Neuroinvasive disease due to West Nile virus: Clinical and imaging findings associated with a re-emerging pathogen.

The West Nile virus (WNV) is an arbovirus than can infect human beings and cause severe neuroinvasive disease. Taking the outbreak that occurred in Spain in 2020 as a reference, this article reviews the clinical and imaging findings for neuroinvasive disease due to WNV. We collected demographic, clinical, laboratory, and imaging (CT and MRI) variables for 30 patients with WNV infection diagnosed at our center. The main clinical findings were fever, headache, and altered levels of consciousness. Neuroimaging studies, especially MRI, are very useful in the diagnosis and follow-up of these patients. The most common imaging findings were foci of increased signal intensity in the thalamus and brainstem in T2-weighted sequences; we illustrate these findings in cases from our hospital.

Neuroinvasive disease due to West Nile virus: clinical and imaging findings associated with a re-emerging pathogen. / Enfermedad neuroinvasiva por el virus del Nilo Occidental: características clínicas y en neuroimagen de un patógeno reemergente.

The West Nile virus (WNV) is an arbovirus than can infect human beings and cause severe neuroinvasive disease. Taking the outbreak that occurred in Spain in 2020 as a reference, this article reviews the clinical and imaging findings for neuroinvasive disease due to WNV. We collected demographic, clinical, laboratory, and imaging (CT and MRI) variables for 30 patients with WNV infection diagnosed at our center. The main clinical findings were fever, headache, and altered levels of consciousness. Neuroimaging studies, especially MRI, are very useful in the diagnosis and follow-up of these patients. The most common imaging findings were foci of increased signal intensity in the thalamus and brainstem in T2-weighted sequences; we illustrate these findings in cases from our hospital.

Characteristics of a Diverse Cohort of Stroke Patients with SARS-CoV-2 and Outcome by Sex.

BACKGROUND AND PURPOSE: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with stroke. The role of sex on stroke outcome has not been investigated. To objective of this paper is to describe the characteristics of a diverse cohort of acute stroke patients with COVID-19 disease and determine the role of sex on outcome. METHODS: This is a retrospective study of patients with acute stroke and SARS-CoV-2 infection admitted between March 15 to May 15, 2020 to one of the six participating comprehensive stroke centers. Baseline characteristics, stroke subtype, workup, treatment and outcome are presented as total number and percentage or median and interquartile range. Outcome at discharge was determined by the modified Rankin Scale Score (mRS). Variables and outcomes were compared for males and females using univariate and multivariate analysis. RESULTS: The study included 83 patients, 47% of which were Black, 28% Hispanics/Latinos, and 16% whites. Median age was 64 years. Approximately 89% had at least one preexisting vascular risk factor (VRF). The most common complications were respiratory failure (59%) and septic shock (34%). Compared with females, a higher proportion of males experienced severe SARS-CoV-2 symptoms requiring ICU hospitalization (73% vs. 49%; p = 0.04). When divided by stroke subtype, there were 77% ischemic, 19% intracerebral hemorrhage and 3% subarachnoid hemorrhage. The most common ischemic stroke etiologies were cryptogenic (39%) and cardioembolic (27%). Compared with females, males had higher mortality (38% vs. 13%; p = 0.02) and were less likely to be discharged home (12% vs. 33%; p = 0.04). After adjustment for age, race/ethnicity, and number of VRFs, mRS was higher in males than in females (OR = 1.47, 95% CI = 1.03-2.09). CONCLUSION: In this cohort of SARS-CoV-2 stroke patients, most had clinical evidence of coronavirus infection on admission and preexisting VRFs. Severe in-hospital complications and worse outcomes after ischemic strokes were higher in males, than females.

No evidence of association between functional polymorphisms located within IL6R and IL6ST genes and systemic sclerosis.

Systemic sclerosis (SSc) is a complex autoimmune disease which genetic component has not been yet completely understood. IL6 encodes a cytokine with a crucial role in the development of autoimmunity and fibrosis and its actions mainly are controlled by IL-6 receptor (IL-6R). We aimed to investigate whether the functional genetic variants rs8192284 and rs2228044 previously associated with several autoimmune diseases, located within the IL-6 receptor (IL-6R) subunits IL6R and IL6ST genes, respectively, are involved in the susceptibility to SSc and/or its major clinical subphenotypes. A Spanish cohort including 1013 SSc patients and 1375 controls was genotyped using the TaqMan® allelic discrimination technology. SSc patients were subdivided according to the major clinical forms, autoantibody status and presence of fibrotic lung affection. Our data showed no influence of the selected variants in global SSc susceptibility (rs8192284: P=0.67, odds ratios (OR)=0.98; rs2228044: P=0.99, OR=1.00). Similarly, the clinical/autoantibody subphenotype analyses did not yielded significant results. Our data suggest that the analyzed polymorphisms may not play a significant role in the SSc susceptibility.

Contenido en filtros tras angioplastia y colocación de stent carotídeo: relación con lesiones isquémicas en la resonancia magnética de difusión / Filter content after carotid angioplasty and stenting: relation to ischemic lesions in diffusion-weighted imaging

Objetivos. Evaluar la relación entre el material recogido en filtros distales tras angioplastia y colocación de stent carotídeo (ASC) y la aparición de lesiones isquémicas cerebrales en la RM potenciada en difusión (RMD). Determinar la influencia que tienen variables demográficas, clínicas y del procedimiento en el proceso embolígeno y en la isquemia post-ASC. Material y método. Se analizó histológicamente el contenido de los filtros de 76 pacientes sometidos a ASC por estenosis grave de la arteria carótida interna (ACI) (60 hombres; edad media 68,39 años; rango: 46-82), valorándose el volumen (< 1 λ=0,001 ml=1μl; 1-10 λ; y > 10 λ) y la composición de las partículas. Se realizó RMD previa y 24h después del procedimiento, recogiéndose la aparición de lesiones, número, tamaño y distribución. Se correlacionaron estadísticamente los datos anteriores y con variables demográficas, clínicas y del procedimiento. Resultados. Cincuenta y ocho pacientes (76,3%) presentaron sintomatología previa al procedimiento. El 64,5% de los filtros (49) presentó partículas, la mayoría menores de 1 λ (77,5%), predominando los agregados fibrinoplaquetarios, restos celulares y cristales de colesterol. Doce pacientes (15,8%) demostraron lesiones en la RMD post-ASC, sin relación con el contenido en los filtros. No se encontró correlación estadística entre la presencia de material en los filtros y otras variables. Conclusiones. La isquemia post-ASC no depende únicamente de la carga embolígena y su naturaleza. La menor prevalencia de lesiones post-ASC en nuestra serie en comparación con otras indica que la adecuada selección de pacientes y la experiencia minimizan la influencia negativa de algunas variables, como la edad, en su aparición (AU)

Objectives. To evaluate the relation between the material retrieved from distal filters after carotid angioplasty and stenting and the development of ischemic brain lesions in diffusion-weighted imaging (DWI). To determine the influence of demographic, clinical, and procedural variables in the pathogenesis of emboli and in ischemia after carotid angioplasty and stenting. Material and methods. We submitted the contents of the filters of 76 patients (60 men; mean age, 68.39years; range, 46-82) who had undergone angioplasty and stenting for severe stenosis of the internal carotid artery for histologic analysis evaluating volume (< 1 λ=0.001ml = 1μl; 1-10 λ; and > 10 λ) and the composition of the particles. All patients underwent DWI before and 24hours after the procedure; we recorded whether lesions appeared and their number, size, and distribution. We correlated the findings with demographic, clinical, and procedural variables. Results. Symptoms were present before the procedure in 58 (76.3%) patients. Particles were present in 49 (64.5%) of the filters; most particles (77.5%) were 1 λ with a predominance of fibrin-platelet aggregates, cell remnants, and cholesterol crystals. DWI after the procedure detected lesions in 12 (15.8%) patients. We found no statistically significant correlation between filter contents and lesion detection after the procedure or between filter contents and other variables. Conclusions. Ischemia after carotid angioplasty and stenting does not depend solely on the embolic load and its nature. We consider that the lower prevalence of postprocedural lesions in our series compared to others suggests that appropriate patient selection and experience minimize the negative influence of some variables like age in their development(AU)

The autoimmune disease-associated IL2RA locus is involved in the clinical manifestations of systemic sclerosis.

Regulatory T cells (T(regs)) are crucial in the maintenance of the immune tolerance and seem to have an important role in systemic sclerosis (SSc). The interleukin 2 receptor α (IL2RA) is an important T(reg) marker, and polymorphisms of IL2RA gene are associated with a number of autoimmune diseases. Therefore, we aimed to investigate for the first time the association of the IL2RA locus in SSc. For this purpose, a total of 3023 SSc patients and 2735 matched healthy controls, from six European Caucasian cohorts, were genotyped for the IL2RA gene variants rs11594656, rs2104286 and rs12722495 using the TaqMan allelic discrimination technology. The overall meta-analysis reached statistical significance when the three polymorphisms were tested for association with SSc, the limited subtype (lcSSc) and anti-centromere auto-antibodies (ACAs). However, no significant P-values were obtained when the ACA-positive patients were removed from the SSc and lcSSc groups, suggesting that these associations rely on ACA positivity. The strongest association signal with ACA production was detected for rs2104286 (P(FDR)=2.07 × 10(-4), odds ratio=1.30 (1.14-1.47)). The associations of rs11594656 and rs12722495 were lost after conditioning to rs2104286, and allelic combination tests did not evidence a combined effect, indicating that rs2104286 best described the association between IL2RA and ACA presence in SSc.

[Filter content after carotid angioplasty and stenting: relation to ischemic lesions in diffusion-weighted imaging]. / Contenido en filtros tras angioplastia y colocación de stent carotídeo: relación con lesiones isquémicas en la resonancia magnética de difusión.

OBJECTIVES: To evaluate the relation between the material retrieved from distal filters after carotid angioplasty and stenting and the development of ischemic brain lesions in diffusion-weighted imaging (DWI). To determine the influence of demographic, clinical, and procedural variables in the pathogenesis of emboli and in ischemia after carotid angioplasty and stenting. MATERIAL AND METHODS: We submitted the contents of the filters of 76 patients (60 men; mean age, 68.39 years; range, 46-82) who had undergone angioplasty and stenting for severe stenosis of the internal carotid artery for histologic analysis evaluating volume (< 1 λ = 0.001 ml = 1 µl; 1-10 λ; and > 10 λ) and the composition of the particles. All patients underwent DWI before and 24 hours after the procedure; we recorded whether lesions appeared and their number, size, and distribution. We correlated the findings with demographic, clinical, and procedural variables. RESULTS: Symptoms were present before the procedure in 58 (76.3%) patients. Particles were present in 49 (64.5%) of the filters; most particles (77.5%) were 1 λ with a predominance of fibrin-platelet aggregates, cell remnants, and cholesterol crystals. DWI after the procedure detected lesions in 12 (15.8%) patients. We found no statistically significant correlation between filter contents and lesion detection after the procedure or between filter contents and other variables. CONCLUSIONS: Ischemia after carotid angioplasty and stenting does not depend solely on the embolic load and its nature. We consider that the lower prevalence of postprocedural lesions in our series compared to others suggests that appropriate patient selection and experience minimize the negative influence of some variables like age in their development.

Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis.

OBJECTIVE: Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. METHODS: 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. RESULTS: The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p(FDRcorrected)=0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p(FDRcorrected)=0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p(FDRcorrected)=0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). CONCLUSION: The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.

BANK1 functional variants are associated with susceptibility to diffuse systemic sclerosis in Caucasians.

OBJECTIVE: To investigate the possible association of the BANK1 gene with genetic susceptibility to systemic sclerosis (SSc) and its subphenotypes. METHODS: A large multicentre case-control association study including 2380 patients with SSc and 3270 healthy controls from six independent case-control sets of Caucasian ancestry (American, Spanish, Dutch, German, Swedish and Italian) was conducted. Three putative functional BANK1 polymorphisms (rs17266594 T/C, rs10516487 G/A, rs3733197 G/A) were selected as genetic markers and genotyped by Taqman 5 allelic discrimination assay. RESULTS: A significant association of the rs10516487 G and rs17266594 T alleles with SSc susceptibility was observed (pooled OR=1.12, 95% CI 1.03 to 1.22; p=0.01 and pooled OR=1.14, 95% CI 1.05 to 1.25; p=0.003, respectively), whereas the rs3733197 genetic variant showed no statistically significant deviation. Stratification for cutaneous SSc phenotype showed that the BANK1 rs10516487 G, rs17266594 T and rs3733197 G alleles were strongly associated with susceptibility to diffuse SSc (dcSSc) (pooled OR=1.20, 95% CI 1.05 to 1.37, p=0.005; pooled OR=1.23, 95% CI 1.08 to 1.41, p=0.001; pooled OR=1.15, 95% CI 1.02 to 1.31, p=0.02, respectively). Similarly, stratification for specific SSc autoantibodies showed that the association of BANK1 rs10516487, rs17266594 and rs3733197 polymorphisms was restricted to the subgroup of patients carrying anti-topoisomerase I antibodies (pooled OR=1.20, 95% CI 1.02 to 1.41, p=0.03; pooled OR=1.24, 95% CI 1.05 to 1.46, p=0.01; pooled OR=1.26, 95% CI 1.07 to 1.47, p=0.004, respectively). CONCLUSION: The results suggest that the BANK1 gene confers susceptibility to SSc in general, and specifically to the dcSSc and anti-topoisomerase I antibody subsets.

[The role of ambulatory electroencephalogram monitoring: experience and results in 264 records]. / El papel diagnóstico del Holterelectroencefalograma ambulatorio: experiencia y resultados en 264 registros.

INTRODUCTION: Ambulatory electroencephalogram (EEG) monitoring allows for long-term, mobile electroencephalographic recordings of patients. This study aims to describe and analyze the results obtained with ambulatory EEG in our clinical practice. METHODS: We have analyzed the results of 264 ambulatory EEG records, grouped according to the reason for the request: a) group 1: diagnostic evaluation of episodes of epileptic nature; b) group 2: diagnostic evaluation of paroxysmal episodes, and c) group 3: evaluation of the risk of relapse during anti-seizure treatment withdrawal in certain epileptic patients. RESULTS: a) Group 1 (n=137): normal results were found in 54 records (39.4%). There was generalized epileptic activity in 20 (14.6%) of them (5 with ictal activity) and focal epileptic activity was detected in 57 cases (42%) (8 with ictal activity). No EEG diagnosis could be reached in 6 (4%) recordings due to the presence of artefacts; b) group 2 (n=99): in 47 records (47.5 %), there were no episodes and the Holter-EEG was normal. There was a clinically documented episode without anomalies during Holter-EEG registration in 14 cases (14.2%). In 29 records (29.3%), focal epileptic activity was recorded (ictal 4) and generalized epileptic activity (ictal in 1) was recorded in 4 patients (4%). No EEG diagnosis could be reached in 5 cases (5%), and c) group 3 (n=28): the study was normal in 15 cases (53.6%) and showed focal interictal epileptic activity in 8 (28.6 %) and generalized interictal epileptic activity in 5 of them (17.8%). CONCLUSION: We believe that the ambulatory EEG recordings in correctly selected cases can provide important additional information regarding global assessment of patients with epilepsy.

Clinical characteristics associated with psychosocial functioning among patients with uncomplicated epilepsy in Spain.

OBJECTIVE: To identify the clinical characteristics associated with poor psychosocial functioning among Spanish patients with epilepsy but no other neurological or psychiatric disorder. METHODS: Between May and September 2001 a survey among patients with epilepsy was carried out in 32 Spanish health care centres. The selection criteria of patients were attendance to a routine neurologist visit, to be aged between 25 and 64 and not having another additional neurological handicap (n=812). Psychosocial function was elicited through six indicators: educational level, marital status, unemployment status, restricted car driving, self-perception of epilepsy as an important limiting factor in the educational level achieved and, among unemployed, as the cause of their unemployment. Multiple logistic regression models were fitted in order to calculate adjusted odds ratios (aOR) and their 95% confidence intervals. RESULTS: After simultaneously adjusting for socio-demographic variables and clinical characteristics, the six outcomes analysed increased with seizure frequency. Moreover, all the outcomes except low educational level were also related to early age at onset of epilepsy. Although no relation with objective educational level was found, there was a strong association between early age at onset of symptoms and self-perception of epilepsy as an important limiting factor of educational achievement. CONCLUSION: These findings emphasize the need for more effective treatment of epilepsy and also highlight the importance of a psychosocial approach to management of epilepsy for patients with an early onset of symptoms in order to prevent social limitations in adult life.

[Noninvasive diagnosis of cerebral venous thrombosis]. / Diagnóstico de trombosis venosas cerebrales mediante técnicas no invasivas.

OBJECTIVES: Cerebral venous thrombosis (CVT) is an uncommon condition. Its variable, unspecific clinical presentation causes delays in diagnosis. We analyze the validity of different neuroimaging techniques, including CT, MRI, MR angiography, and conventional angiography in the diagnosis of CVT. MATERIAL AND METHODS: We review the imaging findings of 12 patients with the final diagnosis of CVT. All 12 patients underwent CT as the initial imaging test; all 12 underwent MRI; 11 underwent MR angiography; and 4 underwent conventional angiography. Visualization of the thrombus or filling defects in the affected vessel were considered direct signs of CVT, whereas findings compatible with venous infarction were considered indirect signs. RESULTS: Of the 12 CT examinations, 4 showed direct signs, 2 indirect signs, and 6 only normal findings. Indirect signs of CVT were seen on follow-up CT in three of the patients with normal initial CT examination. CT failed to show the real extent of the process except in one case in which a cortical vein was affected. MRI detected thrombi in the affected territory in 6 cases; the empty delta sign was seen in 2 and signs of venous infarction in 8. MRI failed to diagnose CVT in one case. MR angiography showed direct signs of CVT in all cases, even without intravenous contrast, and the results were similar to those seen at conventional angiography. More than two locations were affected in 11 patients. CONCLUSIONS: At CT, indirect signs of CVT are seen, although sometimes not immediately. Direct signs can be so subtle that they can only be interpreted with experience. Furthermore, CT does not show the real extent of the process. Nevertheless, given its availability, contrast-enhanced CT should be the primary imaging test, both to rule out other possibilities and to indicate other neuroimaging studies, in this case MRI and MR angiography. The results obtained when these two techniques are performed simultaneously, even without contrast administration, are sufficient for diagnosis and are comparable to those at conventional angiography, but without the risks entailed and without exposing the patient to ionizing radiation.

Diagnóstico de trombosis venosas cerebrales mediante técnicas no invasivas / Noninvasive diagnosis of cerebral venous thrombosis

Objetivos. La trombosis venosa cerebral (TVC) es una patología poco frecuente. Su presentación clínica es inespecífica y variable, lo que ocasiona retrasos en el diagnóstico. Analizamos la validez de las diferentes pruebas de neuroimagen, tomografía computarizada (TC), resonancia magnética (RM), angio-resonancia magnética (RMV) y angiografía, en el diagnóstico de TVC. Material y métodos. Estudio retrospectivo sobre 12 pacientes con diagnóstico final de TVC. Se realizó TC, que fue la prueba inicial, y RM a todos los pacientes, a 11 RMV y en 4 ocasiones se hizo angiografía. Se valoraron como signos directos la visualización del trombo o defectos de repleción en el vaso afecto y como signo indirecto la identificación de hallazgos compatibles con infarto venoso. Resultados. De las 12 TC, 4 mostraron signos directos, 2 indirectos y 6 fueron normales; de éstas, en 3 pacientes se objetivaron signos indirectos en TC evolutivos. No mostró la extensión real del proceso salvo en un caso de afectación localizada de una vena cortical. En la RM se objetivó ocupación de los vasos del territorio venosos afecto en 6 casos, en 2 se apreció el signo del delta vacío y en 8 signos de infarto venoso. En una ocasión no fue diagnóstica. En todas las RMV se visualizaron signos directos de TVC, incluso sin contraste intravenoso. Los resultados fueron similares a los de las angiografías. Once pacientes presentaban afectación de más de 2 localizaciones. Conclusiones. La TC pone de manifiesto signos indirectos, a veces de modo tardío, y signos directos tan sutiles que requieren experiencia para ser interpretados. Además no valora la extensión real del proceso. De todos modos debe utilizarse como técnica de primer nivel, con contraste intravenoso, dada su disponibilidad en la mayoría de los centros, para excluir otras causas y servir para la indicación de otras pruebas de neuroimagen, en este caso RM y RMV. Los resultados obtenidos con la realización simultánea de ambas son equiparables a los de la angiografía, evita los riesgos de esta técnica, no expone al paciente a radiaciones ionizantes y es diagnóstica incluso sin la administración de contraste

Objectives. Cerebral venous thrombosis (CVT) is an uncommon condition. Its variable, unspecific clinical presentation causes delays in diagnosis. We analyze the validity of different neuroimaging techniques, including CT, MRI, MR angiography, and conventional angiography in the diagnosis of CVT. Material and methods. We review the imaging findings of 12 patients with the final diagnosis of CVT. All 12 patients underwent CT as the initial imaging test; all 12 underwent MRI; 11 underwent MR angiography; and 4 underwent conventional angiography. Visualization of the thrombus or filling defects in the affected vessel were considered direct signs of CVT, whereas findings compatible with venous infarction were considered indirect signs. Results. Of the 12 CT examinations, 4 showed direct signs, 2 indirect signs, and 6 only normal findings. Indirect signs of CVT were seen on follow-up CT in three of the patients with normal initial CT examination. CT failed to show the real extent of the process except in one case in which a cortical vein was affected. MRI detected thrombi in the affected territory in 6 cases; the empty delta sign was seen in 2 and signs of venous infarction in 8. MRI failed to diagnose CVT in one case. MR angiography showed direct signs of CVT in all cases, even without intravenous contrast, and the results were similar to those seen at conventional angiography. More than two locations were affected in 11 patients. Conclusions. At CT, indirect signs of CVT are seen, although sometimes not immediately. Direct signs can be so subtle that they can only be interpreted with experience. Furthermore, CT does not show the real extent of the process. Nevertheless, given its availability, contrast-enhanced CT should be the primary imaging test, both to rule out other possibilities and to indicate other neuroimaging studies, in this case MRI and MR angiography. The results obtained when these two techniques are performed simultaneously, even without contrast administration, are sufficient for diagnosis and are comparable to those at conventional angiography, but without the risks entailed and without exposing the patient to ionizing radiation

[Classic antiepileptic and new generation antiepileptic drugs: gender differences in effectiveness and adverse drug reactions]. / Fármacos antiepilépticos clásicos y de nueva generación: diferencias de sexo en la efectividad y en las reacciones adversas.

INTRODUCTION: Women are more likely to suffer adverse drug reactions. Moreover adverse drug reactions differ depending on gender. The main objective of new generation antiepileptic drugs (AED) is to reduce adverse drug reactions while maintaining the same effectiveness as the classic ones. OBJECTIVES: a) To identify sociodemographic and clinical variables associated with being treated with new generation AEDs, and b) to compare effectiveness, averse drug reactions and quality of life among patients treated with monotherapy, either with classic or with new generation AEDs, examining the potential gender differences. PATIENTS AND METHODS: A survey among 990 patients aged 16-64 with epilepsy was carried out in 32 Spanish hospitals (response rate: 96 %). For the purposes of this study patients treated with monotherapy (n = 496) were selected. The outcome variables were: effectiveness in seizure control, adverse drug reactions and three dimensions of the SF-36 questionnaire (vitality, mental health and self-perceived health status). RESULTS: 21 % of women and 8% of men were treated with new AEDs. Women were more likely to be treated with new generation AEDs. Moreover, age of epilepsy onset was also positively related to new AEDs and a gradient was found. Whereas no differences in effectiveness, adverse drug reactions or quality of life were observed among men, among women, those treated with new generation AEDs had less adverse drug reactions but, on the other hand, effectiveness for controlling seizures was lower. CONCLUSIONS: Women are more likely to be treated with new AEDs. Although these new treatments seem to have less adverse drug reactions among females, their effectiveness in controlling seizures are lower than that of classic AEDs.

Mutation analysis in 16 patients with mtDNA depletion.

Sixteen unrelated Southern European patients with the mitochondrial depletion syndrome (MDS) were analyzed for mutations in the TK2 and DGUOK genes. Three novel mutations were identified in TK2 (R183G, R254X, and 142insG). When we analyzed additional genes involved in the dNTPs pool, such as SLC25A19 (DNC) and NT5M (d-NT2), we did not detect mutations. The current study suggest that scanning the TK2, DGUOK, SLC25A19, and NT5M genes is likely to help about 10% of MDS families in terms of genetic counseling. Also, our findings indicate that genotype-phenotype correlations are not straightforward in MDS.

[Periodic lateralised epileptiform discharges as a form of presentation of neurosyphilis]. / Descargas epileptiformes lateralizadas y periódicas como forma de presentación de neurosífilis.

INTRODUCTION: Neurosyphilis is a recognised cause of epileptic seizures, but its association with periodic lateralised epileptiform discharges (PLED) has been described only rarely, in spite of the fact that it gives rise to acute vascular lesions. CLINICAL CASE: We report the case of a male patient who was diagnosed as having meningovascular syphilis after the onset of tonic clonic epileptic seizures and PLED in the left frontotemporal region. The initial neurological exploration revealed a syndrome of confusion and mild mixed, but predominantly motor, dysphasia. In complementary tests, the most noteworthy features were positive luetic serology in the blood and in cerebrospinal fluid (CSF), which was confirmed by means of treponemic assays. The patient was treated with penicillin for two weeks. The study was completed with a magnetic resonance (MR) brain scan that showed a small left temporal infarction, which was the origin of the clinical and electrical convulsive activity. The patient s evolution was satisfactory, with an improvement in the language disorder, and the seizures were controlled after the administration of phenytoin. The control electroencephalogram (EEG) that was performed later only showed a slowing in the known injured area. CONCLUSIONS: PLED are an infrequent electroencephalographic pattern whose appearance has been linked with acute brain lesions, mainly with strokes, tumours and meningoencephalitis. When, exceptionally, they appear as a consequence of an ischemia secondary to meningovascular syphilis their significance, clinical features and prognosis do not differ from other causes of a cerebrovascular disease.

Influence of amino-terminal structures on kinetic transitions between several closed and open states in human erg K+ channels.

Gating kinetics of human ether-a-go-go (eag)-related gene (HERG) K+ channel expressed in Xenopus oocytes was studied using non-inactivating channel variants carrying different structural modifications in the amino terminus. A kinetics model was elaborated to describe the behavior of full-length channels, that includes at least three open states besides the three closed states previously proposed. Deletion of the HERG-specific proximal domain (HERG D138-373) accelerated all individual forward transitions between closed states. Whereas relatively large amplitude depolarizations were required to drive full-length HERG channels to more distal open states, these were reached more easily in channels without proximal domain. Alteration of the initial eag/PAS domain by introduction of a short amino-acid sequence at the beginning of the amino terminus did not alter transitions between closed states, but prevented the channels from reaching the farthest open states that determine slower deactivation rates. This indicates that the presence of specific amino-terminal structures can be correlated with the occurrence of distinctive molecular transitions. It also demonstrates that both proximal and eag/PAS domains in the amino terminus contribute to set the gating characteristics of HERG channels.

Correlation between electrical activity and intracellular Ca2+ oscillations in GH3 rat anterior pituitary cells.

Simultaneous measurements of electrical activity and intracellular Ca(2+) levels were performed in perforated-patch current-clamped individual GH3 cells. Both in cells showing brief (<100 ms) and long action potentials (APs), we found a good correlation between the averaged intracellular Ca2+ concentration ([Ca2+]i) and AP frequency, but not between the mean [Ca2+]i and AP duration. Nevertheless, the magnitude of spontaneous Ca2+ oscillations was highly dependent on the size and duration of the APs. The decay of the Ca2+ transients was not slowed when the size of the oscillations was varied either spontaneously or after elongation of the AP with the K+ channel blocker tetraethyl ammonium. Furthermore, the recovery from Ca2+ loads similar to those induced by the APs was slightly retarded after treatment of the cells with intracellular store Ca2+-ATPase inhibitors. Among previous results showing that caffeine-induced [Ca2+]i increases are secondary to electrical activity enhancements in GH3 cells, these data indicate that the Ca2+ entry triggered via APs is the primary determinant of the [Ca2+]i variations, and that Ca2+-induced Ca2+ release has a minor contribution to Ca2+ oscillations recorded during spontaneous activity. They also point to modulation of electrical activity patterns as a crucial factor regulating spontaneous [Ca2+]i signalling, and hence pituitary cell functions in response to physiological secretagogues.

[Nonconvulsive status epilepticus: experience in 33 patients]. / Status epiléptico no convulsivo: experiencia en 33 pacientes.

BACKGROUND: To review the nonconvulsive status epilepticus diagnosed in a general hospital in order to identify its frequency, electroclinical characteristics and response to medical treatment. PATIENTS ANTS AND METHODS: A retrospective study of 33 cases of nonconvulsive status epilepticus was undertaken. The diagnosis was based on clinical and EEG manifestations. Data regarding their clinical presentation, previous epilepsy, etiology of the status, its medical management and outcome were analysed. RESULTS: The 33 patients comprising the study included 20 men and 13 women. The medium age was 49.8 years. A previous history of epilepsy was present in 51.5% of them. Most of the patients presented impaired consciousness (39.4%) or confusional state (36%). The mean duration of the disorder did not exceed 24 hours (64.5%). There were five cases of absence status and 28 of complex partial status, two of them with secondary generalization. A precipitating factor was found in 80% of the patients and the cerebrovascular etiology was the most frequent. There was a good response to phenytoin (80%), although in the first month death was the final outcome for 25% of them. CONCLUSIONS: Nonconvulsive status epilepticus is an underdiagnosed medical emergency because of its different manifestations, similar to confusional or psyquiatric states. The precipitating factor determines its outcome. A high index of suspicion is needed in order to make a faster diagnosis and treatment.