Trombosis venosas cerebrales en la edad pediátrica: presentación clínica, factores de riesgo, diagnóstico y tratamiento

Introducción: Desde su primera descripción a mediados del siglo xix, mucho se ha avanzado en el conocimiento de esta entidad, que constituye una reconocida, aunque desestimada, causa de ictus en la infancia. Objetivo: Analizar la presentación clínica, factores de riesgo, evolución y tratamiento de una población de niños con trombosis venosa cerebral. Pacientes y métodos: Se llevó a cabo un estudio descriptivo, retrospectivo y longitudinal, de niños entre 0 y 17 años con trombosis venosa cerebral, en un período de cinco años. Resultados: Se identificaron 31 casos, de los cuales 18 fueron varones. Dieciocho pacientes comenzaron con convulsiones y 13 con síndrome de hipertensión endocraneal. Se identificaron 23 pacientes con procesos infecciosos, cuatro con patología de base previa, cinco con factores protrombóticos, tres neonatos con traumatismo obstétrico, cinco con más de un factor de riesgo y uno sin marcadores de riesgo. Se realizó diagnóstico por resonancia magnética en 18 pacientes, por tomografía computarizada con contraste en 11 y por angiorresonancia en los dos restantes. Dieciséis presentaron trombosis del seno transverso, cuatro del longitudinal superior, cuatro del sigmoides, cinco afectación de más de un seno y dos del seno cavernoso. Se inició anticoagulación en 21 niños y no se trataron los 10 restantes. Doce pacientes manifestaron déficit neurológico a largo plazo, mientras que 18 se mantuvieron asintomáticos. No hubo fallecimientos o complicaciones graves por la trombosis ni la anticoagulación, así como tampoco recurrencias sintomáticas en el seguimiento. Conclusiones: Las trombosis venosas cerebrales son una causa importante de ictus en la infancia. La sospecha clínica debe ser elevada ante todo paciente con clínica de hipertensión endocraneal o convulsiones en presencia de factores de riesgo conocidos.

Lymphoepithelial carcinoma in the maxillary sinus: a case report.

INTRODUCTION: Lymphoepithelial carcinoma of the maxillary sinus is a very rare malignancy and it can be difficult to make a pre-operative diagnosis. CASE PRESENTATION: A 72-year-old Caucasian woman presented to our facility with an isolated right-side epistaxis that had been present for three months, with the results of a computed tomography scan showing a soft tissue mass in the right maxillary sinus with an impacted tooth. The results of a transnasal endoscopic biopsy were compatible with a lymphoepithelial carcinoma, following which our patient underwent a radical excision of the mass. The final histology results revealed lymphoepithelial carcinoma of the maxillary sinus with negative assays for Epstein-Barr virus. Our patient was given post-operative external radiotherapy and has remained disease-free at three-year follow-up. CONCLUSIONS: This report details the diagnosis and management of a case of lymphoepithelial carcinoma of the maxillary sinus, which is a very rare malignant tumor with very little mention in the literature. Only a strong suspicion with systematic use of various patho-immunological tests helps to arrive at a definitive diagnosis by excluding other better-known tumors.

Cerebral Hypoperfusion in Posterior Reversible Encephalopathy Syndrome is Different from Transient Ischemic Attack on CT Perfusion.

BACKGROUND: PRES is a reversible neurotoxic state presenting with headache, altered mental status, visual loss, and seizures. Delayed diagnosis can be avoided if radiological patterns could distinguish PRES from cerebral ischemia. METHODS: Clinical and radiological data were collected on all hospitalized patients who had (1) discharge diagnosis of PRES and (2) acute CTP/CTA. Data were compared with 10 TIA patients with proven cytotoxic edema on MRI. RESULTS: Of the four PRES patients found, three were correlated with acute blood pressure and one with chemotherapy. At the radiological level, quantitative analyses of the CTP parameters showed that 2 out of 4 patients had bilaterally reduced CBF-values (23.2-47.1 ml/100g/min) in occipital regions, as seen in the pathological regions of TIA patients (27.3 ± 13.5 ml/100g/min). When compared with TIA patients, the pathological ROI's demonstrated decreased CBV-values (3.4-5.6 ml/100g). Vasogenic edema on MRI FLAIR imaging was seen in only one PRES patient, and cytotoxic edema on DWI-imaging was never found. CT angiography showed in one PRES patient a vasospasm-like unilateral posterior cerebral artery. CONCLUSIONS: If confirmed by other groups, CTP and CTA imaging in patients with acute visual loss and confusion may help to distinguish PRES from bi-occipital ischemia. These radiological parameters may identify PRES patients at risk for additional tissue infarction.

Metabolic gene expression changes in astrocytes in Multiple Sclerosis cerebral cortex are indicative of immune-mediated signaling.

Emerging as an important correlate of neurological dysfunction in Multiple Sclerosis (MS), extended focal and diffuse gray matter abnormalities have been found and linked to clinical manifestations such as seizures, fatigue and cognitive dysfunction. To investigate possible underlying mechanisms we analyzed the molecular alterations in histopathological normal appearing cortical gray matter (NAGM) in MS. By performing a differential gene expression analysis of NAGM of control and MS cases we identified reduced transcription of astrocyte specific genes involved in the astrocyte-neuron lactate shuttle (ANLS) and the glutamate-glutamine cycle (GGC). Additional quantitative immunohistochemical analysis demonstrating a CX43 loss in MS NAGM confirmed a crucial involvement of astrocytes and emphasizes their importance in MS pathogenesis. Concurrently, a Toll-like/IL-1β signaling expression signature was detected in MS NAGM, indicating that immune-related signaling might be responsible for the downregulation of ANLS and GGC gene expression in MS NAGM. Indeed, challenging astrocytes with immune stimuli such as IL-1β and LPS reduced their ANLS and GGC gene expression in vitro. The detected upregulation of IL1B in MS NAGM suggests inflammasome priming. For this reason, astrocyte cultures were treated with ATP and ATP/LPS as for inflammasome activation. This treatment led to a reduction of ANLS and GGC gene expression in a comparable manner. To investigate potential sources for ANLS and GGC downregulation in MS NAGM, we first performed an adjuvant-driven stimulation of the peripheral immune system in C57Bl/6 mice in vivo. This led to similar gene expression changes in spinal cord demonstrating that peripheral immune signals might be one source for astrocytic gene expression changes in the brain. IL1B upregulation in MS NAGM itself points to a possible endogenous signaling process leading to ANLS and GGC downregulation. This is supported by our findings that, among others, MS NAGM astrocytes express inflammasome components and that astrocytes are capable to release Il-1β in-vitro. Altogether, our data suggests that immune signaling of immune- and/or central nervous system origin drives alterations in astrocytic ANLS and GGC gene regulation in the MS NAGM. Such a mechanism might underlie cortical brain dysfunctions frequently encountered in MS patients.

Traitement percutané de la thrombose veineuse profonde aiguë [Catheter-based treatment for acute deep vein thrombosis].

Plus de la moitié des patients présentant une thrombose veineuse profonde des membres inférieurs développent un syndrome post-thrombotique. Le risque est particulièrement élevé en cas de thrombose de l'axe principal de drainage veineux comprenant la veine fémorale commune et les veines iliaques. Plusieurs études ont démontré que l'incidence du syndrome post-thrombotique peut être diminuée si une recanalisation des veines ilio-fémorales est obtenue dans la phase aiguë. A l'heure actuelle, des techniques de recanalisation percutanées sont proposées à des patients sélectionnés présentant une thrombose ilio-fémorale. Cet article a pour but de résumer les connaissances actuelles sur la recanalisation percutanée de la thrombose veineuse profonde aiguë. Nearly half of patients with acute lower limb deep vein thrombosis (DVT) develop a post-thrombotic syndrome (PTS). This risk is particularly high in case of proximal DVT of the common femoral and iliac vein, the major lower limbs venous outflow vessel. Several studies have demonstrated that PTS incidence can be reduced with early vein recanalisation. Currently, catheter-based recanalisation therapies can be offered to selected patients with acute ilio-femoral deep vein thrombosis. Aim of the present article is to summarize current knowledge on these catheter-based recanalisation therapies.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: effect of Anticoagulation and Its Timing: the RAF Study.

BACKGROUND AND PURPOSE: The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. METHODS: The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. RESULTS: Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). CONCLUSIONS: Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia.

Lactate has been shown to offer neuroprotection in several pathologic conditions. This beneficial effect has been attributed to its use as an alternative energy substrate. However, recent description of the expression of the HCA1 receptor for lactate in the central nervous system calls for reassessment of the mechanism by which lactate exerts its neuroprotective effects. Here, we show that HCA1 receptor expression is enhanced 24 hours after reperfusion in an middle cerebral artery occlusion stroke model, in the ischemic cortex. Interestingly, intravenous injection of L-lactate at reperfusion led to further enhancement of HCA1 receptor expression in the cortex and striatum. Using an in vitro oxygen-glucose deprivation model, we show that the HCA1 receptor agonist 3,5-dihydroxybenzoic acid reduces cell death. We also observed that D-lactate, a reputedly non-metabolizable substrate but partial HCA1 receptor agonist, also provided neuroprotection in both in vitro and in vivo ischemia models. Quite unexpectedly, we show D-lactate to be partly extracted and oxidized by the rodent brain. Finally, pyruvate offered neuroprotection in vitro whereas acetate was ineffective. Our data suggest that L- and D-lactate offer neuroprotection in ischemia most likely by acting as both an HCA1 receptor agonist for non-astrocytic (most likely neuronal) cells as well as an energy substrate.