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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]

Introduction: The plasticity of the neural circuits after injuries has been extensively investigated over the last decades. Transcallosal microsurgery for lesions affecting the third ventricle offers an interesting opportunity to investigate the whole-brain white matter reorganization occurring after a selective resection of the genu of the corpus callosum (CC). Method: Diffusion MRI (dMRI) data and neuropsychological testing were collected pre- and postoperatively in six patients with colloid cysts, surgically treated with a transcallosal-transgenual approach. Longitudinal connectometry analysis on dMRI data and graph analysis on structural connectivity matrix were implemented to analyze how white matter pathways and structural network topology reorganize after surgery. Results: Although a significant worsening in cognitive functions (e.g., executive and memory functioning) at early postoperative, a recovery to the preoperative status was observed at 6 months. Connectometry analysis, beyond the decrease of quantitative anisotropy (QA) near the resection cavity, showed an increase of QA in the body and forceps major CC subregions, as well as in the left intra-hemispheric corticocortical associative fibers. Accordingly, a reorganization of structural network topology was observed between centrality increasing in the left hemisphere nodes together with a rise in connectivity strength among mid and posterior CC subregions and cortical nodes. Conclusion: A structural reorganization of intra- and inter-hemispheric connective fibers and structural network topology were observed following the resection of the genu of the CC. Beyond the postoperative transient cognitive impairment, it could be argued anterior CC resection does not preclude neural plasticity and may subserve the long-term postoperative cognitive recovery. [ABSTRACT FROM AUTHOR]

We previously found that the endogenous anticonvulsant adenosine, acting through [A.sub.2A] and [A.sub.3] adenosine receptors (ARs), alters the stability of currents ([I.sub.GABA]) generated by GABAA receptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether ARs alter the stability (desensitization) of [I.sub.GABA] expressed in focal cortical dysplasia (FCD) and in periglioma epileptic tissues. The experiments were performed with tissues from 23 patients, using voltage-clamp recordings in Xenopus oocytes microinjected with membranes isolated from human MTLE and FCD tissues or using patch-clamp recordings of pyramidal neurons in epileptic tissue slices. On repetitive activation, the epileptic GABAA receptors revealed instability, manifested by a large [I.sub.GABA] rundown, which in most of the oocytes ([approximately equal to] 70%) was obviously impaired by the new [A.sub.2A] antagonists ANR82, ANR94, and ANR152. In most MTLE tissue-microtransplanted oocytes, a new [A.sub.3] receptor antagonist (ANR235) significantly improved [I.sub.GABA] stability. Moreover, patch-clamped pyramidal neurons from human neocortical slices of periglioma epileptic tissues exhibited altered [I.sub.GABA] rundown on ANR94 treatment. Our findings indicate that antagonizing [A.sub.2A] and [A.sub.3] receptors increases the [I.sub.GABA] stability in different epileptic tissues and suggest that adenosine derivatives may offer therapeutic opportunities in various forms of human epilepsy. epilepsy | focal cortical dysplasia

Introduction: Pre-surgical mapping is clinically essential in the surgical management of brain tumors to preserve functions. A common technique to localize eloquent areas is functional magnetic resonance imaging (fMRI). In tumors involving the peri-rolandic regions, the finger tapping task (FTT) is typically administered to delineate the functional activation of hand-knob area. However, its selectivity may be limited. Thus, here, a novel cue-induced fMRI task was tested, the visual-triggered finger movement task (VFMT), aimed at eliciting a more accurate functional cortical mapping of the hand region as compared with FTT. Method: Twenty patients with glioma in the peri-rolandic regions underwent pre-operative mapping performing both FTT and VFMT. The fMRI data were analyzed for surgical procedures. When the craniotomy allowed to expose the motor cortex, the correspondence with intraoperative direct electrical stimulation (DES) was evaluated through sensitivity and specificity (mean sites = 11) calculated as percentage of true-positive and true-negative rates, respectively. Results: Both at group level and at single-subject level, differences among the tasks emerged in the functional representation of the hand-knob. Compared with FTT, VFMT showed a well-localized activation within the hand motor area and a less widespread activation in associative regions. Intraoperative DES confirmed the greater specificity (97%) and sensitivity (100%) of the VFMT in determining motor eloquent areas. Conclusion: The study provides a novel, external-triggered fMRI task for pre-surgical motor mapping. Compared with the traditional FTT, the new VFMT may have potential implications in clinical fMRI and surgical management due to its focal identification of the hand-knob region and good correspondence to intraoperative DES. [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]

Abstract Purpose The purpose of this study was to report long-term seizure outcome in patients who underwent frontal lobe epilepsy (FLE) surgery. Method This retrospective study included 44 consecutive subjects who underwent resective surgery for intractable FLE at IRCCS NEUROMED (period 2001–2014), followed up for at least 2 years (mean: 8.7 years). All patients underwent noninvasive presurgical evaluation and/or invasive electroencephalography (EEG) monitoring when nonconcordant data were obtained or epileptogenic zone was hypothesized to be close to the eloquent cortex. Electroclinical, neuroimaging, surgical data, and histology were compared to seizure outcome. Results Mean epilepsy duration was 19 years; mean age at surgery was 31.6 years. Preoperative magnetic resonance imaging (MRI) showed a frontal lesion in 86.4 % of cases. Scalp video-electroencephalography (VEEG) monitoring detected a focal ictal onset in 90% of cases. Twenty-seven patients (61.4%) underwent invasive recordings. Resections involved dorsolateral (47.7%), medial (9%), orbital (13.6%), and rolandic (13.6%) region. Lobectomy within functional boundaries was performed in the remaining 7 cases (16%). Transient and permanent neurological deficits were observed in 2 and 3 cases, respectively. Histology revealed focal cortical dysplasia (45.5%), World Health Organization (WHO) I–II grade tumors (15.9%), gliosis (22.7%), vascular malformations (4.5%), Rasmussen encephalitis (6.8%), and normal tissue (4.5%). At last observation 68.1% of patients were in Engel's class I, 11.4% in class II, 9% in class III, and 11.4% in class IV. A favorable outcome was associated with focal ictal scalp EEG onset (p = 0.0357). Conclusion Surgery is a safe treatment option in drug-resistant FLE with a satisfying long-term outcome. These data highlight the importance of an appropriate selection of potential surgical candidates. Highlights • Surgery is a safe option in drug-resistant FLE with a satisfying long-term outcome. • The presence of focal lesions predicts favorable outcome. • Focal ictal scalp EEG onset is associated with a favorable long-term outcome. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor alpha (PPARa) has been involved in the regulation of somatotroph tumour cells and may be targeted by different drugs, some of them are in current clinical use. The aim of this study was to investigate the expression of PPARa in additional phenotypes of pituitary adenomas (PA), the relationship between PPARa and its potential molecular partner aryl hydrocarbon receptor interacting protein (AIP) in these tumours, and the effects of PPARa agonists on lactotroph cells. Seventy-five human PA - 57 non-functioning (NFPA) and 18 prolactinomas (PRL-PA) - were characterised for PPARa and AIP expression by real time RT-PCR and/or immunohistochemistry (IHC), and the effects of fenofibrate and WY 14 643 on MMQ cells were studied in vitro. PPARa was expressed in a majority of PA. PPARa immunostaining was observed in 93.7% PRL-PA vs. 60.6% NFPA (p = 0.016), the opposite being found for AIP (83.3% in NFPA vs. 43.7% in PRL-PA, p = 0.003). PPARa expression was unrelated to gonadotroph differentiation in NFPA, but positively correlated with tumour volume in PRL-PA. Both drugs significantly reduced MMQ cell growth at high concentrations (100-200 µM). At the same time, despite modest stimulating effects on PRL secretion were observed, these were overcome by the reduction in cell number. In conclusion, PPARa is commonly expressed by PRL-PA and NFPA, regardless of AIP, and may represent a new target of PPARa agonists. [ABSTRACT FROM AUTHOR]

We have previously shown that in seven drug-resistant epilepsy patients, both reaching-grasping of objects and the mere observation of those actions did desynchronize subdural electrocorticographic (ECoG) alpha (8-13 Hz) and beta (14-30) rhythms as a sign of cortical activation in primary somatosensory-motor, lateral premotor and ventral prefrontal areas (Babiloni et al., 2016a). Furthermore, that desynchronization was greater during action execution than during its observation. In the present exploratory study, we reanalyzed those ECoG data to evaluate the proof-of-concept that lagged linear connectivity (LLC) between primary somatosensory-motor, lateral premotor and ventral prefrontal areas would be enhanced during the action execution compared to the mere observation due to a greater flow of visual and somatomotor information. Results showed that the delta-theta (<8 Hz) LLC between lateral premotor and ventral prefrontal areas was higher during action execution than during action observation. Furthermore, the phase of these delta-theta rhythms entrained the local event-related connectivity of alpha and beta rhythms. It was speculated the existence of a multi-oscillatory functional network between high-order frontal motor areas which should be more involved during the actual reaching-grasping of objects compared to its mere observation. Future studies in a larger population should cross-validate these preliminary results. [ABSTRACT FROM AUTHOR]

We previously found that the endogenous anticonvulsant adenosine, acting through A2A and A3 adenosine receptors (ARs), alters the stability of currents (IGABA) generated by GABAA receptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether AR5 alter the stability (desensitization) of IGABA expressed in focal cortical dysplasia (FCD) and in penglioma epileptic tissues. The experiments were performed with tissues from 23 patients, using voltage-clamp recordings in Xenopus oocytes microinjected with membranes isolated from human MTLE and FCD tissues or using patch-clamp recordings of pyramidal neurons in epileptic tissue slices. On repetitive activation, the epileptic GABAA receptors revealed instability, manifested by a large IGABA rundown, which in most of the oocytes (≈70%) was obviously impaired by the new A2A antagonists ANR82, ANR94, and ANR152. In most MILE tissue-microtransplanted oocytes, a new A3 receptor antagonist (ANR235) significantly improved IGABA stability. Moreover, patch-clamped pyramidal neurons from human neocortical slices of periglioma epileptic tissues exhibited altered IGABA rundown on ANR94 treatment. Our findings indicate that antagonizing A2A and A3 receptors increases the IGABA stability in different epileptic tissues and suggest that adenosine derivatives may offer therapeutic opportunities in various forms of human epilepsy. [ABSTRACT FROM AUTHOR]

Background: Ictal asystole (IA) is a rare event observed in people with epilepsy (PwE). Clinical and IA video-electroencephalographic findings may be helpful in screening for high-risk subjects. Methods: From all PwE undergoing video-EEG for presurgical evaluation between 2000 and 2019, we retrospectively selected those with at least one IA (R–R interval of ≥3 s during a seizure). Results: IA was detected in eight out of 1088 (0.73%) subjects (mean age: 30 years; mean epilepsy duration: 9.6 years). Four out of them had a history of atonic falls. No patients had cardiac risk factors or cardiovascular diseases. Seizure onset was temporal (n = 5), temporo-parietal (n = 1) or frontal (n = 2), left-sided and right-sided in five and two patients, respectively. In one case a bilateral temporal independent seizure onset was recorded. IA was recorded in 11 out of 18 seizures. Mean IA duration was 13 s while mean IA latency from seizure onset was 26.7 s. Symptoms related to IA were observed in all seizures. Conclusion: IA is a rare and self-limiting event often observed during video-EG in patients with a history of atonic loss of consciousness and/or tardive falls in the course of a typical seizure. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

• Postoperative SRS is usually recommended for resected brain metastases. • 3 x 9 Gy demonstrates activity in both intact and resected large NSCLC metastases. • Local control is comparable between resected and intact large brain metastases. • A worse safety profile can be expected after surgery and postoperative SRS (3 x 9 Gy). Purpose: to investigate clinical outcomes in patients with large brain metastases from non-small-cell lung cancer (NSCLC) who received surgical resection and postoperative stereotactic radiosurgery or SRS alone. Patients and Methods: Two hundred and twenty-two patients with 241 large brain metastases (2–4 cm in size) who received surgery and multi-fraction SRS (mfSRS) to the resection cavity or mfSRS alone were analyzed. For all lesions the delivered dose was 3 x 9 Gy over three consecutive days. Primary endpoint of the study was local control (LC). Secondary endpoints included early improvement of neurological deficits, changes in performance status, treatment-related toxicity, radiation-induced brain necrosis (RN), distant brain failure (DBF), and overall survival (OS). Kaplan-Meier analysis and cumulative incidence function were used for comparing the probability of failure. Results: At a median follow-up of 13 months, median OS times and 1-year survival rates were comparable: 13.5 months and 59% for patients receiving surgery and postoperative mfSRS to the resection cavity and 15.2 months and 68% for those treated with mfSRS alone (p = 0.2). Median DBF did not differ significantly between groups (surgery and mfSRS,12 months; mfSRS,14 months). Eighteen patients receiving surgery and mfSRS and 17 patients treated with mfSRS alone recurred locally (p = 0.2); respective 6-month and 12-month LC rates were 87% and 83% and 96% and 91% (p = 0.15). The 1-year cumulative incidence rates of RN were 15% and 7% after postoperative mfSRS and mfSRS alone (p = 0.03), respectively. Conclusions: In conclusion, mfSRS is an effective treatment for patients with large brain metastases from NSCLC resulting in equivalent LC and lower RN and risk of leptomeningeal spread compared to surgery and mf-SRS to the resection cavity. Surgery is an effective treatment option for patients with large symptomatic brain metastases who require rapid relief of neurological symptoms caused by tumor mass effect. [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.

Despite the relevance of inhibitory control in shaping our behavior its neural substrates are still hotly debated. In this regard, it has been suggested that inhibitory control relies upon a right-lateralized network which involves the right subthalamic nucleus (STN). To assess the role of STN, we took advantage of a relatively rare model, i.e., advanced Parkinson's patients who received unilateral deep-brain stimulation (DBS) of the STN either of the left ( n = 10) or of the right ( n = 10) hemisphere. We gave them a stop-signal reaching task, and we compared patients' performance in two experimental conditions, DBS-ON and DBS-OFF. In addition, we also tested 22 age-matched healthy participants. As expected, we found that inhibitory control is impaired in Parkinson's patients with respect to healthy participants. However, neither reactive nor proactive inhibition is improved when either the right or the left DBS is active. We interpreted these findings in light of the fact that previous studies, exploiting exactly the same task, have shown that only bilateral STN DBS restores a near-normal inhibitory control. Thus, although null results have to be interpreted with caution, our current findings confirm that the right STN does not play a key role in suppressing pending actions. However, on the ground of previous studies, it is very likely that this subcortical structure is part of the brain network subserving inhibition but to implement this executive function both subthalamic nuclei must be simultaneously active. Our findings are of significance to other researchers studying the effects of STN DBS on key executive functions, such as impulsivity and inhibition and they are also of clinical relevance for determining the therapeutic benefits of STN DBS as they suggest that, at least as far as inhibitory control is concerned, it is better to implant DBS bilaterally than unilaterally.

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.

Objective: More and more commonly, craniotomies are being performed with minimal hair shaving to improve cosmesis and facilitate return to a normal life. In such patients, traditional sutures or metal staples are used for scalp closure. This practice requires suture removal, often perceived as a cause of discomfort by the patient. We investigate the safety and efficacy of intradermal sutures in a large, consecutive series of patients undergoing elective craniotomy., Methods: Wound healing complications were investigated in a consecutive series of 208 patients who underwent elective craniotomy during a 2-year period. In all patients, minimal shaving, performed by shaving a small strip of hair along the planned wound, was used. Scalp closure was achieved with only absorbable intradermal running sutures. All wounds were covered with sterile adhesive strips, which were kept in place for 24 hours postoperatively. Patients were followed for a mean follow-up period of 10.6 months (range, 1-23 mo)., Results: All patients except two had satisfactory wound healing. One patient (0.48%) developed cerebrospinal fluid leakage, which responded to bed rest and lumbar drainage. Another patient (0.48%) had a superficial skin infection, which was successfully treated with topical wound care and oral antibiotics., Conclusion: The closure method described is safe and effective. The absence of visible sutures in the postoperative course reinforces the cosmetic advantage of no shaving and decreases discomfort associated with the removal of sutures or staples.

Spinal extradural arteriovenous fistulas (AVFs) are rare lesions that may be associated with neurofibromatosis Type 1 (NF1). In these patients, the shunt typically occurs between the V(2) segment of the vertebral artery and the epidural venous plexus. Previously, reported cases have been treated either by using endovascular embolization or, sporadically, by open surgery. In surgical reports, proximal deafferentation or manipulation of the venous portion of the shunt--including suture, resection, or open embolization of the epidural ectasia--was attempted with variable results. The authors report on a case of a young patient with NF1 who underwent emergency surgical disconnection of a cervical extradural AVF after previously unsuccessful endovascular and surgical therapy. The lesion drained into a giant intrathecal varix, causing severe myelopathy. After surgery, the patient recovered almost completely. This experience clarified the surgical anatomy of these malformations and showed that, when surgery is necessary, the optimal treatment providing complete and permanent cure of this condition is direct closure of the epidural shunt pedicle.

The management of cavernous malformations of the brain is markedly influenced by the location of the lesions themselves. In the last decade, resection of cavernomas arising in the dominant insular lobe has been deemed safe only with the guidance of neuronavigation. Most navigation equipment, however, shares some minor drawbacks, including costs, longer operating time, and a variable loss of accuracy due to intraoperative brain shift. In this paper the authors present the case of a left dominant insular cavernoma that was successfully removed using a novel form of navigation that they call magnetic resonance imaging-based corticotopography. This technique, which is unaffected by the brain shift phenomenon, provided a simple and inexpensive alternative to standard neuronavigation. Selected cases of subcortical brain lesions could be conveniently approached using the same technique.

Object: Supratentorial cavernous angiomas may be associated with drug-resistant focal epilepsy. Surgical removal of the malformation may result in seizure control in a number of patients, although in most studies a long history and high frequency of attacks have been recognized as indicators of unfavorable seizure outcome. In the literature, there are no clear indications regarding the optimal diagnostic presurgical workup and the surgical strategy for this particular subgroup of patients with symptomatic epilepsy. In this paper the authors focus on the preoperative workup and the surgical management of the disease in eight consecutive patients undergoing surgery for drug-resistant temporal lobe epilepsy (TLE) due to cavernous malformations (CMs), and the relevant literature on this issue is also reviewed., Methods: Preoperatively, all patients were assessed using a noninvasive protocol aimed at localizing the epileptogenic zone on the basis of anatomical, electrical, and clinical criteria. The presurgical assessment yielded an indication for lesionectomy in two cases, lesionectomy plus anteromesial temporal lobectomy in four cases, and lesionectomy plus extended temporal lobectomy in two cases. At follow-up examinations, seizure, neuropsychological, and psychiatric outcomes were all evaluated. Seven patients were categorized in Engel Class IA (seizure free), and one was categorized in Engel Class IB (occasional auras only). No adverse effects on neuropsychological or psychosocial functioning were observed., Conclusions: Epilepsy surgery can be performed with excellent results in patients with intractable TLE caused by CMs. Noninvasive presurgical evaluation of these patients may enable a tailored approach, providing complete seizure relief in most cases.