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BackgroundIntracellular Ca2+ modulates several microglial activities, such as proliferation, migration, phagocytosis, and inflammatory mediator secretion. Extracellular ATP, the levels of which significantly change during epileptic seizures, activates specific receptors leading to an increase of intracellular free Ca2+ concentration ([Ca2+]i). Here, we aimed to functionally characterize human microglia obtained from cortices of subjects with temporal lobe epilepsy, focusing on the Ca2+-mediated response triggered by purinergic signaling.MethodsFura-2 based fluorescence microscopy was used to measure [Ca2+]i in primary cultures of human microglial cells obtained from surgical specimens. The perforated patch-clamp technique, which preserves the cytoplasmic milieu, was used to measure ATP-evoked Ca2+-dependent whole-cell currents.ResultsIn human microglia extracellular ATP evoked [Ca2+]i increases depend on Ca2+ entry from the extracellular space and on Ca2+ mobilization from intracellular compartments. Extracellular ATP also induced a transient fivefold potentiation of the total transmembrane current, which was completely abolished when [Ca2+]i increases were prevented by removing external Ca2+ and using an intracellular Ca2+ chelator. TRAM-34, a selective KCa3.1 blocker, significantly reduced the ATP-induced current potentiation but did not abolish it. The removal of external Cl- in the presence of TRAM-34 further lowered the ATP-evoked effect. A direct comparison between the ATP-evoked mean current potentiation and mean Ca2+ transient amplitude revealed a linear correlation. Treatment of microglial cells with LPS for 48 h did not prevent the ATP-induced Ca2+ mobilization but completely abolished the ATP-mediated current potentiation. The absence of the Ca2+-evoked K+ current led to a less sustained ATP-evoked Ca2+ entry, as shown by the faster Ca2+ transient kinetics observed in LPS-treated microglia.ConclusionsOur study confirms a functional role for KCa3.1 channels in human microglia, linking ATP-evoked Ca2+ transients to changes in membrane conductance, with an inflammation-dependent mechanism, and suggests that during brain inflammation the KCa3.1-mediated microglial response to purinergic signaling may be reduced.

Cerebrospinal fluid (CSF) leak through petrosal air cells is a known complication after drilling the posterior wall of the internal acoustic canal (IAC) for resection of vestibular schwannoma (VS). Whereas mild pneumocephalus is common after retrosigmoid craniotomy, tension pneumocephalus has been rarely documented. To testify a case of fatal tension pneumocephalus after VS resection in a patient with ventriculo-peritoneal (VP) shunt and to propose possible recommendations to limit the risk of this dramatic complication. A case of fatal tension pneumocephalus after VS resection in presence of hidden CSF fistula is illustrated with pre- and post-operative images. In the uneventful situation of concomitant post-operative CSF fistula in presence of VP shunt, tension pneumocephalus may occur. The negative pressure created by the shunt system and the presence of osteo-dural defect allow the air to enter and, at the same time, prevent the outflow. After VS resection, tension pneumocephalus can occur as a consequence of CSF fistula from petrosal air cells in the presence of functioning VP shunt. Precautions as pre-operative increase to 'virtual-off' the pressure of the valve, subsequences CT scans after surgery and sealing of the petrous air cells are recommended to avoid such as fatal complication. [ABSTRACT FROM AUTHOR]

Background: Intracellular Ca2+ modulates several microglial activities, such as proliferation, migration, phagocytosis, and inflammatory mediator secretion. Extracellular ATP, the levels of which significantly change during epileptic seizures, activates specific receptors leading to an increase of intracellular free Ca2+ concentration ([Ca2+]i). Here, we aimed to functionally characterize human microglia obtained from cortices of subjects with temporal lobe epilepsy, focusing on the Ca2+-mediated response triggered by purinergic signaling.Methods: Fura-2 based fluorescence microscopy was used to measure [Ca2+]i in primary cultures of human microglial cells obtained from surgical specimens. The perforated patch-clamp technique, which preserves the cytoplasmic milieu, was used to measure ATP-evoked Ca2+-dependent whole-cell currents.Results: In human microglia extracellular ATP evoked [Ca2+]i increases depend on Ca2+ entry from the extracellular space and on Ca2+ mobilization from intracellular compartments. Extracellular ATP also induced a transient fivefold potentiation of the total transmembrane current, which was completely abolished when [Ca2+]i increases were prevented by removing external Ca2+ and using an intracellular Ca2+ chelator. TRAM-34, a selective KCa3.1 blocker, significantly reduced the ATP-induced current potentiation but did not abolish it. The removal of external Cl- in the presence of TRAM-34 further lowered the ATP-evoked effect. A direct comparison between the ATP-evoked mean current potentiation and mean Ca2+ transient amplitude revealed a linear correlation. Treatment of microglial cells with LPS for 48 h did not prevent the ATP-induced Ca2+ mobilization but completely abolished the ATP-mediated current potentiation. The absence of the Ca2+-evoked K+ current led to a less sustained ATP-evoked Ca2+ entry, as shown by the faster Ca2+ transient kinetics observed in LPS-treated microglia.Conclusions: Our study confirms a functional role for KCa3.1 channels in human microglia, linking ATP-evoked Ca2+ transients to changes in membrane conductance, with an inflammation-dependent mechanism, and suggests that during brain inflammation the KCa3.1-mediated microglial response to purinergic signaling may be reduced. [ABSTRACT FROM AUTHOR]

Background: Intracellular Ca 2+ modulates several microglial activities, such as proliferation, migration, phagocytosis, and inflammatory mediator secretion. Extracellular ATP, the levels of which significantly change during epileptic seizures, activates specific receptors leading to an increase of intracellular free Ca 2+ concentration ([Ca 2+ ] i ). Here, we aimed to functionally characterize human microglia obtained from cortices of subjects with temporal lobe epilepsy, focusing on the Ca 2+ -mediated response triggered by purinergic signaling., Methods: Fura-2 based fluorescence microscopy was used to measure [Ca 2+ ] i in primary cultures of human microglial cells obtained from surgical specimens. The perforated patch-clamp technique, which preserves the cytoplasmic milieu, was used to measure ATP-evoked Ca 2+ -dependent whole-cell currents., Results: In human microglia extracellular ATP evoked [Ca 2+ ] i increases depend on Ca 2+ entry from the extracellular space and on Ca 2+ mobilization from intracellular compartments. Extracellular ATP also induced a transient fivefold potentiation of the total transmembrane current, which was completely abolished when [Ca 2+ ] i increases were prevented by removing external Ca 2+ and using an intracellular Ca 2+ chelator. TRAM-34, a selective K Ca 3.1 blocker, significantly reduced the ATP-induced current potentiation but did not abolish it. The removal of external Cl - in the presence of TRAM-34 further lowered the ATP-evoked effect. A direct comparison between the ATP-evoked mean current potentiation and mean Ca 2+ transient amplitude revealed a linear correlation. Treatment of microglial cells with LPS for 48 h did not prevent the ATP-induced Ca 2+ mobilization but completely abolished the ATP-mediated current potentiation. The absence of the Ca 2+ -evoked K + current led to a less sustained ATP-evoked Ca 2+ entry, as shown by the faster Ca 2+ transient kinetics observed in LPS-treated microglia., Conclusions: Our study confirms a functional role for K Ca 3.1 channels in human microglia, linking ATP-evoked Ca 2+ transients to changes in membrane conductance, with an inflammation-dependent mechanism, and suggests that during brain inflammation the K Ca 3.1-mediated microglial response to purinergic signaling may be reduced.

Background: Presacral schwannomas are rare benign tumors that may reach large size before becoming symptomatic. Total surgical removal has been considered the best treatment option. Tumors arising from the presacral area are commonly managed through anterior approaches, whereas posterior approaches are used for pure intrasacral tumors or large lesions with both intrasacral and presacral extension, alone or in combination with anterior approaches., Methods: We describe a quick and minimally invasive navigation-guided posterolateral approach to a right presacral L5 schwannoma. The lesion was microsurgically removed through high-speed drilling of the upper portion of the right sacral ala, under intraoperative neurophysiologic monitoring., Results: The postoperative course was unremarkable, and the patient experienced improvement in his sensory disturbance. Postoperative magnetic resonance imaging and computed tomography scan showed the complete excision of the lesion and the removal of the upper sacral ala with preservation of the right L5-S1 articular complex. The histologic examination confirmed a schwannoma (World Health Organization grade I)., Conclusions: The posterolateral transsacral ala approach may represent a minimally invasive option in the surgical management of presacral well-circumscribed benign tumors. Spinal navigation could be properly used to facilitate lesion exposure and to minimize the bone removal. The intraoperative neurophysiologic monitoring is an essential tool for the preservation of the lumbosacral nerve roots., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Craniopharyngiomas are disembryogenetic, benign, tumors that origin from squamous epithelial remnants of Rathke's pouch, developing from any segment of its course, virtually from rhino-pharynx to the hypothalamus. Historically, different microscopic transcranial routes, have been advocated as possible surgical options for the treatment of craniopharyngiomas. The endonasal technique offers a direct approach that permits access to the suprasellar, retrosellar and retroclival space, obviating brain retraction; it provides the advantage of appraoching cranioopharyngiomas without optic nerve manipulation and/or retraction. We herein present the surgical nuances of the endoscopic endonasal approach for the treatment of craniopharyngiomas, highlighting hints, advantages and drawbacks, also in regards of the anatomy dealt with. The endoscopic endonasal technique has been emerging as a viable approach/alternative for the treatment of this disease as the endoscope itself increased its safety and effectiveness. It allows the removal of both infra and supradiaphragmatic lesions - eventually involving the third ventricle chamber but not extending laterally off the ICA out of the visibility and maneuverability of the instruments - avoiding brain and optic nerve manipulation and retraction, with good visualization of the pituitary gland and stalk and the main neurovascular structures.

Introduction: Deep brain stimulation (DBS) is currently considered a promising neuromodulation therapy for refractory epilepsy not suitable for resective surgery. Several anatomical targets and different stimulation approaches have been proposed in order to obtain satisfactory seizures reduction. As expected, according with different patterns of neural pathways involvement, the efficacy of each anatomical target stimulation in reducing seizure frequency varies among the different epileptic syndromes., Evidence Acquisition: We reviewed the current literature on this topic to provide an overview of the clinical efficacy of the main stimulation targets (anterior nucleus of the thalamus [ANT], hippocampus formation [HF] and centromedian nucleus of the thalamus [CMT]) related to the different epileptic syndromes. We also summarized the available data concerning side effects, neuropsychological outcome, quality of life and future perspective of DBS in intractable epilepsy., Evidence Synthesis: Encouraging results were reported for each target stimulation. However, only in ANT and responsive neurostimulation (RNS) the efficacy and safety were tested on large series of patients and achieving class I evidence level., Conslusions: We concluded that responsive stimulation could be more appropriate in focal epilepsy, while ANT stimulation could be properly performed also in multifocal seizures with predominant limbic involvement. Despite the small samples size, HF stimulation reduces seizure frequency in (bi) temporal lobe epilepsy, as well as CMT stimulation is able to reduce, seizure frequency, in generalized epilepsy.