, Colombia), in a time span from January 1th 1989 to December 31th 2001. RESULTS: 16 patients fulfilled the clinical criteria of optic neuritis; 50% were male and the overall mean age was 9,4 years. Seven (43,7%) patients had a preceding infectious disease two weeks earlier and only one suffered from varicella four weeks earlier. Decrease in visual acuity was present in 15 (94%) patients; 7 (44%) had headache; 7 (44%) had ocular ache and 25% had both, head and ocular ache. Neuritis was found in 28 eyes, of whom 68% had papilledema and in 32% the fundoscopic examination was normal. Bilateral affection was present in 75%. Excellent visual prognosis (20/20) was present in 19 (68%) of affected eyes; good (20/20 to 20/50) in 4 (14%), regular (20/50 to 20/100) in 2 (7%) and bad (20/200) in 11%. CONCLUSION: In our country the clinical evolution of childhood optic neuritis does not differ from that reported in other parts of the world.

[Clinical and radiological findings in two cases of aspergillosis of the central nervous system in children]. / Hallazgos clínicos y radiológicos de dos casos de aspergilosis del sistema nervioso central en niños.

INTRODUCTION: Aspergillosis is the second fungemia after candidiasis that affects the central nervous system of immunodeppresed and immunocompetent humans. The literature reports nearly always compromised adults. CASE REPORTS: Two pediatric cases of central nervous system aspergillosis with different clinical course are presented. The first of them, is a immunocompetent person in whom a granulomatous disease of the central nervous system was suspected. The cultivation of stereotaxic biopsy reported thin septated hyphae. After 42 days of treatment with itraconazol the patient recovered completely. The second patient, had an acute lymphoblastic leukemia and developed a widespread aspergillosis including the central nervous system. In spite of antifungic treatment for 63 days, he died of heart failure. CONCLUSIONS: Diagnosis of aspergillosis is difficult because of the poor specificity of the neuroimages, cerebrospinal fluid and complementary labs. The images are indistinguishable from acute ischemia infarcts and later those images change to abscesses. Direct KOH staining and the cultivation of biopsed samples confirmed the diagnosis of aspergillosis. An aggressive treatment with amphotericin B and itraconazol is recommended, but high mortality is suspected. Diagnosis, neuroimaging, clinical evolution and treatment are discussed.