Central Nervous System Tuberculosis in a Murine Model: Neurotropic Strains or a New Pathway of Infection?

Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of bacterial arrival to CNS, however, it remains unclear. Although the interaction of the host, the pathogen, and the environment trigger the course of the disease, in TB the characteristics of these factors seem to be more relevant in the genesis of the clinical features of each patient. We previously tested three mycobacterial clinical isolates with distinctive genotypes obtained from the cerebrospinal fluid of patients with meningeal TB and showed that these strains disseminated extensively to the brain after intratracheal inoculation and pulmonary infection in BALB/c mice. In this present study, BALB/c mice were infected through the intranasal route. One of these strains reaches the olfactory bulb at the early stage of the infection and infects the brain before the lungs, but the histological study of the nasal mucosa did not show any alteration. This observation suggests that some mycobacteria strains can arrive directly at the brain, apparently toward the olfactory nerve after infecting the nasal mucosa, and guides us to study in more detail during mycobacteria infection the nasal mucosa, the associated connective tissue, and nervous structures of the cribriform plate, which connect the nasal cavity with the olfactory bulb.

Mycobacterium tuberculosis Infection Induces BCSFB Disruption but No BBB Disruption In Vivo: Implications in the Pathophysiology of Tuberculous Meningitis.

Central nervous system (CNS) tuberculosis is the most lethal and devastating form among the diseases caused by Mycobacterium tuberculosis. The mechanisms by which M. tuberculosis bacilli enter the CNS are still unclear. However, the BBB and the BCSFB have been proposed as possible routes of access into the brain. We previously reported that certain strains of M. tuberculosis possess an enhanced ability to cause secondary CNS infection in a mouse model of progressive pulmonary tuberculosis. Here, we evaluated the morphostructural and molecular integrity of CNS barriers. For this purpose, we analyzed through transmission electron microscopy the ultrastructure of brain parenchymal microvessels and choroid plexus epithelium from animals infected with two mycobacterial strains. Additionally, we determined the expression of junctional proteins and cytokines by immunological techniques. The results showed that the presence of M. tuberculosis induced disruption of the BCSFB but no disruption of the BBB, and that the severity of such damage was related to the strain used, suggesting that variations in the ability to cause CNS disease among distinct strains of bacteria may also be linked to their capacity to cause direct or indirect disruption of these barriers. Understanding the pathophysiological mechanisms involved in CNS tuberculosis may facilitate the establishment of new biomarkers and therapeutic targets.

Reconstrucción endovascular de aneurisma intracraneal mediante dispositivo diversor de flujo Pipeline®. Reporte de 2 casos y revisión de la literatura / Endovascular reconstruction of intracranial aneurysm using a Pipeline® flow diversifier device

Resumen Introducción: Los aneurismas intracraneales son anomalías vasculares cerebrales con una prevalencia aproximada a nivel mundial del 2-3%. Son la principal causa de hemorragia subaracnoidea no traumática, el diagnóstico y tratamiento preventivo de esta entidad puede reducir considerablemente la morbimortalidad que de ella deviene. Con la aparición de nuevos dispositivos de terapia endovascular cerebral como los diversores de flujo se ha logrado ofrecer al paciente un procedimiento menos invasivo que no requiere cirugía convencional, y una importante reducción en el número de días de estancia intrahospitalaria y de recuperación, con alto grado de seguridad. El tratamiento endovascular para aneurismas intracraneales ha evolucionado sustancialmente en las últimas dos décadas, convirtiéndose en el tratamiento de elección en diversas situaciones clínicas. Reporte de caso: Caso 1: Varón de 62 años edad que ingresa a unidad hospitalaria después de sufrir un traumatismo craneoencefálico moderado con pérdida transitoria del estado de alerta y cefalea holocraneana. Se realizó una tomografía de cráneo simple y con contraste ante la sospecha de hemorragia subaracnoidea. Se evidenció la presencia de un aneurisma intracraneal en la arteria carótida interna izquierda, segmento comunicante posterior de 4 x 3 mm con cuello de 3 mm. Se realizó tratamiento mediante la colocación de dispositivo diversor de flujo Pipeline®, así como control angiográfico a los 3 meses post-tratamiento con una evolución satisfactoria. Caso 2: Mujer de 59 años de edad que acudió por presentar hemiparesia facial y brazo ipsilateral, con incremento gradual de la intensidad y duración. Se inició protocolo de estudio con resonancia magnética. Se evidenció la presencia de aneurisma intracraneal de 15 mm de diámetro en el segmento comunicante de la arteria carótida interna derecha y otro de 8 mm contralateral. Fue programada para colocación de dispositivo diversor de flujo Pipeline® con adecuada evolución. Conclusión: El uso de dispositivos diversores de flujo es una excelente alternativa para el tratamiento de aneurismas intracraneales incidentales, con importantes ventajas de costo-efectividad, reduciendo tiempos quirúrgicos, de estancia hospitalaria y de recuperación. Además de tener un porcentaje de curación superior al 95% a 5 años.

Abstract Introduction: Intracranial aneurysms are cerebral vascular anomalies with an approximate global prevalence of 2 to 3% and are the main cause of non-traumatic subarachnoid hemorrhage. Diagnosis and preventive treatment of this entity can considerably reduce morbidity and mortality. With the advent of new devices for cerebral endovascular therapy such as flow diverters, the patient now has the option of choosing a less invasive procedure, which does not require conventional surgery. This represents a significant reduction in the number of days of in hospital stay and recovery. The procedure has showed a high degree of security. The endovascular treatment for intracranial aneurysms has evolved substantially in the last two decades, and has become the treatment of choice. Case report: Case 1: A 62-year-old male was admitted in the hospital after a moderate cranioencephalic trauma with transient loss of conscious and a holocranial headache. A cerebral angiography was performed to rule out subarachnoid hemorrhage. The angiography showed an intracranial aneurysm. It was localized in left internal carotid-posterior communicating artery. The measures were of 4mm X 3mm with a 3mm neck. The treatment was performed with a pipeline flow-diverting device, as well as an angiographic control 3 months after the treatment with a satisfactory evolution. Case 2: A 59-year-old female patient with facial hemiparesis and ipsilateral arm, that showed a gradual increase in intensity and duration. A magnetic resonance study protocol was initiated and an intracranial aneurysm was observed in the communicating segment of the right internal carotid artery. The diameter of the aneurysmal sac was of 15 mm and also, a contralateral of 8 mm. Placement of a flow-diverting device was programmed. Conclusion: The use of flow-diverting devices is an excellent alternative for the treatment of incidental intracranial aneurysms, with important cost-effectiveness advantages, surgical time, hospital stay and recovery reduction. In addition to having a recovery percentage of 95% in 5 years.