Management of cerebral venous thrombosis in Spain: MOTIVATE descriptive study.

INTRODUCTION: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke that mainly affects young adults. Early, accurate diagnosis can reduce the rate and severity of complications. OBJECTIVE: The aim of this study was to analyse the clinical characteristics, management, and treatment of CVT in different centres in Spain. METHODS: We conducted a multicentre, retrospective, descriptive study of patients hospitalised due to CVT between 2008 and 2017 at 10 Spanish centres. RESULTS: We included 256 patients, with a mean age (SD) of 49.8 (18.7) years; 51% of patients were women. The most frequent symptoms were headache (73%), focal deficits (50%), epileptic seizures (33%), and encephalopathy (21%). The most frequent localisations were the superior sagittal sinus (12.5%), the transverse sinus (10.9%), and 2 or more sinuses or veins (66.4%). Thrombophilia was the most frequent known aetiology (24%), and was most commonly associated with the prothrombin G20210A mutation (19%). Forty-six percent of patients were treated with antithrombotics for 3 to 6 months, 21% for one year, and 22.6% required indefinite anticoagulation. Endovascular therapy was performed in 5% of cases, and 33% required neurosurgery. Regarding outcomes, 75% of patients were independent at 3 months (modified Rankin Scale [mRS] score ≤ 2), with papilloedema (P =  .03), focal deficits (P = .001), and encephalopathy (P < .001) showing a statistically significant association with poor prognosis (mRS > 3). The in-hospital mortality rate was 4.3%, with a 3-month mortality rate of 6.3%. CONCLUSION: The diverse risk factors and variable presentation of CVT represent a challenge in the diagnosis and treatment of this condition. To improve prognosis and reduce mortality, it is essential to establish management protocols for this entity.

Management of cerebral venous thrombosis in Spain: MOTIVATE descriptive study. / Manejo de la trombosis venosa cerebral en España: estudio descriptivo MOTIVATE.

INTRODUCTION: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke that mainly affects young adults. Early, accurate diagnosis can reduce the rate and severity of complications. OBJECTIVE: The aim of this study was to analyse the clinical characteristics, management, and treatment of CVT in different centres in Spain. METHODS: We conducted a multicentre, retrospective, descriptive study of patients hospitalised due to CVT between 2008 and 2017 at 11 Spanish centres. RESULTS: We included 256 patients, with a mean age (SD) of 49.8 (18.7) years; 51% of patients were women. The most frequent symptoms were headache (73%), focal deficits (50%), epileptic seizures (33%), and encephalopathy (21%). The most frequent localisations were the superior sagittal sinus (12.5%), the transverse sinus (10.9%), and 2 or more sinuses or veins (66.4%). Thrombophilia was the most frequent known aetiology (24%), and was most commonly associated with the prothrombin G20210A mutation (19%). Forty-six percent of patients were treated with antithrombotics for 3-6 months, 21% for one year, and 22.6% required indefinite anticoagulation. Endovascular therapy was performed in 5% of cases, and 33% required neurosurgery. Regarding outcomes, 75% of patients were independent at 3 months (modified Rankin Scale [mRS] score ≤ 2), with papilloedema (P=.03), focal deficits (P=.001), and encephalopathy (P <.001) showing a statistically significant association with poor prognosis (mRS> 3). The in-hospital mortality rate was 4.3%, with a 3-month mortality rate of 6.3%. CONCLUSION: The diverse risk factors and variable presentation of CVT represent a challenge in the diagnosis and treatment of this condition. To improve prognosis and reduce mortality, it is essential to establish management protocols for this entity.

The coagulation system helps control infection caused by the ciliate parasite Philasterides dicentrarchi in the turbot Scophthalmus maximus (L.).

Many studies have shown that coagulation systems play an important role in the defence against pathogens in invertebrates and vertebrates. In vertebrates, particularly in mammals, it has been established that the coagulation system participates in the entrapment of pathogens and activation of the early immune response. However, functional studies investigating the importance of the fish coagulation system in host defence against pathogens are scarce. In the present study, injection of turbot (Scopthalamus maximus) with the pathogenic ciliate Philasterides dicentrarchi led to the formation of macroscopic intraperitoneal clots in the fish. The clots contained abundant, immobilized ciliates, many of which were lysed. We demonstrated that the plasma clots immobilize and kill the ciliates in vitro. To test the importance of plasma clotting in ciliate killing, we inhibited the process by adding a tetrapeptide known to inhibit fibrinogen/thrombin clotting in mammals. Plasma tended to kill P. dicentrarchi slightly faster when clotting was inhibited by the tetrapeptide, although the total mortality of ciliates was similar. We also found that kaolin, a particulate activator of the intrinsic pathway in mammals, accelerates plasma clotting in turbot. In addition, PMA-stimulated neutrophils, living ciliates and several ciliate components such as cilia, proteases and DNA also displayed procoagulant activity in vitro. Injection of fish with the ciliates generated the massive release of neutrophils to the peritoneal cavity, with formation of large aggregates in those fish with live ciliates in the peritoneum. We observed, by SEM, numerous fibrin-like fibres in the peritoneal exudate, many of which were associated with peritoneal leukocytes and ciliates. Expression of the CD18/CD11b gene, an integrin associated with cell adhesion and the induction of fibrin formation, was upregulated in the peritoneal leukocytes. In conclusion, the findings of the present study show that P. dicentrarchi induces the formation of plasma clots and that the fish coagulation system may play an important role in immobilizing and killing this parasite.

[Infarction of the spinal cord and of cervical vertebral bodies following consumption of sildenafil]. / Infarto medular y de cuerpos vertebrales cervicales tras consumo de sildenafilo.

TITLE: Infarto medular y de cuerpos vertebrales cervicales tras consumo de sildenafilo.

Protocol for cryopreservation of the turbot parasite Philasterides dicentrarchi (Ciliophora, Scuticociliatia).

Philasterides dicentrarchi is a free-living marine ciliate that can become an endoparasite that causes a severe disease called scuticociliatosis in cultured fish. Long-term maintenance of this scuticociliate in the laboratory is currently only possible by subculture, with periodic passage in fish to maintain the virulence of the isolates. In this study, we developed and optimized a cryopreservation protocol similar to that used for the long-term storage of scuticociliates of the genus Miamiensis. The cryogenic medium comprised ATCC medium 1651 and a combination of 11% dimethylsulfoxide and 5% glycerol. We have verified that the most important factor ensuring the efficiency of the cryopreservation procedure is the growth phase of the culture, and that ciliates should be cryopreserved at the stationary phase (around the sixth day of culture). The cryopreservation protocol described here can be used for all strains of P. dicentrarchi as well as commercial strains of Miamiensis and enables the virulence of the strains to be maintained. Finally, this cryopreservation protocol has been shown to be more effective than others routinely applied to scuticociliates, yielding a higher survival rate with a lower initial concentration of ciliates. The results obtained indicate that the cropreservation protocol enables the long-term storage of scuticociliate parasites while maintaining the virulence of the isolates. The protocol is therefore suitable for use in vaccine production and related studies.

The Direct Referral to Endovascular Center criteria: a proposal for pre-hospital evaluation of acute stroke in the Madrid Stroke Network.

BACKGROUND AND PURPOSE: For patients with acute ischaemic stroke due to large-vessel occlusion, it has recently been shown that mechanical thrombectomy (MT) with stent retrievers is better than medical treatment alone. However, few hospitals can provide MT 24 h/day 365 days/year, and it remains unclear whether selected patients with acute stroke should be directly transferred to the nearest MT-providing hospital to prevent treatment delays. Clinical scales such as Rapid Arterial Occlusion Evaluation (RACE) have been developed to predict large-vessel occlusion at a pre-hospital level, but their predictive value for MT is low. We propose new criteria to identify patients eligible for MT, with higher accuracy. METHODS: The Direct Referral to Endovascular Center criteria were defined based on a retrospective cohort of 317 patients admitted to a stroke center. The association of age, sex, RACE scale score and blood pressure with the likelihood of receiving MT were analyzed. Cut-off points with the highest association were thereafter evaluated in a prospective cohort of 153 patients from nine stroke units comprising the Madrid Stroke Network. RESULTS: Patients with a RACE scale score ≥ 5, systolic blood pressure <190 mmHg and age <81 years showed a significantly higher probability of undergoing MT (odds ratio, 33.38; 95% confidence interval, 12-92.9). This outcome was confirmed in the prospective cohort, with 68% sensitivity, 84% specificity, 42% positive and 94% negative predictive values for MT, ruling out 83% of hemorrhagic strokes. CONCLUSIONS: The Direct Referral to Endovascular Center criteria could be useful for identifying patients suitable for MT.

Central nervous system involvement in adult patients with invasive infection caused by Streptococcus agalactiae.

INTRODUCTION: Streptococcus agalactiae is frequently an asymptomatic coloniser and a cause of neonatal and puerperal sepsis. Infections in nonpregnant adults are uncommon. The frequency of neurological complications caused by invasive infection with this microorganism in adults remains unknown. Here, we study the frequency and characteristics of central nervous system (CNS) involvement in adults with invasive S. agalactiae infection. PATIENTS AND METHODS: Review of all adults with invasive S. agalactiae infection between 2003 and 2011 in a tertiary hospital. RESULTS: S. agalactiae was isolated from blood, CSF or synovial fluid in 75 patients. Among them, 7 (9,3%) displayed neurological involvement: 5 men and 2 nonpregnant women, aged between 20 and 62 years. Diagnoses were spinal epidural abscess due to spondylodiscitis with spinal cord compression; acute bacterial meningitis; ischemic stroke as presentation of bacterial endocarditis (2 patients each); and meningoventriculitis after neurosurgery and ventricular shunting. One patient with endocarditis caused by S. agalactiae and S. aureus died in the acute phase, and another died 3 months later from metastatic cancer. The other patients recovered without sequelae. All patients had systemic predisposing factors for infection and 5 (71,4%) had experienced disruption of the mucocutaneous barrier as a possible origin of the infection. CONCLUSIONS: CNS involvement is not uncommon in adult patients with invasive infection caused by S. agalactiae. Isolating S. agalactiae, especially in cases of meningitis, should lead doctors to search for predisposing systemic disease and causes of mucocutaneous barrier disruption.

Limbic encephalitis: a clinical-radiological comparison between herpetic and autoimmune etiologies.

BACKGROUND: Herpetic (HE) and autoimmune (AE) encephalitis share clinical and radiological features. We compared both types of encephalitis with the aim of making a differential clinical-radiological pattern. MATERIALS AND METHODS: All cases with a clinical diagnosis of encephalitis who attended our hospital between 1999 and 2012 were reviewed. We selected those cases with positive polymerase chain reaction for herpes simplex virus 1 (HSV-1) in the cerebrospinal fluid (CSF), and those with antineuronal antibodies or paraneoplastic etiology. We compared epidemiological, clinical, CSF, electroencephalographic and radiological findings. RESULTS: Twelve patients with positive polymerase chain reaction for HSV-1, and 10 patients with antineuronal antibody or paraneoplastic etiology were found. The only features found exclusively in one group were the presence of psychiatric symptoms and tumors in AE. Acute onset of symptoms, fever and aphasia were more frequent in HE, which showed higher level of proteins and erythrocyte count in CSF. Neuroimaging was abnormal in all cases of HE, but only in 60% of AE. Insular and diffuse temporal lobe involvement and absence of basal ganglia involvement were more frequent in HE, and mesial temporal involvement in AE. The highest diagnostic values for differentiating HE from AE were the association of acute onset of symptoms and fever (sensitivity 0.92, specificity 1), and the absence of basal ganglia involvement (sensitivity 0.82, specificity 1). CONCLUSIONS: There are few differences between HE and AE. Psychiatric symptoms and association with tumors were unique for AE. Acute onset with fever and absence of basal ganglia involvement in magnetic resonance imaging support a diagnosis of HE.

Pharmacokinetics of netobimin and microsomal metabolism of albendazole in infected gerbils with Echinococcus granulosus.

A comparison of the pharmacokinetic profiles of netobimin (NTB), albendazole sulfoxide (ABZSO) and albendazole sulfone (ABZSO2) was performed in gerbils (Meriones unguiculatus) with intra-abdominal hydatidosis and in healthy gerbils. The infection was developed after peritoneal inoculation of protoscolices of Echinooccus granulosus from sheep. Plasma concentrations of NTB, ABZSO and ABZSO2 were measured by HPLC after oral administration of 50 mg NTB kg(-1). The results showed an incomplete biotransformation of NTB over the experimental time; and this increased in infected animals. ABZSO and ABZSO2 pharmacokinetic profiles were unaffected and were similar in both non-infected and infected animals. Both hepatic and intestinal microsomal sulfoxidase activities were measured. Since infected gerbils induced hepatic activity and decreased intestinal activity, the total activity was not different in infected and non-infected animals. In summary, intra-abdominal hydatid disease affected the pharmacokinetic profile of NTB, but ABZSO and ABZSO2 plasma concentrations were not different in infected and non-infected gerbils.

Echinococcus granulosus: membrane permeability of secondary hydatid cysts to albendazole sulfoxide.

The objectives of the present study were, first, to establish a methodology for evaluation of the permeability in vitro of hydatid cysts to different drugs and, second, to compare the permeability to albendazole sulfoxide of cysts from untreated animals, cysts from animals treated with 50 mg/kg netobimin for 5 days, and cysts from animals treated with 50 mg/kg netobimin plus 1.1 mg/kg fenbendazole for 5 days. The drug flow follows the Fick law, i.e., the uptake occurs by simple diffusion. We calculated the permeability constant of the cyst membrane by taking into account the disappearance velocity constant, the cyst area, and the incubation solution volume. The permeability value obtained for albendazole sulfoxide was 8.06+/-2.30 x 10(-6) cm s(-1) in cysts from untreated animals, 5.56+/-2.53 x l0(-6) cm s(-1) in cysts from animals treated with netobimin, and 7.05+/-3.04 x 10(-6) cm s(-1) in cysts from animals treated with netobimin +/- fenbendazole. These permeability values show significant differences (P < 0.05).

In vivo inhibition of the regenerative capacity of hydatid material after treatment with netobimin.

The effect of netobimin and netobimin plus fenbendazole administration on secondary hydatid disease was studied. Secondary hydatid disease in gerbils (Meriones unguiculatus) was produced by intraperitoneal inoculation of protoscolices of Echinococcus granulosus. The experimental animals received doses of 20 and 50 mg/kg of netobimin or a mixture of netobimin and 1.7 mg/kg of fenbendazole. The results showed that after a single dose of netobimin at the studied concentrations, the cystic material transplanted into the mouse produced a significant recurrence of the disease, but the most remarkable finding was that the hydatid-cyst recurrence never took place when netobimin was given together with fenbendazole.

[Fertility and viability study of ovine hydatid cysts]. / Estudio de la fertilidad y viabilidad de quistes hidatídicos ovinos.

BACKGROUND: The purpose of this work is to analyze the fertility of the hydatid cysts from ovine, animal species of great epidemiological interest in the hydatid disease, and the ability of the gerbil (Meriones unguiculatus) as model experimental for the study "in vivo" of this hidatyd disease as preliminary phase of therapeutic studies. METHODS: It has been carried out a study of the fertility and viability of hydatid cysts from lungs and livers of ovine from Castilla and Leon by examination and evaluation of parameters among these is the production of a secondary hydatid disease in laboratory animals. RESULTS: The total cystic index was 8.57 cysts by infested ovine (5.97 cysts by infested lung and 5.57 cysts by infested liver). The fertility percentage obtained in hydatid cysts from ovine with "in vitro" viables protoescoleces was 43.97% being 43.02% a pulmonary cysts and 46.16% in hepatic cysts. The viability of protoscoleces was demonstrated by production of a secondary hydatid disease in 100% of gerbils infested. CONCLUSIONS: It is emphasized the validity of the criteria used to study the viability "in vitro" of the protoescoleces from hydatid cysts of origin ovine. The secondary hydatid produced in gerbil leads us to consider them as experimental animal for investigation "in vivo" of hydatid disease of origin ovine.