Time course of outcome in poor grade subarachnoid hemorrhage patients: a longitudinal retrospective study.

BACKGROUND: Neurological outcome and mortality of patients suffering from poor grade subarachnoid hemorrhage (SAH) may have changed over time. Several factors, including patients' characteristics, the presence of hydrocephalus and intraparenchymal hematoma, might also contribute to this effect. The aim of this study was to assess the temporal changes in mortality and neurologic outcome in SAH patients and identify their predictors. METHODS: We performed a single center retrospective cohort study from 2004 to 2018. All non-traumatic SAH patients with poor grade on admission (WFNS score of 4 or 5) who remained at least 24 h in the hospital were included. Time course was analyzed into four groups according to the years of admission (2004-2007; 2008-2011; 2012-2015 and 2016-2018). RESULTS: A total of 353 patients were included in this study: 202 patients died (57 %) and 260 (74 %) had unfavorable neurological outcome (UO) at 3 months. Mortality tended to decrease in in 2008-2011 and 2016-2018 periods (HR 0.55 [0.34-0.89] and HR 0.33 [0.20-0.53], respectively, when compared to 2004-2007). The proportion of patients with UO remained high and did not vary significantly over time. Patients with WFNS 5 had higher mortality (68 % vs. 34 %, p = 0.001) and more frequent UO (83 % vs. 54 %, p = 0.001) than those with WFNS 4. In the multivariable analysis, WFNS 5 was independently associated with mortality (HR 2.12 [1.43-3.14]) and UO (OR 3.23 [1.67-6.25]). The presence of hydrocephalus was associated with a lower risk of mortality (HR 0.60 [0.43-0.84]). CONCLUSIONS: Both hospital mortality and UO remained high in poor grade SAH patients. Patients with WFNS 5 on admission had worse prognosis than others; this should be taken into consideration for future clinical studies.

Freehand stereotactic ventricular catheter insertion for ventriculoperitoneal shunts based on individualized radio-anatomical landmarks.

INTRODUCTION: The accurate placement of the ventricular catheter (VC) is critical in reducing the incidence of proximal failure of ventriculoperitoneal shunts (VPSs). The standard freehand technique is based on validated external anatomical landmarks but remains associated with a relatively high rate of VC malposition. Already proposed alternative methods have all their specific limitations. Herein, we evaluate the accuracy of our adapted freehand technique based on an individualized radio-anatomical approach. Reproducing the preoperative imaging on the patient's head using common anatomical landmarks allows to define stereotactic VC coordinates to be followed at surgery. MATERIAL AND METHODS: Fifty-five consecutive patients treated with 56 VPS between 11/2005 and 02/2020 fulfilled the inclusion criteria of this retrospective study. Burr hole coordinates, VC trajectory, and length were determined in all cases on preoperative computed tomography (CT) scan and were accurately reported on patients' head. The primary endpoint was to evaluate VC placement accuracy. The secondary endpoint was to evaluate the rate and nature of postoperative VC-related complications. RESULTS: Our new technique was applicable in all patients and no VC-related complications were observed. Postoperative imaging showed VC optimally placed in 85.7% and sub-optimally placed in 14.3% of cases. In all procedures, all the holes on the VC tip were found in the ventricular system. CONCLUSIONS: This simple individualized technique improves the freehand VC placement in VPS surgery, making its accuracy comparable to that of more sophisticated and expensive techniques. Further randomized controlled studies are required to compare our results with those of the other available techniques.

Safety profile of an intracranial multimodal monitoring bolt system for neurocritical care: a single-center experience.

BACKGROUND: Intracranial multimodality monitoring (iMMM) is increasingly used in acute brain-injured patients; however, safety and reliability remain major concerns to its routine implementation. METHODS: We performed a retrospective study including all patients undergoing iMMM at a single European center between July 2016 and January 2020. Brain tissue oxygenation probe (PbtO2), alone or in combination with a microdialysis catheter and/or an 8-contact depth EEG electrode, was inserted using a triple-lumen bolt system and targeting normal-appearing at-risk brain area on the injured side, whenever possible. Surgical complications, adverse events, and technical malfunctions, directly associated with iMMM, were collected. A blinded imaging review was performed by an independent radiologist. RESULTS: One hundred thirteen patients with 123 iMMM insertions were included for a median monitoring time of 9 [3-14] days. Of those, 93 (76%) patients had only PbtO2 probe insertion and 30 (24%) had also microdialysis and/or iEEG monitoring. SAH was the most frequent indication for iMMM (n = 60, 53%). At least one complication was observed in 67/123 (54%) iMMM placement, corresponding to 58/113 (51%) patients. Misplacement was observed in 16/123 (13%), resulting in a total of 6/16 (38%) malfunctioning PbtO2 catheters. Intracranial hemorrhage was observed in 14 iMMM placements (11%), of which one required surgical drainage. Five placements were complicated by pneumocephalus and 4 with bone fragments; none of these requires additional surgery. No CNS infection related to iMMM was observed. Seven (6%) probes were accidentally dislodged and 2 probes (2%) were accidentally broken. Ten PbtO2 probes (8%) presented a technical malfunction after a median of 9 [ranges: 2-24] days after initiation of monitoring and 4 of them were replaced. CONCLUSIONS: In this study, a high occurrence of complications related to iMMM was observed, although most of them did not require specific interventions and did not result in malfunctioning monitoring.

Sepsis is associated with altered cerebral microcirculation and tissue hypoxia in experimental peritonitis.

OBJECTIVE: Alterations in cerebral microvascular blood flow may develop during sepsis, but the consequences of these abnormalities on tissue oxygenation and metabolism are not well defined. We studied the evolution of microvascular blood flow, brain oxygen tension (PbO2), and metabolism in a clinically relevant animal model of septic shock. DESIGN: Prospective randomized animal study. SETTING: University hospital research laboratory. SUBJECTS: Fifteen invasively monitored and mechanically ventilated female sheep. INTERVENTIONS: The sheep were randomized to fecal peritonitis (n = 10) or a sham procedure (n = 5), and craniectomies were performed to enable evaluation of cerebral microvascular blood flow, PbO2, and metabolism. The microvascular network of the left frontal cortex was evaluated (at baseline, 6, 12, and 18 hr) using sidestream dark-field videomicroscopy. Using an off-line semiquantitative method, functional capillary density and the proportion of small perfused vessels were calculated. PbO2 was measured hourly by a parenchymal Clark electrode, and cerebral metabolism was assessed by the lactate/pyruvate ratio using brain microdialysis; both these systems were placed in the right frontal cortex. MEASUREMENT AND MAIN RESULTS: In septic animals, cerebral functional capillary density (from 3.1 ± 0.5 to 1.9 ± 0.4 n/mm, p < 0.001) and proportion of small perfused vessels (from 98% ± 2% to 84% ± 7%, p = 0.004) decreased over the 18-hour study period. Concomitantly, PbO2 decreased (61 ± 5 to 41 ± 7 mm Hg, p < 0.001) and lactate/pyruvate ratio increased (23 ± 5 to 36 ± 19, p < 0.001). At 18 hours, when shock was present, animals with a mean arterial pressure less than 65 mm Hg (n = 6) had similar functional capillary density, proportion of small perfused vessels, and PbO2 values but significantly higher lactate/pyruvate ratio (46 ± 18 vs 20 ± 4, p = 0.009) compared with animals with an mean arterial pressure of 65-70 mm Hg (n = 4). CONCLUSIONS: Impaired cerebral microcirculation during sepsis is associated with progressive impairment in PbO2 and brain metabolism. Development of severe hypotension was responsible for a further increase in anaerobic metabolism. These alterations may play an important role in the pathogenesis of brain dysfunction during sepsis.

Living with landslides: Land use on unstable hillslopes in a rural tropical mountainous environment in DR Congo.

Landslides are processes that naturally occur on numerous hillslopes across the world. In inhabited regions, landslides are commonly seen as a threat and a land degradation process. Yet, in densely-populated rural mountainous regions in the tropics, local communities have often no choice but to live on steep terrains naturally impacted by landslides. Besides, landslides may also be a source of opportunities for these communities. However, little is known on the rationale underlying land use in landslides. The aim of this study was to assess the extent, modes of valorization and degree of satisfaction of famers exploiting landslides in a populated rural mountainous environment of DR Congo (territory of Kalehe). We interviewed 82 farmers living on 57 representative landslides, these mass movements having been selected according to their characteristics (size, type) and position along the hillslopes and taking into account accessibility or safety constraints. We show that almost all landslides are being exploited by farmers and that they adapt their land use to the type of landslide. Indeed, significant contrasts are observed between landslides and the surrounding hillslopes for subsistence crops, forests, eucalyptus plantations and pasture. Farmers also adapt land use according to local variations in slope or wetness within a given landslide. Nearly half of the farmers reported that their land was more valuable inside than outside landslides. Better soil fertility, higher soil moisture, lower sand or stone content, lower slopes are some of the main factors that increase the land value, offering more favorable conditions for cropping than on land outside landslides. Despite the perceived risk of landsliding, famers settlement on unstable slopes appears justified by the immediacy of the benefits that outweigh the potential dangers. Better understanding the reasons for the settlement of populations on unstable slopes may help devise better risk reduction strategies.

A next step in adeno-associated virus-mediated gene therapy for neurological diseases: regulation and targeting.

Recombinant adeno-associated virus (rAAV) vectors mediating long term transgene expression are excellent gene therapy tools for chronic neurological diseases. While rAAV2 was the first serotype tested in the clinics, more efficient vectors derived from the rh10 serotype are currently being evaluated and other serotypes are likely to be tested in the near future. In addition, aside from the currently used stereotaxy-guided intraparenchymal delivery, new techniques for global brain transduction (by intravenous or intra-cerebrospinal injections) are very promising. Various strategies for therapeutic gene delivery to the central nervous system have been explored in human clinical trials in the past decade. Canavan disease, a genetic disease caused by an enzymatic deficiency, was the first to be approved. Three gene transfer paradigms for Parkinson's disease have been explored: converting L-dopa into dopamine through AADC gene delivery in the putamen; synthesizing GABA through GAD gene delivery in the overactive subthalamic nucleus and providing neurotrophic support through neurturin gene delivery in the nigro-striatal pathway. These pioneer clinical trials demonstrated the safety and tolerability of rAAV delivery in the human brain at moderate doses. Therapeutic effects however, were modest, emphasizing the need for higher doses of the therapeutic transgene product which could be achieved using more efficient vectors or expression cassettes. This will require re-addressing pharmacological aspects, with attention to which cases require either localized and cell-type specific expression or efficient brain-wide transgene expression, and when it is necessary to modulate or terminate the administration of transgene product. The ongoing development of targeted and regulated rAAV vectors is described.

Brain Tissue Oxygenation-Guided Therapy and Outcome in Traumatic Brain Injury: A Single-Center Matched Cohort Study.

Brain tissue oxygenation (PbtO2)-guided therapy can improve the neurological outcome of traumatic brain injury (TBI) patients. With several Phase-III ongoing studies, most of the existing evidence is based on before-after cohort studies and a phase-II randomized trial. The aim of this study was to assess the effectiveness of PbtO2-guided therapy in a single-center cohort. We performed a retrospective analysis of consecutive severe TBI patients admitted to our center who received either intracranial pressure (ICP) guided therapy (from January 2012 to February 2016) or ICP/PbtO2-guided therapy (February 2017 to December 2019). A genetic matching was performed based on covariates including demographics, comorbidities, and severity scores on admission. Intracranial hypertension (IH) was defined as ICP > 20 mmHg for at least 5 min. Brain hypoxia (BH) was defined as PbtO2 < 20 mmHg for at least 10 min. IH and BH were targeted by specific interventions. Mann−Whitney U and Fisher's exact tests were used to assess differences between groups. A total of 35 patients were matched in both groups: significant differences in the occurrence of IH (ICP 85.7% vs. ICP/PbtO2 45.7%, p < 0.01), ICU length of stay [6 (3−13) vs. 16 (9−25) days, p < 0.01] and Glasgow Coma Scale at ICU discharge [10 (5−14) vs. 13 (11−15), p = 0.036] were found. No significant differences in ICU mortality and Glasgow Outcome Scales at 3 months were observed. This study suggests that the role of ICP/PbtO2-guided therapy should await further confirmation in well-conducted large phase III studies.

Brain tissue oxygenation guided therapy and outcome in non-traumatic subarachnoid hemorrhage.

Brain hypoxia can occur after non-traumatic subarachnoid hemorrhage (SAH), even when levels of intracranial pressure (ICP) remain normal. Brain tissue oxygenation (PbtO2) can be measured as a part of a neurological multimodal neuromonitoring. Low PbtO2 has been associated with poor neurologic recovery. There is scarce data on the impact of PbtO2 guided-therapy on patients' outcome. This single-center cohort study (June 2014-March 2020) included all patients admitted to the ICU after SAH who required multimodal monitoring. Patients with imminent brain death were excluded. Our primary goal was to assess the impact of PbtO2-guided therapy on neurological outcome. Secondary outcome included the association of brain hypoxia with outcome. Of the 163 patients that underwent ICP monitoring, 62 were monitored with PbtO2 and 54 (87%) had at least one episode of brain hypoxia. In patients that required treatment based on neuromonitoring strategies, PbtO2-guided therapy (OR 0.33 [CI 95% 0.12-0.89]) compared to ICP-guided therapy had a protective effect on neurological outcome at 6 months. In this cohort of SAH patients, PbtO2-guided therapy might be associated with improved long-term neurological outcome, only when compared to ICP-guided therapy.

Cerebral microcirculation is impaired during sepsis: an experimental study.

INTRODUCTION: Pathophysiology of brain dysfunction due to sepsis remains poorly understood. Cerebral microcirculatory alterations may play a role; however, experimental data are scarce. This study sought to investigate whether the cerebral microcirculation is altered in a clinically relevant animal model of septic shock. METHODS: Fifteen anesthetized, invasively monitored, and mechanically ventilated female sheep were allocated to a sham procedure (n = 5) or sepsis (n = 10), in which peritonitis was induced by intra-abdominal injection of autologous faeces. Animals were observed until spontaneous death or for a maximum of 20 hours. In addition to global hemodynamic assessment, the microcirculation of the cerebral cortex was evaluated using Sidestream Dark-Field (SDF) videomicroscopy at baseline, 6 hours, 12 hours and at shock onset. At least five images of 20 seconds each from separate areas were recorded at each time point and stored under a random number to be analyzed, using a semi-quantitative method, by an investigator blinded to time and condition. RESULTS: All septic animals developed a hyperdynamic state associated with organ dysfunction and, ultimately, septic shock. In the septic animals, there was a progressive decrease in cerebral total perfused vessel density (from 5.9 ± 0.9 at baseline to 4.8 ± 0.7 n/mm at shock onset, P = 0.009), functional capillary density (from 2.8 ± 0.4 to 2.1 ± 0.7 n/mm, P = 0.049), the proportion of small perfused vessels (from 95 ± 3 to 85 ± 8%, P = 0.02), and the total number of perfused capillaries (from 22.7 ± 2.7 to 17.5 ± 5.2 n/mm, P = 0.04). There were no significant changes in microcirculatory flow index over time. In sham animals, the cerebral microcirculation was unaltered during the study period. CONCLUSIONS: In this model of peritonitis, the cerebral microcirculation was impaired during sepsis, with a significant reduction in perfused small vessels at the onset of septic shock. These alterations may play a role in the pathogenesis of septic encephalopathy.

Early postmortem brain MRI findings in COVID-19 non-survivors.

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to have potential neuroinvasiveness that might lead to acute brain disorders or contribute to respiratory distress in patients with coronavirus disease 2019 (COVID-19). This study investigates the occurrence of structural brain abnormalities in non-survivors of COVID-19 in a virtopsy framework. METHODS: In this prospective, monocentric, case series study, consecutive patients who fulfilled the following inclusion criteria benefited from an early postmortem structural brain MRI: death <24 hours, SARS-CoV-2 detection on nasopharyngeal swab specimen, chest CT scan suggestive of COVID-19, absence of known focal brain lesion, and MRI compatibility. RESULTS: Among the 62 patients who died of COVID-19 from March 31, 2020, to April 24, 2020, at our institution, 19 decedents fulfilled the inclusion criteria. Parenchymal brain abnormalities were observed in 4 decedents: subcortical microbleeds and macrobleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES; 1 decedent), and nonspecific deep white matter changes (1 decedent). Asymmetric olfactory bulbs were found in 4 other decedents without downstream olfactory tract abnormalities. No brainstem MRI signal abnormality was observed. CONCLUSIONS: Postmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19. SARS-CoV-2-related olfactory impairment seems to be limited to olfactory bulbs. Brainstem MRI findings do not support a brain-related contribution to respiratory distress in COVID-19.

The geo-observer network: A proof of concept on participatory sensing of disasters in a remote setting.

Effective disaster risk reduction is often hampered by a general scarcity of reliable data collected on disastrous events, particularly in the Global South. Novel approaches are therefore necessary to alleviate this constraint, particularly with regard to reducing extensive risks. A geo-observer network, consisting of 21 reporters, was established in the Rwenzori region (Uganda) in February 2017 to collect data on eight different disasters using smartphone technology. Within the first 15 months of operation, a total of 319 disaster reports were submitted. A large majority of the reported disasters were reached by the geo-observers within 2 days after their occurrence. The analysis of reporting activity shows a large divergence, with one third of the most active geo-observers accounting for nearly 75% of all reports. By using an existing landslide susceptibility map as a proxy of expected landslide prevalence, this reporting divergence is demonstrated to be at least partially driven by a difference in disaster occurrences. This is confirmed by the results of a survey held among the geo-observers. Survey results also showed that the participants are more driven by non-pecuniary benefits rather than financial compensation. The data collected during the first 15 months of operation indicates that extensive risks in the region are underestimated and demonstrates the added value of participatory sensing to compensate for the current lack of well-functioning official data collection mechanisms. This pilot project is a proof of concept for participatory sensing to collect high quality data even in remote contexts where smartphone technology is not generally adopted. It can serve as a precedent or example for other regions where extensive risks are poorly understood but pose significant threat to the population.

Three-dimensional Gaussian model to define brain metastasis limits on 11C-methionine PET.

PURPOSE: Since 11C-methionine (MET) heavily accumulates in brain tumors, PET with MET (MET-PET) is proposed for the image-guided planning of their targeted therapy. Determination of bulk tumor limits is therefore a crucial component of MET-PET image analysis. We aimed at validating a Gaussian model of tumor delineation on MET-PET. We choose MET-PET and MRI data obtained in brain metastases to adjust the model. Indeed, MRI limits of these non-infiltrative hypermetabolic brain lesions are efficiently used for their curative treatment. METHODS AND MATERIALS: We developed a three-dimensional (3D) Gaussian model that relates the tumor-limit-defining threshold to maximum and mean count values in the defined tumor volume and to mean count values in a reference region. To adjust the model to experimental data, we selected 25 brain metastases following these criteria: (i) no surgery or classical radiotherapy within 6 months, (ii) no previous radiosurgery, (iii) MET-PET and MRI acquired within a 48-h interval, (vi) necrosis representing less than 25% of tumor volume on MRI. We applied a progressive thresholding procedure on MET-PET so as to match tumor limits on contrast-enhanced co-registered MRI. RESULTS: In 22 tumors, a match could be reached between tumor margins on MET-PET and MRI. The relation between mean, maximum and threshold values closely fits the 3D-Gaussian model function. We found a quadratic relation between the mean-to-threshold ratio and the maximum-to-cerebellum activity ratio. CONCLUSIONS: A 3D-Gaussian model may describe the limits of MET uptake distribution within brain metastases, providing a simple method for metabolic tumor delineation.

In vitro evidence of the role of hemoglobin during vasospasm on the modifications of the expression of PKCalpha and zeta.

The cellular events leading to cerebral vasospasm after subarachnoid hemorrhage (SAH) are poorly understood, although the family of protein kinase C (PKC) is already known to play crucial roles in this pathology. Hemoglobin (Hb) is one of the major causes of the cerebral vasospasm that follows SAH. In the present study we investigated whether Hb can in vitro regulate PKC expression in endothelial as opposed to smooth-muscle cells. The levels of expression of PKCalpha and PKCzeta were quantitatively determined by means of computer-assisted fluorescence microscopy in the A7r5 smooth-muscle rat cells and human umbilical endothelial cells (HUVECs). Hb significantly modified both calcium-dependent PKCalpha and calcium-independent PKCzeta expression in HUVECs and A7r5 smooth-muscle rat cells. Our data showed that, in vitro, Hb promptly and markedly modified the levels of expression of both calcium-dependent PKCalpha and calcium-independent PKCzeta. We are currently investigating the effects of specific PKC antagonists associated or not with calcium channel blockers on the expression of PKC and the in vivo severity of SAH-induced vasospasm. Our results encourage the prophylactic use of specific PKC isoform antagonists associated with calcium channel blockers early after SAH to prevent cerebral vasospasm.

Integrated positron emission tomography and magnetic resonance imaging-guided resection of brain tumors: a report of 103 consecutive procedures.

OBJECT: The aim of this study was to evaluate the integration of positron emission tomography (PET) scanning data into the image-guided resection of brain tumors. METHODS: Positron emission tomography scans obtained using fluorine-18 fluorodeoxyglucose (FDG) and L-[methyl-11C]methionine (MET) were combined with magnetic resonance (MR) images in the navigational planning of 103 resections of brain tumors (63 low-grade gliomas [LGGs] and 40 high-grade gliomas [HGGs]). These procedures were performed in 91 patients (57 males and 34 females) in whom tumor boundaries could not be accurately identified on MR images for navigation-based resection. The level and distribution of PET tracer uptake in the tumor were analyzed to define the lesion contours, which in turn yielded a PET volume. The PET scanning-demonstrated lesion volume was subsequently projected onto MR images and compared with MR imaging data (MR volume) to define a final target volume for navigation-based resection-the tumor contours were displayed in the microscope's eyepiece. Maximal tumor resection was accomplished in each case, with the intention of removing the entire area of abnormal metabolic activity visualized during surgical planning. Early postoperative MR imaging and PET scanning studies were performed to assess the quality of tumor resection. Both pre- and postoperative analyses of MR and PET images revealed whether integrating PET data into the navigational planning contributed to improved tumor volume definition and tumor resection. Metabolic information on tumor heterogeneity or extent was useful in planning the surgery. In 83 (80%) of 103 procedures, PET studies contributed to defining a final target volume different from that obtained with MR imaging alone. Furthermore, FDG-PET scanning, which was performed in a majority of HGG cases, showed that PET volume was less extended than the MR volume in 16 of 21 cases and contributed to targeting the resection to the hypermetabolic (anaplastic) area in 11 (69%) of 16 cases. Performed in 59 LGG cases and 23 HGG cases, MET-PET demonstrated that the PET volume did not match the MR volume and improved the tumor volume definition in 52 (88%) of 59 and 18 (78%) of 23, respectively. Total resection of the area of increased PET tracer uptake was achieved in 54 (52%) of 103 procedures. CONCLUSIONS: Imaging guidance with PET scanning provided independent and complementary information that helped to assess tumor extent and plan tumor resection better than with MR imaging guidance alone. The PET scanning guidance could help increase the amount of tumor removed and target image-guided resection to tumor portions that represent the highest evolving potential.

A regulatable AAV vector mediating GDNF biological effects at clinically-approved sub-antimicrobial doxycycline doses.

Preclinical and clinical data stress the importance of pharmacologically-controlling glial cell line-derived neurotrophic factor (GDNF) intracerebral administration to treat PD. The main challenge is finding a combination of a genetic switch and a drug which, when administered at a clinically-approved dose, reaches the brain in sufficient amounts to induce a therapeutic effect. We describe a highly-sensitive doxycycline-inducible adeno-associated virus (AAV) vector. This vector allowed for the first time a longitudinal analysis of inducible transgene expression in the brain using bioluminescence imaging. To evaluate the dose range of GDNF biological activity, the inducible AAV vector (8.0 × 10(9) viral genomes) was injected in the rat striatum at four delivery sites and increasing doxycycline doses administered orally. ERK/Akt signaling activation as well as tyrosine hydroxylase downregulation, a consequence of long-term GDNF treatment, were induced at plasmatic doxycycline concentrations of 140 and 320 ng/ml respectively, which are known not to increase antibiotic-resistant microorganisms in patients. In these conditions, GDNF covered the majority of the striatum. No behavioral abnormalities or weight loss were observed. Motor asymmetry resulting from unilateral GDNF treatment only appeared with a 2.5-fold higher vector and a 13-fold higher inducer doses. Our data suggest that using the herein-described inducible AAV vector, biological effects of GDNF can be obtained in response to sub-antimicrobial doxycycline doses.

Expression of members of the calcium-binding S-100 protein family in a rat model of cerebral basilar artery vasospasm.

OBJECT: The aim of this study was to investigate the role of S-100 proteins in the onset of vasospasm induced by subarachnoid hemorrhage (SAH), which leads to severe neurological morbidity and death. It has recently been argued that modifications in the levels of expression of some intracellular signaling elements controlling the organization of the actin cytoskeleton (including the rho A small guanosine triphosphatase and its related kinases) play significant roles in the induction of smooth-muscle cell contraction, a calcium-dependent process that is pathognomonic of SAH-induced vasospasm at the molecular level. Several members of the calcium-binding S-100 protein family are known to exercise significant control over the organization of the actin cytoskeleton. METHODS: The levels of expression of S-100 proteins in SAH-induced vasospasm have never been investigated. The authors therefore used a double-hemorrhage rat model of SAH-induced vasospasm to determine whether the levels of expression of S-100B, S-100A1, S-100A2, S-100A4, and S-100A6 proteins on immunohistochemical studies were significantly modified in this pathological condition. Quantitative determination of immunohistochemically confirmed expression of S-100 proteins (accomplished with the aid of computer-assisted microscopy) revealed that SAH-induced vasospasm is accompanied by a very significant increase in S-100B, S-100A2, and, to a lesser extent, in S-100A4 and S-100A6 expression, whereas this condition is not accompanied by significant modifications to S-100A1 expression. CONCLUSIONS: Such significant modifications in the levels of expression of different members of the S-100 protein family in SAH-induced vasospasm could relate to the various roles played by this specific class of calcium-binding proteins at the level of actin cytoskeleton organization. These modifications in S-100 protein expression seem relatively specific to SAH-induced vasospasm, because heparin-induced epilepsy-like symptoms were accompanied by dramatically distinct profiles of S-100 protein expression.

Minimally invasive spinal arthrodesis in osteoporotic population using a cannulated and fenestrated augmented screw: technical description and clinical experience.

We describe a percutaneous or minimally invasive approach to apply an augmentation of pedicle fenestrated screws by injection of the PMMA bone cement through the implant and determine the safety and efficiency of this technique in a clinical series of 15 elderly osteoporotic patients. Clinical outcome and the function were assessed using respectively the Visual Analogue Scale (VAS) score and the Oswestry Disability Index (ODI). Peri- and post-operative complications were monitored during a minimum of 2 years of follow-up. Radiographic follow-up was based on plain fluoroscopic control at 3, 6 and 12 months and every year. In this approach, four steps were considered with care: optimal positioning of the screws, correct alignment of the screw heads, waiting time before the injection of cement, fluoroscopic control of the cement injection. Using these precautions, only 2 minor complications occurred. VAS scores and ODI questionnaires showed a statistically significant improvement up to 13.3 months postoperatively. No radiological complications were observed. Based on this experience, PMMA augmentation technique through the novel fenestrated screws provided an effective and long lasting fixation in osteoporotic patients. Applying this procedure through percutaneous or minimally invasive approach under fluoroscopic control seems to be safe.

Management of anterolateral foramen magnum meningiomas: surgical vs conservative decision making.

BACKGROUND: Anterolateral meningiomas of the foramen magnum (FMMs) represent a neurosurgical challenge because they grow in close contact with osteoarticular, nervous, and vascular structures that cannot be sacrificed or retracted. OBJECTIVE: To evaluate our strategy and results in 26 patients with FMMs and analyze factors affecting the decision-making process, resection, and outcome. METHODS: Among 26 consecutive symptomatic FMM (10 anterior, 16 lateral) patients (16 women, 10 men, ages 28-82 years), 4 older than 70 years of age were untreated. Twenty-two were operated on using a posterolateral approach, with the vertebral artery transposed in 19 and the occipital condyle drilled in 10. We analyzed the characteristics and outcome of untreated cases, the utility of THE occipital condyle drilled, the difficulties of microdissection, morbidity and total removal rates, the outcome of tumor residues, and the literature on radiosurgery. RESULTS: Three of 4 untreated patients remained clinically stable at 2 to 5 years. After systematic vertebral artery medial transposition and occipital condyle drilled in 6 cases, our technique evolved with experience in the next 16 (vertebral artery transposed in 13 of 16; occipital condyle drilled in 4 of 13) for dissecting anteriorly beyond midline (anterior FMMs). Retrocondylar access was sufficient for lateral FMMs. Tumors were totally removed in 16 of 22 (73%). One patient died, and 4 had permanent deficits. Follow-up of more than 5 years in 12 patients showed no C0-1 instability, and slight increase of tumor residue size 7 years after surgery. In the literature, 15 FMMs treated with radiosurgery are reported, 13 at diagnosis and 2 at recurrence, with short-term clinical and radiological safety and efficacy. CONCLUSION: We currently recommend (1) aiming for subtotal removal in difficult cases, (2) remaining conservative in asymptomatic or elderly patients with mild symptoms, and (3) considering radiosurgery at diagnosis for small (<30 mm) symptomatic FMMs or as an adjunct for evolving residues/recurrences in poor candidates for resection.

Positron emission tomography-guided volumetric resection of supratentorial high-grade gliomas: a survival analysis in 66 consecutive patients.

OBJECTIVE: Integrating positron emission tomographic (PET) images into the image-guided resection of high-grade gliomas (HGG) has shown that metabolic information on tumor heterogeneity and distribution are useful for planning surgery, improve tumor delineation, and provide a final target contour different from that obtained with magnetic resonance imaging (MRI) alone in about 80% of the procedures. Moreover, PET guidance helps to increase the amount of tumor removed and to target image-guided resection to anaplastic tissue areas. The present study aims to evaluate whether PET-guided volumetric resection (VR) in supratentorial HGG might add benefit to the patient's outcome. METHODS: PET images using [18F]fluorodeoxyglucose (n=23) and [11C]methionine (n=43) were combined with MRI scans in the planning of VR procedures performed at the initial stage in 66 consecutive patients (43 M/23 F) with supratentorial HGG according to the technique previously described. In all cases (35 anaplastic gliomas [20 astrocytomas, 10 oligoastrocytomas, 5 oligodendrogliomas] and 31 glioblastomas [GBM]), level and distribution of PET tracer uptake were analyzed to define a PET contour projected on MRI scans to define a final target contour for VR. Maximal tumor resection was accomplished in each case, with the intention to remove the entire abnormal metabolic area comprised in the surgical planning. Early postoperative MRI and PET assessed tumor resection. Survival analysis was performed separately in anaplastic gliomas and glioblastoma multiforme according to the presence or absence of residual tracer uptake on postoperative PET and according to the presence or absence of residual contrast enhancement on postoperative MRI. RESULTS: Preoperatively, metabolic information helped the surgical planning. In all procedures, PET contributed to define a final target contour different from that obtained with MRI alone. Postoperatively, 46 of 66 patients had no residual PET tracer uptake (total PET resection), 23 of 66 had no residual MRI contrast enhancement. No additional neurological morbidity due to the technique was reported. A total PET tracer uptake resection was associated with a significantly longer survival in anaplastic gliomas (P = 0.0071) and in glioblastoma multiforme (P = 0.0001), respectively. A total MRI contrast enhancement resection was not correlated with a significantly better survival, neither in anaplastic gliomas (P = 0.6089) nor in glioblastoma multiforme (P = 0.6806). CONCLUSIONS: Complete resection of the increased PET tracer uptake prolongs the survival of HGG patients. Because PET information represents a more specific marker than MRI enhancement for detecting anaplastic tumor tissue, PET-guidance increases the amount of anaplastic tissue removed in HGG.