[Rapidly progressive intracranial large artery aterosclerosis, a rare stroke etiology]. / Arterioesclerosis intracraneal rápidamente progresiva, una rara etiología de ictus.

INTRODUCTION: Intracranial atheromatosis is one of the most frequent causes of stroke. It is usually a slowly progressive process and normally associated with the sum of vascular risk factors. CASE REPORT: In this case we present a rapidly progressive development of intracranial atheromatosis demonstrated by serial neuroimaging techniques and sample analysis in a 72-year-old female patient with high levels of interleukin-6 and C-reactive protein, with no signs of vasculitis. CONCLUSION: Rapidly progressive intracranial atheromatosis should be considered in adult patients over 50 years of age with recurrent stroke.

TITLE: Arterioesclerosis intracraneal rápidamente progresiva, una rara etiología de ictus.Introducción. La ateromatosis intracraneal es una de las causas más frecuentes de ictus. Suele ser un proceso lentamente progresivo y normalmente asociado a la suma de factores de riesgo vascular. Caso clínico. En este caso presentamos una evolución rápidamente progresiva de la ateromatosis intracraneal demostrada por técnicas de neuroimagen seriadas y análisis de la muestra en una paciente de 72 años con niveles altos de interleucina-6 y proteína C reactiva, sin signos de vasculitis. Conclusión. La ateromatosis intracraneal rápidamente progresiva se debe tener en cuenta en pacientes adultos mayores de 50 años con ictus de repetición.

Arterioesclerosis intracraneal rápidamente progresiva, una rara etiología de ictus / Rapidly progressive intracranial large artery aterosclerosis, a rare stroke etiology

Introducción: La ateromatosis intracraneal es una de las causas más frecuentes de ictus. Suele ser un proceso lentamente progresivo y normalmente asociado a la suma de factores de riesgo vascular. Caso clínico: En este caso presentamos una evolución rápidamente progresiva de la ateromatosis intracraneal demostrada por técnicas de neuroimagen seriadas y análisis de la muestra en una paciente de 72 años con niveles altos de interleucina-6 y proteína C reactiva, sin signos de vasculitis. Conclusión: La ateromatosis intracraneal rápidamente progresiva se debe tener en cuenta en pacientes adultos mayores de 50 años con ictus de repetición.(AU)

Introduction: Intracranial atheromatosis is one of the most frequent causes of stroke. It is usually a slowly progressive process and normally associated with the sum of vascular risk factors. Case report: In this case we present a rapidly progressive development of intracranial atheromatosis demonstrated by serial neuroimaging techniques and sample analysis in a 72-year-old female patient with high levels of interleukin-6 and C-reactive protein, with no signs of vasculitis. Conclusion: Rapidly progressive intracranial atheromatosis should be considered in adult patients over 50 years of age with recurrent stroke.(AU)

Debilidad como complicación del paciente crítico por COVID-19: características clínicas y factores pronósticos en una serie de casos / Weakness as a complication of COVID-19 in critically ill patients: clinical features and prognostic factors in a case series

Introducción: La debilidad es una complicación frecuente en el enfermo crítico por COVID-19. Se describen sus características, y los factores que pueden condicionarla y predecirla. Pacientes y métodos: Estudio observacional descriptivo prospectivo con pacientes ingresados en la unidad de cuidados intensivos (UCI) por COVID-19 entre abril y mayo de 2020 con debilidad muscular. Se consideró una afectación clínica grave un equilibrio motor igual o inferior a 3/5 según la escala de fuerza muscular modificada del Medical Research Council. Se han realizado 25 estudios analíticos, 16 estudios neurofisiológicos y una biopsia muscular; seguimiento telefónico al mes; análisis comparativo entre los grupos con y sin afectación grave, y determinación de puntos de corte de parámetros analíticos para predecir afectación grave mediante curvas ROC. Resultados: Se incluyó a 25 pacientes con 58 años (desviación estándar ± 9) de edad media. La mediana de estancia en la UCI fue de 27,5 días. Todos los electromiogramas mostraban un patrón miógeno y el 75%, también una neuropatía. El grupo con afectación clínica grave tenía mayores niveles de dímero-D (p = 0,08), lactato deshidrogenasa (p = 0,03) e interleucina 6 (p = 0,10), y la combinación de la alteración de dos cualquiera de estos tres parámetros pronosticaba la afectación grave con una sensibilidad del 100% y una especificidad del 76,9%. Al mes de seguimiento, el 36% no podía deambular autónomamente y el 92% seguía con debilidad muscular. Conclusiones: La debilidad en el enfermo por COVID-19 grave tiene una repercusión clínica importante. Su detección y estudio precoces mediante predictores de su desarrollo pueden permitir un mejor manejo. La ausencia en algunos casos de los factores de riesgo clásicos para la debilidad adquirida en la UCI sugiere una fisiopatología diferente.(AU)

Introduction: Weakness is a frequent complication in those critically ill due to COVID-19. This study describes its characteristics and the factors that can condition and predict it. Patients and methods: We conducted a prospective, descriptive, observational study of patients admitted to the intensive care unit (ICU) due to COVID-19 between April and May 2020 with muscle weakness. A motor balance equal to or lower than 3/5 according to the modified Medical Research Council muscle strength scale was considered to be severe clinical impairment. Altogether 25 analytical studies, 16 neurophysiological studies and one muscle biopsy were performed, with a telephone follow-up at one month, a comparative analysis between the groups with and without severe compromise, and determination of cut-off points for analytical parameters to predict severe involvement using ROC curves. Results: The sample consisted of 25 patients with a mean age of 58 years (standard deviation ± 9). The median length of stay in the ICU was 27.5 days. All the electromyograms exhibited a myogenic pattern and 75% also showed neuropathy. The group with severe clinical involvement had higher levels of D-dimer (p = 0.08), lactate dehydrogenase (p = 0.03) and interleukin-6 (p = 0.10), and the combination of the alteration of any two of these three parameters predicted severe involvement with a sensitivity of 100% and a specificity of 76.9%. At one month of follow-up, 36% were unable to walk autonomously and 92% continued with muscle weakness. Conclusions: Weakness in severe COVID-19 patients has a major clinical impact. Its early detection and study by means of predictors of its development may allow for better management. The absence in some cases of classical risk factors for ICU-acquired weakness suggests a different pathophysiology.(AU)

[Weakness as a complication of COVID-19 in critically ill patients: clinical features and prognostic factors in a case series]. / Debilidad como complicación del paciente crítico por COVID-19: características clínicas y factores pronósticos en una serie de casos.

INTRODUCTION: Weakness is a frequent complication in those critically ill due to COVID-19. This study describes its characteristics and the factors that can condition and predict it. PATIENTS AND METHODS: We conducted a prospective, descriptive, observational study of patients admitted to the intensive care unit (ICU) due to COVID-19 between April and May 2020 with muscle weakness. A motor balance equal to or lower than 3/5 according to the modified Medical Research Council muscle strength scale was considered to be severe clinical impairment. Altogether 25 analytical studies, 16 neurophysiological studies and one muscle biopsy were performed, with a telephone follow-up at one month, a comparative analysis between the groups with and without severe compromise, and determination of cut-off points for analytical parameters to predict severe involvement using ROC curves. RESULTS: The sample consisted of 25 patients with a mean age of 58 years (standard deviation ± 9). The median length of stay in the ICU was 27.5 days. All the electromyograms exhibited a myogenic pattern and 75% also showed neuropathy. The group with severe clinical involvement had higher levels of D-dimer (p = 0.08), lactate dehydrogenase (p = 0.03) and interleukin-6 (p = 0.10), and the combination of the alteration of any two of these three parameters predicted severe involvement with a sensitivity of 100% and a specificity of 76.9%. At one month of follow-up, 36% were unable to walk autonomously and 92% continued with muscle weakness. CONCLUSIONS: Weakness in severe COVID-19 patients has a major clinical impact. Its early detection and study by means of predictors of its development may allow for better management. The absence in some cases of classical risk factors for ICU-acquired weakness suggests a different pathophysiology.

TITLE: Debilidad como complicación del paciente crítico por COVID-19: características clínicas y factores pronósticos en una serie de casos.Introducción. La debilidad es una complicación frecuente en el enfermo crítico por COVID-19. Se describen sus características, y los factores que pueden condicionarla y predecirla. Pacientes y métodos. Estudio observacional descriptivo prospectivo con pacientes ingresados en la unidad de cuidados intensivos (UCI) por COVID-19 entre abril y mayo de 2020 con debilidad muscular. Se consideró una afectación clínica grave un equilibrio motor igual o inferior a 3/5 según la escala de fuerza muscular modificada del Medical Research Council. Se han realizado 25 estudios analíticos, 16 estudios neurofisiológicos y una biopsia muscular; seguimiento telefónico al mes; análisis comparativo entre los grupos con y sin afectación grave, y determinación de puntos de corte de parámetros analíticos para predecir afectación grave mediante curvas ROC. Resultados. Se incluyó a 25 pacientes con 58 años (desviación estándar ± 9) de edad media. La mediana de estancia en la UCI fue de 27,5 días. Todos los electromiogramas mostraban un patrón miógeno y el 75%, también una neuropatía. El grupo con afectación clínica grave tenía mayores niveles de dímero-D (p = 0,08), lactato deshidrogenasa (p = 0,03) e interleucina 6 (p = 0,10), y la combinación de la alteración de dos cualquiera de estos tres parámetros pronosticaba la afectación grave con una sensibilidad del 100% y una especificidad del 76,9%. Al mes de seguimiento, el 36% no podía deambular autónomamente y el 92% seguía con debilidad muscular. Conclusiones. La debilidad en el enfermo por COVID-19 grave tiene una repercusión clínica importante. Su detección y estudio precoces mediante predictores de su desarrollo pueden permitir un mejor manejo. La ausencia en algunos casos de los factores de riesgo clásicos para la debilidad adquirida en la UCI sugiere una fisiopatología diferente.

CCL23: a new CC chemokine involved in human brain damage.

BACKGROUND: CCL23 role in the inflammatory response after acute brain injuries remains elusive. Here, we evaluated whether CCL23 blood levels associate with acquired cerebral lesions and determined CCL23 predictive capacity for assessing stroke prognosis. We used preclinical models to study the CCL23 homologous chemokines in rodents, CCL9 and CCL6. METHODS: Baseline CCL23 blood levels were determined on 245 individuals, including ischaemic strokes (IS), stroke mimics and controls. Temporal profile of circulating CCL23 was explored from baseline to 24 h in 20 of the IS. In an independent cohort of 120 IS with a 3-month follow-up, CCL23 blood levels were included in logistic regression models to predict IS outcome. CCL9/CCL6 cerebral expression was evaluated in rodent models of brain damage. Both chemokines were also profiled in circulation and histologically located on brain following ischaemia. RESULTS: Baseline CCL23 blood levels did not discriminate IS, but permitted an accurate discrimination of patients presenting acute brain lesions (P = 0.003). IS exhibited a continuous increase from baseline to 24 h in circulating CCL23 (P < 0.001). Baseline CCL23 blood levels resulted an independent predictor of IS outcome at hospital discharge (ORadj : 19.702 [1.815-213.918], P = 0.014) and mortality after 3 months (ORadj : 21.47 [3.434-134.221], P = 0.001). In preclinics, expression of rodent chemokines in neurons following cerebral lesions was elevated. CCL9 circulating levels decreased early after ischaemia (P < 0.001), whereas CCL6 did not alter within the first 24 h after ischaemia. CONCLUSIONS: Although preclinical models do not seem suitable to characterize CCL23, it might be a novel promising biomarker for the early diagnosis of cerebral lesions and might facilitate the prediction of stroke patient outcome.

Outcome of cancer-related seizures in patients treated with lacosamide.

OBJECTIVES: Lacosamide is an antiepileptic drug (AED), which has proven to be effective to control seizures, including acute conditions such as status epilepticus. The aim of this study is to describe the clinical experience with lacosamide in neuro-oncological patients. MATERIALS AND METHODS: Multicenter retrospective study in patients with cancer-related seizures, who received lacosamide as an add-on therapy. RESULTS: Forty-eight patients with benign and malignant tumors, including primary brain tumors, lymphomas, systemic cancer with central nervous system involvement, or paraneoplastic encephalitis, were included. Lacosamide was effective in the control of chronic seizures in patients with either benign or malignant tumors. The success rate was greater in malignant tumors, and drug-resistant epilepsies were more likely associated with benign tumors. Adverse events occurred in nearly 70% of patients, particularly in acute conditions and associated with the concomitant use of radio-/chemotherapy. Lacosamide-related adverse events were more likely somnolence and dizziness, which usually resolved after dose adjustment. After starting lacosamide, nearly half of the patients discontinued one of the baseline AEDs and decreased or discontinued dexamethasone. Fifteen patients with status epilepticus were treated with intravenous lacosamide, and 73% of them had their condition resolved without serious drug-related adverse events. CONCLUSION: Lacosamide is an AED to consider in cases of cancer-related seizures. Lacosamide pharmacodynamics and pharmacokinetics allow the achievement of responder rates over 50% with no serious adverse effects, amelioration of side effects from other AEDs or radio-/chemotherapy, and no significant drug interactions. Furthermore, the intravenous formulation shows clear benefits in acute conditions such as status epilepticus.

[Atypical ganglioglioma with BRAF V600E mutation: a case report and review of the literature]. / Ganglioglioma atipico con mutacion de BRAF V600E: caso clinico y revision de la bibliografia.

INTRODUCTION: Gangliogliomas are rare tumours that affect young patients, appear predominantly in the temporal lobe and usually begin with epileptic seizures. Histologically they have a grade I of malignancy, with an anaplastic form that is catalogued as grade III in the 2007 WHO classification. Yet, there are tumours that do not meet the criteria of either grade and which offer clear prognostic differences with respect to those of grade I. These tumours would be atypical gangliogliomas (grade II), which are not considered in this classification. From the molecular point of view, the best known alteration in gangliogliomas is the BRAF V600E mutation, which worsens the prognosis of the lesion. The possible use of treatments targeted towards this mutated protein is especially relevant in this disorder. CASE REPORT: A 21-year-old male, who had undergone surgery due to a ganglioglioma on two occasions. The neuro-pathological examination revealed histological features consistent with an intermediate grade of malignancy (grade II), with positive BRAF mutation. CONCLUSIONS: The case presented here, together with those previously reported in the literature, reopens the debate on the definition of gangliogliomas in the 2007 WHO classification, and lends support to the fact that the next classification should again include atypical gangliogliomas (grade II), together with possible genetic mutations and molecular disorders.

TITLE: Ganglioglioma atipico con mutacion de BRAF V600E: caso clinico y revision de la bibliografia.Introduccion. Los gangliogliomas son tumores raros que afectan a pacientes jovenes, aparecen predominantemente en el lobulo temporal y suelen comenzar con crisis epilepticas. Histologicamente corresponden a un grado I de malignidad, con una forma anaplasica catalogada como de grado III en la clasificacion de la Organizacion Mundial de la Salud (OMS) de 2007. Sin embargo, existen tumores que no cumplen criterios de uno u otro grado y que presentan claras diferencias pronosticas respecto a los de grado I. Estos tumores corresponderian a gangliogliomas atipicos (grado II), no contemplados en la citada clasificacion. Desde el punto de vista molecular, la alteracion mas conocida en los gangliogliomas es la mutacion de BRAF V600E, que confiere peor pronostico a la lesion. La posibilidad de utilizar tratamientos dirigidos a esta proteina mutada otorga una especial relevancia a esta alteracion. Caso clinico. Varon de 21 años, intervenido de un ganglioglioma en dos ocasiones, en el que el examen neuropatologico objetivo caracteristicas histologicas compatibles con un grado de malignidad intermedio (grado II) con mutacion positiva a BRAF. Conclusiones. El caso presentado, junto con los descritos previamente en la bibliografia, reabre las controversias sobre la definicion de los gangliogliomas en la clasificacion de la OMS de 2007, y apoya el hecho de que la proxima clasificacion de la OMS deberia volver a incluir los gangliogliomas atipicos (grado II) e integrar posibles mutaciones geneticas y alteraciones moleculares.

Expression of semaphorin 3A, semaphorin 7A and their receptors in multiple sclerosis lesions.

BACKGROUND: Studies in multiple sclerosis (MS) and in experimental models point to a critical role of semaphorin (sema)3A and sema7A in MS pathogenesis. OBJECTIVE: The objective of this paper is to characterise the expression of sema3A, sema7A, and their receptors in MS lesions. METHODS: We included 44 demyelinating lesions from MS patients, 12 lesions with acute cerebral infarct, 11 lesions with progressive multifocal leucoencephalopathy and 10 non-neurological control patients. MS lesions were classified according to inflammatory activity and all samples were immunostained for sema3A, sema7A, neuropilin 1 (Np-1), α1-integrin, and ß1-integrin. RESULTS: In MS-damaged white matter sema3A and Np-1 were both detected in microglia/macrophages, whereas reactive astrocytes expressed only sema3A. Otherwise, sema7A, α1-integrin and ß1-integrin were observed in reactive astrocytes, and microglia/macrophages only expressed ß1-integrin. The expression of sema3A, sema7A and their receptors is more relevant in MS than in other demyelinating diseases. Sema3A and sema7A expression correlated with the inflammatory activity of the MS lesions, suggesting their involvement in the immunological process that takes place in MS. CONCLUSIONS: The expression pattern of sema3A, sema7A and their receptors in MS lesions suggests that both molecules contribute to create a negative environment for tissue regeneration, influencing the ability to regenerate the damaged tissue.

Pixel-by-Pixel Comparison of Volume Transfer Constant and Estimates of Cerebral Blood Volume from Dynamic Contrast-Enhanced and Dynamic Susceptibility Contrast-Enhanced MR Imaging in High-Grade Gliomas.

BACKGROUND AND PURPOSE: Estimates of blood volume and volume transfer constant are parameters commonly used to characterize hemodynamic properties of brain lesions. The purposes of this study were to compare values of volume transfer constant and estimates of blood volume in high-grade gliomas on a pixel-by-pixel basis to comprehend whether they provide different information and to compare estimates of blood volume obtained by dynamic contrast-enhanced MR imaging and dynamic susceptibility contrast-enhanced MR imaging. MATERIALS AND METHODS: Thirty-two patients with biopsy-proved grade IV gliomas underwent dynamic contrast-enhanced MR imaging and dynamic susceptibility contrast-enhanced MR imaging, and parametric maps of volume transfer constant, plasma volume, and CBV maps were calculated. The Spearman rank correlation coefficients among matching values of CBV, volume transfer constant, and plasma volume were calculated on a pixel-by-pixel basis. Comparison of median values of normalized CBV and plasma volume was performed. RESULTS: Weak-but-significant correlation (P < .001) was noted for all comparisons. Spearman rank correlation coefficients were as follows: volume transfer constant versus CBV, ρ = 0.113; volume transfer constant versus plasma volume, ρ = 0.256; CBV versus plasma volume, ρ = 0.382. We found a statistically significant difference (P < .001) for the estimates of blood volume obtained by using dynamic contrast-enhanced MR imaging (mean normalized plasma volume, 13.89 ± 11.25) and dynamic susceptibility contrast-enhanced MR imaging (mean normalized CBV, 4.37 ± 4.04). CONCLUSIONS: The finding of a very weak correlation between estimates of microvascular density and volume transfer constant suggests that they provide different information. Estimates of blood volume obtained by using dynamic contrast-enhanced MR imaging are significantly higher than those obtained by dynamic susceptibility contrast-enhanced MR imaging in human gliomas, most likely due to the effect of contrast leakage.

Hirano body-rich subtypes of Creutzfeldt-Jakob disease.

BACKGROUND: In definite Creutzfeldt-Jakob disease (CJD), morphological and immunohistochemical patterns are useful to identify molecular subtypes. Severe cerebellar pathology and hippocampal involvement helps to identify VV subtypes. The rare VV1 variant (<1%), more frequent in young individuals, is additionally characterized by the presence of ballooned neurones in affected areas. In 1985, Cartier et al. described a family cluster of three individuals with an ataxic CJD form, showing, in addition to severe cerebellar and hippocampal involvement, the presence of frequent Hirano bodies (HB) in CA1 pyramidal neurones. HB are frequently found in aged individuals with Alzheimer pathology although they are not a specific finding. AIMS AND METHODS: In this study, we evaluated the presence of HB in hippocampi of 54 genetically and molecularly characterized CJD cases, aiming to elucidate whether additional morphological features could be helpful to point to molecular subtypes. RESULTS: We identified nine cases (four VV1, one out of three MV2K, three out of six MV2K+2C and one MV carrying a 96-base pair insertion) with abundant, partly bizarre and clustered HB in CA1 sector, not observed in other subtypes. The presence of HB was independent of hippocampal involvement by the disease itself. CONCLUSIONS: Clusters of abundant HB might be found in rare CJD subtypes such as VV1, MV2K/MV2K+2C and some genetic cases. In addition to histopathological and PrP immunohistochemical deposition patterns, their presence might be a useful additional morphologic feature that could point to the molecular subtype, especially when genetic and/or Western blot analyses are not available.

Cistoadenocarcinoma mucinoso de mama. A propósito de 2 casos y revisión de la literatura / No disponible

Objetivo: Los carcinomas productores de mucina constituyenuna entidad poco frecuente dentro de las neoplasias primariasde mama, siendo el carcinoma mucinoso (o coloide) elmás frecuente (2% del total de carcinomas mamarios). Dentrode este grupo, el cistoadenocarcinoma mucinoso es una entidadexcepcional de la que se han publicado 8 casos. Se tratade lesiones de pronóstico favorable que deben ser diferenciadasde otras lesiones mucoproductoras de mama, así como demetástasis de cistoadenocarcinomas de otras localizaciones.Casos clínicos: Presentamos dos nuevos casos de dos mujeresde 79 y 69 años que fueron biopsiadas y posteriormenteintervenidas en nuestro centro.Histológicamente el cistoadenocarcinoma mucinoso demama se presenta como una tumoración constituida por glándulasirregulares dilatadas revestidas por un epitelio cilíndrico,con abundante contenido mucinoso tanto en su interior comoextravasado y frecuente componente ductal in situ circundante,lo que permite diferenciarlos de otras lesiones mucoproductoras.Desde el punto de vista inmunohistoquímico suelenser negativos para HER2, p53 y receptores hormonales ymuestran expresión intensa y difusa de CK7 y ausencia deCK20, lo que facilita el diagnóstico diferencial con lesionesmetastáticas de otras localizaciones.Conclusiones: A pesar de su rareza, el cistoadenocarcinomamucinoso de mama es una neoplasia de buen pronóstico(sólo se han publicado 2 casos con afectación ganglionar yninguna muerte por enfermedad). Es importante tenerlo encuenta en el diagnóstico diferencial de lesiones mamarias mucinosastanto primarias como metastáticas, especialmenteante material escaso, como es el caso en las PBAG(AU)

Objective: Mucin producer carcinomas of the breast arequite unusual among primary breast tumors, being mucinouscarcinoma (colloid carcinoma) the most frequent (2% of allmammary carcinomas), In this group, mucinous cystadenocarcinomais an exceptional neoplasia with only 8 cases reported.Because of its favorable outcome, it must be differentiatedfrom other mucin producers lesions of the breast as well asfrom metastatic cystadenocarcinomas of other locations.Case reports: We present two new cases, a 79 and 69-years old women who underwent a core biopsy and a lumpectomyin our institution.Mammary mucinous cystadenocarcinomas appear as irregularexpanded glands with tall epithelium and abundant mucinintra and extracellular and foci of DCIS, which helps to differentiatethem from other mucin producers lesions of the breast.Immunohistochemical studies reveal an absence of HER2,p53, hormonal receptors and CK20 but an intense and diffuseexpression of CK7, which facilitates the differential diagnosiswith metastatic neoplasms.Conclusions: Even if mucinous cystadenocarcinoma of thebreast is a very unusual entity, it is a neoplasia with a goodoutcome (only 2 cases with lymph node involvement and nodeath by disease have been published). It is important to haveit in mind, especially when the material is poor (e.g. core biopsyspecimens)(AU)