Towards individualised and optimalised positioning of non-ventilated COVID-19 patients: Putting the affected parts of the lung(s) on top?

The outbreak of COVID-19 led to an unprecedented inflow of hospitalised patients with severe acute respiratory syndrome (SARS), requiring high-flow non-invasive oxygenation, if not invasive mechanical ventilation. While the best option in terms of non-invasive systems of oxygen delivery is still a matter of debate, it also remains unclear as to whether or not the optimal in-bed positioning of patients might also help to improve their oxygen saturation levels. On the basis of three representative cases, it is possible to propose the following hypotheses: (i) how patients are positioned has a strong influence on their oxygen saturation levels; (ii) saturation-optimalised positions are patient-specific; (iii) prone positions require ergonomic devices; and (iv) saturation-optimalised positions should aim to place the most affected part(s) of the lung(s) on top. Considered together, these hypotheses have led us to recommend that COVID-19 patients should undergo a specific assessment at admission to determine their saturation-optimalised in-bed position. However, further studies are still needed to assess the benefits of such a strategy on clinical outcomes.

Measuring the electrophysiological effects of direct electrical stimulation after awake brain surgery.

OBJECTIVE: Direct electrical stimulation (DES) at 60 Hz is used to perform real-time functional mapping of the brain, and guide tumour resection during awake neurosurgery. Nonetheless, the electrophysiological effects of DES remain largely unknown, both locally and remotely. APPROACH: In this study, we lowered the DES frequency to 1-10 Hz and we used a differential recording mode of electro-corticographic (ECoG) signals to improve the focality with a simple algorithm to remove the artefacts due to the response of the acquisition chain. MAIN RESULTS: Doing so, we were able to observe different components in the evoked potentials triggered by simulating the cortex or the subcortical white matter pathways near the recording electrodes and by stimulating the cortex remotely from the recording site. More particularly, P0 and N1 components were repeatedly observed on raw ECoG signals without the need to average the data. SIGNIFICANCE: This new methodology is important to probe the electrophysiological states and the connectivity of the brain in vivo and in real time, namely to perform electrophysiological brain mapping on human patients operated in the neurosurgical room and to better understand the electrophysiological spreading of DES.

Angiotensin II receptor blockers, steroids and radiotherapy in glioblastoma-a randomised multicentre trial (ASTER trial). An ANOCEF study.

BACKGROUND: Glioblastomas (GBMs) induce a peritumoural vasogenic oedema impairing functional status and quality of life. Steroids reduce brain tumour-related oedema but are associated with numerous side-effects. It was reported in a retrospective series that angiotensin receptor blockers might be associated with reduced peritumoural oedema. The ASTER study is a randomised, placebo-controlled trial to assess whether or not the addition of Losartan to standard of care (SOC) can reduce steroid requirement during radiotherapy (RT) in patients with newly diagnosed GBM. PATIENTS AND METHODS: Patients with a histologically confirmed GBM after biopsy or partial surgical resection were randomised between Losartan or placebo in addition to SOC with RT and temozolomide (TMZ). The primary objective was to investigate the steroid dosage required to control brain oedema on the last day of RT in each arm. The secondary outcomes were steroids dosage 1 month after the end of RT, assessment of cerebral oedema on magnetic resonance imaging, tolerance and survival. RESULTS: Seventy-five patients were randomly assigned to receive Losartan (37 patients) or placebo (38 patients). No difference in the steroid dosage required to control brain oedema on the last day of RT, or one month after completion of RT, was seen between both arms. The incidence of adverse events was similar in both arms. Median overall survival was similar in both arms. CONCLUSIONS: Losartan, although well tolerated, does not reduce the steroid requirement in newly diagnosed GBM patients treated with concomitant RT and TMZ. Trial registration number NCT01805453 with ClinicalTrials.gov.

A network-level approach of cognitive flexibility impairment after surgery of a right temporo-parietal glioma.

OBJECTIVE: The right "non-dominant" temporo-parietal junction is usually not considered as a highly eloquent area. This contrasts with its mirrored left "dominant" counterpart, which is known as highly eloquent regarding language function. The question arises about which functions should be monitored when operating lesions of the right temporo-parietal junction under awake conditions. METHODS: We report the case of a patient who underwent a surgical resection of a glioma located in the right temporo-parietal junction. Cognitive evaluations were performed preoperatively and 4 months after surgery, as well as resting state fMRI and diffusion-based tractography. RESULTS: Long-term postoperative cognitive examination revealed an important deterioration of cognitive control abilities, especially regarding set-shifting abilities as measured by Trail making test part B. Based on pre- and postoperative resting state fMRI and diffusion-based tractography, we demonstrate that surgical resection massively impacted structural and functional connectivity of the right fronto-parieto-temporal network, a network that is classically involved in cognitive control, reasoning and working memory. CONCLUSION: This case clearly illustrates how a white matter focal lesion can generate a neuropsychological deficit by remotely disconnecting distant cortical areas belonging to a functional network. Furthermore, our observation strongly supports the use of intraoperative cognitive control tests during surgery of the right temporo-parietal junction and promote the interest of pre and postoperative resting state functional connectivity to explore the potential mechanisms causing cognitive deficits.

Resection of cavernous angioma located in eloquent areas using functional cortical and subcortical mapping under awake conditions. Outcomes in a 50-case multicentre series.

INTRODUCTION: Surgical resection of supratentorial cavernous angiomas located in eloquent areas poses a significant risk to the patient of postoperative neurological impairment and justifies intraoperative functional monitoring. METHODS: Multicentre retrospective series of adult patients with cavernous angiomas located within eloquent areas and treated with functional-based surgical resection according to functional boundaries under intraoperative functional cortico-subcortical monitoring under awake conditions. RESULTS: Fifty patients (18 males, mean 36.3±10.8 year-old) underwent surgical resection with intraoperative cortico-subcortical functional mapping using direct electrostimulation under awake conditions for a cavernous angioma located in eloquent areas with a mean postoperative follow-up of 21.0±21.2 months. At presentation, the cavernous angioma had previously resulted in severe impairment (neurological deficit in 34%, seizures in 70%, uncontrolled seizures in 34%, reduced Karnofsky Performance Status score of 70 or less in 24%, inability to work in 52%). Functional-based surgical resection allowed complete removal of the cavernous angioma in 98% and of the haemosiderin rim in 82%. Postoperative seizures and other complications were rare, and similarly so across all centres included in this series. Postoperatively, we found functional improvement in 84% of patients (reduced Karnofsky Performance Status score of 70 or less in 6%, uncontrolled seizures in 16%, and inability to work in 11%). CONCLUSION: Functional-based surgical resection aids the safe and complete resection of cavernous angiomas located in eloquent areas while minimizing the surgical risks. Functional mapping has to be considered in such challenging cases.

Technical principles of direct bipolar electrostimulation for cortical and subcortical mapping in awake craniotomy.

INTRODUCTION: Intraoperative application of electrical current to the brain is a standard technique during brain surgery for inferring the function of the underlying brain. The purpose of intraoperative functional mapping is to reliably identify cortical areas and subcortical pathways involved in eloquent functions, especially motor, sensory, language and cognitive functions. MATERIAL AND METHODS: The aim of this article is to review the rationale and the electrophysiological principles of the use of direct bipolar electrostimulation for cortical and subcortical mapping under awake conditions. RESULTS: Direct electrical stimulation is a window into the whole functional network that sustains a particular function. It is an accurate (spatial resolution of about 5mm) and a reproducible technique particularly adapted to clinical practice for brain resection in eloquent areas. If the procedure is rigorously applied, the sensitivity of direct electrical stimulation for the detection of cortical and subcortical eloquent areas is nearly 100%. The main disadvantage of this technique is its suboptimal specificity. Another limitation is the identification of eloquent areas during surgery, which, however, could have been functionally compensated postoperatively if removed surgically. CONCLUSION: Direct electrical stimulation is an easy, accurate, reliable and safe invasive technique for the intraoperative detection of both cortical and subcortical functional brain connectivity for clinical purpose. In our opinion, it is the optimal technique for minimizing the risk of neurological sequelae when resecting in eloquent brain areas.

A surgical approach to the anatomo-functional structure of language.

INTRODUCTION: Language is the most widely mapped cognitive function during brain surgery. Intraoperative language functional mapping using direct electrical stimulation under awake conditions is currently the gold standard technique for establishing the causal link between an area and a deficit that would be caused by its resection. It is also a powerful tool to investigate the anatomical correlates of current neuropsychological models of language. MATERIAL AND METHODS: The aim of this article is to reexamine the anatomo-functional structure of language that could be inferred from data obtained in direct electrical stimulation studies during awake surgery. RESULTS: Concomitantly with the development of new neuropsychological models of language, major advances have been made in our understanding of error patterns elicited by language network stimulation, both cortically and axonally. Following the recognition of visual information, the language network of picture naming is organized in parallel into two main dorsal phonological and ventral semantic subsystems that are sustained anatomically by two systems (arcuate fasciculus and inferior fronto-occipital/inferior longitudinal/uncinate fasciculus respectively). Networks of articulatory and motor aspects of speech are now better depicted (aslant tract, third branch of longitudinal fasciculus). Finally, the links between the core language networks and the cognitive control networks are also emerging. CONCLUSION: Mastering the language map and its dynamical properties should be a basic prerequisite for any neurosurgeon who wishes to operate on the brain with the aim of optimizing the extent of resection while preserving language abilities.

Axono-cortical evoked potentials: A proof-of-concept study.

Awake surgery is currently considered the best method to tailor intraparenchymatous resections according to functional boundaries. However, the exact mechanisms by which electrical stimulation disturbs behavior remain largely unknown. In this case report, we describe a new method to explore the propagation toward cortical sites of a brief pulse applied to an eloquent white matter pathway. We present a patient, operated on in awake condition for removal of a cavernoma of the left ventral premotor cortex. At the end of the resection, the application of 60Hz stimulation in the white matter of the operculum induced anomia. Stimulating the same site at a frequency of 1Hz during 70seconds allowed to record responses on electrodes put over Broca's area and around the inferior part of central sulcus. Axono-cortical evoked potentials were then obtained by averaging unitary responses, time-locked to the stimulus. We then discuss the origin of these evoked axono-cortical potentials and the likely pathway connecting the stimulation site to the recorded cortical sites.

[Surgery of brain metastases]. / Place de la chirurgie dans la prise en charge des métastases cérébrales.

Surgical excision of brain metastases has been well evaluated in unique metastases. Two randomized phase III trial have shown that combined with adjuvant whole brain radiotherapy, it significantly improves overall survival. However, even in the presence of multiple brain metastases, surgery may be useful. Also, even in lesions amenable to radiosurgery, surgical resection is preferred when tumors displayed cystic or necrotic aspect with important edema or when located in highly eloquent areas or cortico-subcortically. Furthermore, surgery may have a diagnostic role, in the absence of histological documentation of the primary disease, to rule out a differential diagnosis (brain abscess, lymphoma, primary tumor of the central nervous system or radionecrosis). Finally, the biological documentation of brain metastatic disease might be useful in situations where a specific targeted therapy can be proposed. Selection of patients who will really benefit from surgery should take into account three factors, clinical and functional status of the patient, systemic disease status and characteristics of intracranial metastases. Given the improved overall survival of cancer patients partially due to the advent of effective targeted therapies on systemic disease, a renewed interest has been given to the local treatment of brain metastases. Surgical resection currently represents a valuable tool in the armamentarium of brain metastases but has also become a diagnostic and decision tool that can affect therapeutic strategies in these patients.

[ANOCEF guidelines for the management of brain metastases]. / Recommandations de l'Anocef pour la prise en charge des métastases cérébrales.

The incidence of brain metastases is increasing because of the use of new therapeutic agents, which allow an improvement of overall survival, but with only a poor penetration into the central nervous system brain barriers. The management of brain metastases has changed due to a better knowledge of immunohistochemical data and molecular biological data, the development of new surgical, radiotherapeutic approaches and improvement of systemic treatments. Most of the time, the prognosis is still limited to several months, nevertheless, prolonged survival may be now observed in some sub-groups of patients. The main prognostic factors include the type and subtype of the primitive, age, general status of the patient, number and location of brain metastases, extracerebral disease. The multidisciplinary discussion should take into account all of these parameters. We should notice also that treatments including surgery or radiotherapy may be proposed in a symptomatic goal in advanced phases of the disease underlying the multidisciplinary approach until late in the evolution of the disease. This article reports on the ANOCEF (French neuro-oncology association) guidelines. The management of brain metastases of breast cancers and lung cancers are discussed in the same chapter, while the management of melanoma brain metastases is reported in a separate chapter due to different responses to the brain radiotherapy.

Expert-validated CSF segmentation of MNI atlas enhances accuracy of virtual glioma growth patterns.

Biomathematical modeling of glioma growth has been developed to optimize treatments delivery and to evaluate their efficacy. Simulations currently make use of anatomical knowledge from standard MRI atlases. For example, cerebrospinal fluid (CSF) spaces are obtained by automatic thresholding of the MNI atlas, leading to an approximate representation of real anatomy. To correct such inaccuracies, an expert-revised CSF segmentation map of the MNI atlas was built. Several virtual glioma growth patterns of different locations were generated, with and without using the expert-revised version of the MNI atlas. The adequacy between virtual and radiologically observed growth patterns was clearly higher when simulations were based on the expert-revised atlas. This work emphasizes the need for close collaboration between clinicians and researchers in the field of brain tumor modeling.

[Chordoma]. / Les chordomes.

PURPOSES: To review in the literature, all the epidemiological, clinical, radiological, histological and therapeutic data regarding chordomas as well as various notochordal entities: ecchordosis physaliphora, intradural and intraparenchymatous chordomas, benign notochordal cell tumors, parachordomas and extra-axial chordomas. To identify different types of chordomas, including familial forms, associations with tuberous sclerosis, Ollier's disease and Maffucci's syndrome, forms with metastasis and seeding. To assess the recent data regarding molecular biology and progress in targeted therapy. To compare the different types of radiotherapy, especially protontherapy and their therapeutic effects. To review the largest series of chordomas in their different localizations (skull base, sacrum and mobile spine) from the literature. MATERIALS: The series of 136 chordomas treated and followed up over 20 years (1972-2012) in the department of neurosurgery at Lariboisière hospital is reviewed. It includes: 58 chordomas of the skull base, 47 of the craniocervical junction, 23 of the cervical spine and 8 from the lombosacral region. Similarly, 31 chordomas in children (less than 18 years of age), observed in the departments of neurosurgery of les Enfants-Malades and Lariboisière hospitals, are presented. They were observed between 1976 and 2010 and were located intracranially (n=22 including 13 with cervical extension), 4 at the craniocervical junction level and 5 in the cervical spine. METHODS: In the entire Lariboisière series and in the different groups of localization, different parameters were analyzed: the delay of diagnosis, of follow-up, of occurrence of metastasis, recurrence and death, the number of primary patients and patients referred to us after progression or recurrence and the number of deaths, recurrences and metastases. The influence of the quality of resection (total, subtotal and partial) on the prognosis is also presented. Kaplan-Meier actuarial curves of overall survival and disease free survival were performed in the entire series, including the different groups of localization based on the following 4 parameters: age, primary and secondary patients, quality of resection and protontherapy. In the pediatric series, a similar analysis was carried-out but was limited by the small number of patients in the subgroups. RESULTS: In the Lariboisière series, the mean delay of diagnosis is 10 months and the mean follow-up is 80 months in each group. The delay before recurrence, metastasis and death is always better for the skull base chordomas and worse for those of the craniocervical junction, which have similar results to those of the cervical spine. Similar figures were observed as regards the number of deaths, metastases and recurrences. Quality of resection is the major factor of prognosis with 20.5 % of deaths and 28 % of recurrences after total resection as compared to 52.5 % and 47.5 % after subtotal resection. This is still more obvious in the group of skull base chordomas. Adding protontherapy to a total resection can still improve the results but there is no change after subtotal resection. The actuarial curve of overall survival shows a clear cut in the slope with some chordomas having a fast evolution towards recurrence and death in less than 4 years and others having a long survival of sometimes more than 20 years. Also, age has no influence on the prognosis. In primary patients, disease free survival is better than in secondary patients but not in overall survival. Protontherapy only improves the overall survival in the entire series and in the skull base group. Total resection improves both the overall and disease free survival in each group. Finally, the adjunct of protontherapy after total resection is clearly demonstrated. In the pediatric series, the median follow-up is 5.7 years. Overall survival and disease free survival are respectively 63 % and 54.3 %. Factors of prognosis are the histological type (atypical forms), localization (worse for the cervical spine and better for the clivus) and again it will depend on the quality of resection. CONCLUSIONS: Many different pathologies derived from the notochord can be observed: some are remnants, some may be precursors of chordomas and some have similar features but are probably not genuine chordomas. To-day, immuno-histological studies should permit to differentiate them from real chordomas. Improving knowledge of molecular biology raises hopes for complementary treatments but to date the quality of surgical resection is still the main factor of prognosis. Complementary protontherapy seems useful, especially in skull base chordomas, which have better overall results than those of the craniocervical junction and of the cervical spine. However, we are still lacking an intrinsic marker of evolution to differentiate the slow growing chordomas with an indolent evolution from aggressive types leading rapidly to recurrence and death on which more aggressive treatments should be applied.

Functionally tailored transcortical approach of deep-seated lesions: an alternative to the transulcal approach? a technical case report.

It is commonly believed that sulci offer a natural path to reach deep-seated lesions. However, it has also been argued that this approach carries a risk of damaging the vessels during the opening of the sulcus.We therefore were prompted to test the possibility of finding a transcortical path identified as non-functional by intraoperative brain mapping. A successful resection is presented of a left posterior is thmusclear cell ependymoma through a selected corridor based on functional mapping in an awake patient.MRI performed at 12 months showed no tumour recurrence. Pre- and postoperative extensive testing confirmed an improvement of the patient's cognitive functions. Therefore, we were able to demonstrate the feasibility of a functionally tailored transcortical approach as an alternative to the transulcal approach for deep-seated lesions. This concept should be validated in a larger patient series.

The importance of measuring the velocity of diameter expansion on MRI in upfront management of suspected WHO grade II glioma - case report.

A right insular lesion was incidentally discovered in a 48-year-old male. Morphological and metabolic radiological characteristics on magnetic resonance imaging (MRI) were in favor of a World Health Organization (WHO) grade II glioma. Despite being advised that surgery was appropriate, the patient elected for conservative management. A second MRI was performed 5 months after, and interpreted as unchanged. A third MRI 4 months later demonstrated a significant increase in tumor size and enhancement in a new distant tumor focus. The patient was referred to our center and underwent surgical resection. Histopathology revealed a grade III astrocytoma. A retrospective quantitative measurement of the radiological growth between the two first MRIs yielded a growth rate of 12 mm/year. This value, highly suggestive of a malignant glioma, should have triggered surgery at the time of the second MRI. We conclude that, whenever surgical treatment of a suspected WHO grade II gliomas is postponed, assessing tumor kinetics quantitatively is important to identify patients whose tumor is indeed a WHO grade III glioma. The tumor should be indeed followed by serial MRIs with quantitative measurement of tumor growth, not just "eyeball" qualitative examination. Immediate treatment is indicated in patients with radiological tumor expansion of greater than 8mm/year.

Endoscopic endonasal skull base surgery.

Skull base surgery has been transformed by the development of endoscopic techniques. Endoscopic procedures were first used for pituitary surgery and were then gradually extended to other regions. A wide range of diseases are now accessible to endoscopic skull base surgery. The major advantage of the endoscopic endonasal approach is that it provides direct anatomical access to a large number of intracranial and paranasal sinus lesions, avoiding the sequelae of a skin incision, facial bone flap or craniotomy, and brain retraction, which is inevitable with conventional neurosurgical incisions, resulting in decreased morbidity and mortality and, indirectly, decreased length of hospital stay and management costs. Moreover, the increasing number of publications in this field illustrates the growing interest in these techniques. This paper provides a review of endoscopic skull base surgery. The indications and general principles of endoscopic endonasal skull base surgery are described. Progress in exposure and especially reconstruction techniques is described. This progress now allows more extensive resections, while maintaining acceptable morbidity. The limits of this surgery are also discussed; in particular, although this surgery is often described as "minimally invasive", it is not completely devoid of morbidity.

Improving the time-machine: estimating date of birth of grade II gliomas.

OBJECTIVES: Here we present a model aiming to provide an estimate of time from tumour genesis, for grade II gliomas. The model is based on a differential equation describing the diffusion-proliferation process. We have applied our model to situations where tumour diameter was shown to increase linearly with time, with characteristic diametric velocity. MATERIALS AND METHODS: We have performed numerical simulations to analyse data, on patients with grade II gliomas and to extract information concerning time of tumour biological onset, as well as radiology and distribution of model parameters. RESULTS AND CONCLUSIONS: We show that the estimate of tumour onset obtained from extrapolation using a constant velocity assumption, always underestimates biological tumour age, and that the correction one should add to this estimate is given roughly by 20/v (year), where v is the diametric velocity of expansion of the tumour (expressed in mm/year). Within the assumptions of the model, we have identified two types of tumour: the first corresponds to very slowly growing tumours that appear during adolescence, and the second type corresponds to slowly growing tumours that appear later, during early adulthood. That all these tumours become detectable around a mean patient age of 30 years could be interesting for formulation of strategies for early detection of tumours.

Mathematical modeling of glioma on MRI.

The advent of Magnetic Resonance Imaging (MRI) has enabled quantification of glioma growth with millimetric accuracy. Thus, it is now possible to monitor the growth curve of tumor diameter for each patient. Mathematical modeling contributes to the analysis of these curves and to determining individual parameters characterizing tumor dynamics. We will focus on the most studied model, based on a proliferation-diffusion equation. We will review how this approach, when applied to low-grade gliomas, has enabled defining a new way to quantify their natural history, leading to the inclusion of tumor kinetics among prognostic factors. Finally, quantitative imaging coupled with mathematical modeling is opening new avenues in our understanding of treatment effects, allowing to optimize therapeutic strategies for gliomas in the near future.

Transient symptomatic vasospasm following antero-mesial temporal lobectomy for refractory epilepsy.

RATIONALE: Arterial vasospasm has rarely been reported following temporal lobectomy for intractable epilepsy. CASE PRESENTATION: A 31-year-old patient presented with a global aphasia 2 days after a left dominant anteromesial temporal lobectomy for intractable epilepsy. Magnetic resonance imaging on 5th post-operative day revealed severe narrowing of M1 segment of the left middle cerebral artery (MCA) and Transcranial Doppler (TCD) ultrasonography an increased velocity of the MCA that suggested a severe vasospasm. The patient received continuous intravenous hyperhydratation and nimodipine; aphasia improved within 24 h and resolved completely within 6 weeks, associated with velocity reduction on control TCD. CONCLUSION: Transient vasospasm is a likely underestimated cause of focal deficit following temporomesial resection that deserves appropriate treatment.