Cold sensing by NaV1.8-positive and NaV1.8-negative sensory neurons.

The ability to detect environmental cold serves as an important survival tool. The sodium channels NaV1.8 and NaV1.9, as well as the TRP channel Trpm8, have been shown to contribute to cold sensation in mice. Surprisingly, transcriptional profiling shows that NaV1.8/NaV1.9 and Trpm8 are expressed in nonoverlapping neuronal populations. Here we have used in vivo GCaMP3 imaging to identify cold-sensing populations of sensory neurons in live mice. We find that ∼80% of neurons responsive to cold down to 1 °C do not express NaV1.8, and that the genetic deletion of NaV1.8 does not affect the relative number, distribution, or maximal response of cold-sensitive neurons. Furthermore, the deletion of NaV1.8 had no observable effect on transient cold-induced (≥5 °C) behaviors in mice, as measured by the cold-plantar, cold-plate (5 and 10 °C), or acetone tests. In contrast, nocifensive-like behavior to extreme cold-plate stimulation (-5 °C) was completely absent in mice lacking NaV1.8. Fluorescence-activated cell sorting (FACS) and subsequent microarray analysis of sensory neurons activated at 4 °C identified an enriched repertoire of ion channels, which include the Trp channel Trpm8 and potassium channel Kcnk9, that are potentially required for cold sensing above freezing temperatures in mouse DRG neurons. These data demonstrate the complexity of cold-sensing mechanisms in mouse sensory neurons, revealing a principal role for NaV1.8-negative neurons in sensing both innocuous and acute noxious cooling down to 1 °C, while NaV1.8-positive neurons are likely responsible for the transduction of prolonged extreme cold temperatures, where tissue damage causes pan-nociceptor activation.

Syringomyelia and hydromyelia: Current understanding and neurosurgical management.

Syringomyelia is a rare disorder in which a fluid-filled cyst forms within the spinal cord, resulting in myelopathy. Meanwhile, the abnormal dilatation of the central canal is referred to as hydromyelia or slit-like syrinx. The most prevailing classification is based on anatomical features and pathogeny rather than pathophysiological mechanisms. It is usual to distinguish foraminal syringomyelia related mainly to abnormalities at the craniocervical junction, non-foraminal syringomyelia dealing with any cause of arachnoiditis (infection, inflammation, trauma…) and more rarely syringomyelia associated with intramedullary tumors. Although many pathophysiological theories have been argued over time, the prevailing one is that disturbances in cerebrospinal fluid (CSF) flow in the sub-arachnoid spaces disrupt flow velocity leading to the syrinx. Symptoms of paralysis, sensory loss and chronic pain commonly develop during the third/fourth decades of life. The natural history of syringomyelia is typically one of gradual, stepwise neurological deterioration extending over many years. Diagnosis is based on magnetic resonance imaging (MRI) including excellent morphological sequences (T1-, T2-, FLAIR-, T2*-, enhanced T1-) and dynamic MRI with careful study of CSF velocity (CISS, cine-MR sequences). Surgical management is at first dedicated to treat the cause of the syringomyelia, mainly to re-establish a physiological CSF pathway in the subarachnoid spaces. Mostly, the surgical goal is to enlarge the craniocervical junction with duraplasty. Other surgical strategies such as arachnoidolysis or shunt procedures are performed based on the pathogenic mechanisms or as second-line treatment. Medical treatments are also necessary as chronic pain is the main long-lasting symptom. As evolutive syringomyelia is a severe disease with a high impact on quality of life, it is recommended to treat without delay. There is no evidence for surgery for incidental asymptomatic syringomyelia or hydromyelia. Finally, syringomyelia associated with intramedullary tumors resolves spontaneously after tumor resection. Syringomyelia is a rare disease, which requires a dedicated multidisciplinary approach, emphasizing the need for a nationwide scientific organization so as to offer optimal care to the patient.

Adult brainstem glioma presenting with isolated persistent hemifacial spasm or facial nerve palsy.

OBJECT: Adult brainstem gliomas are a rare group of heterogeneous brain tumors. Classical clinical presentation includes progressive impairment of cranial nerves associated with long tract signs. The prognosis and response to treatment are poor; nevertheless, some patients do have a long survival. The objective of this study was to describe a series of patients with an isolated persistent hemifacial spasm and/or facial nerve palsy as the presenting symptom of a brainstem glioma. METHODS: Fourteen patients from 3 French hospitals (Paris, Caen, Lille) were included. Clinical and radiological features and overall survival were retrospectively analyzed. A review of the literature of similar cases was performed. RESULTS: Mean age at diagnosis was 35 years (range 19-57 years). Mean duration of facial nerve involvement before diagnosis was 17 months (range 1-48 months). Tumors were characterized on MRI by a lateralized location in the pons, a T1-weighted hyposignal, a T2-weighted hypersignal and no contrast enhancement after Gadolinium injection except for 2 cases. Biopsies were performed in 10 cases and showed 8 low-grade and 2 high-grade gliomas. All the patients were initially treated with radiotherapy and 6 patients with chemotherapy after progression. Eleven patients died from tumor progression. Median survival time was 90 months. CONCLUSIONS: Adult brainstem gliomas revealed by a progressive isolated involvement of the facial nerve seem to have particular clinico-radiological features of slow progressive tumors and may be associated with long patient survival.

Epilepsy and restless legs syndrome.

OBJECTIVE: Restless legs syndrome (RLS) is a common neurological movement disorder occurring in approximately 10% of the general population. The prevalence of moderately severe RLS is 2.7% overall (3.7% for women and 1.7% for men). Epilepsy is also a common neurological disorder with significant associated morbidity and impact on quality of life. We evaluated the severity and frequency of primary RLS in patients with localization-related temporal lobe epilepsy (TLE) and investigated the role of prodromal RLS symptoms as a warning sign and lateralizing indicator. METHODS: All epilepsy patients seen in the outpatient clinic were screened for movement disorders from 2005 to 2015. Ninety-eight consecutive patients with localization-related TLE (50 right TLE and 48 left TLE) who met inclusion criteria were seen in the outpatient clinic. The control group consisted of 50 individuals with no history or immediate family history of epilepsy. Each patient was evaluated with the International Restless Legs Study Group (IRLSSG) questionnaire, NIH RLS diagnostic criteria, ferritin level, and comprehensive sleep screening including polysomnography. Furthermore, patients with obstructive sleep apnea or a definite cause of secondary restless legs syndrome such as low serum ferritin or serum iron levels were also excluded from the study. RESULTS: There was a significant association between the type of epilepsy and whether or not patients had RLS χ2 (1)=10.17, p<.01, using the χ2 Goodness of Fit Test. Based on the odds ratio, the odds of patients having RLS were 4.60 times higher if they had right temporal epilepsy than if they had left temporal epilepsy, serving as a potential lateralizing indicator. A prodromal sensation of worsening RLS occurred in some patients providing the opportunity to intervene at an earlier stage in this subgroup. SIGNIFICANCE: We identified frequent moderate to severe RLS in patients with epilepsy. The frequency of RLS was much more common than would typically be seen in patients of similar age. The restlessness was typically described as moderately severe. The RLS symptoms were more common and somewhat more severe in the right TLE group than the left TLE group.

Impact of Covid-19 pandemic on neuro-oncology multidisciplinary tumor board in the pre-vaccine era: the Normandy experience.

INTRODUCTION: The COVID19 pandemic had a strong impact on the healthcare system, particularly in oncology. Brain tumor are usually revealed by acute and life threatening symptoms. We wanted to evaluate the possible consequences of the COVID19 pandemic in 2020 on the activity of neuro-oncology multidisciplinary tumor board in a Normandy region (France). METHODS: A descriptive, retrospective, multicenter study was conducted in the four referent centers (two universitary hospitals and two cancer centers). The main objective was to compare the average number of neuro-oncology patients presented per multidisciplinary tumor board per week between a pre-COVID19 reference period (period 1 from December 2018 to December 2019) and the pre-vaccination period (period 2 from December 2019 to November 2020). RESULTS: Across Normandy, 1540 cases were presented in neuro-oncology multidisciplinary tumor board in 2019 and 2020. No difference was observed between period 1 and 2: respectively 9.8 per week versus 10.7, P=0.36. The number of cases per week also did not significantly differ during the lockdown periods: 9.1/week versus 10.4 during the non-lockdown periods, P=0.26. The only difference observed was a higher proportion of tumor resection during the lockdown periods: 81.4% (n=79/174) versus 64.5% (n=408/1366), P=0.001. CONCLUSION: The pre-vaccination era of the COVID19 pandemic did not impact the activity of neuro-oncology multidisciplinary tumor board in the Normandy region. The possible consequences in terms of public health (excess mortality) due to this tumor location should now be investigated.

An updated model of hydrocephalus in sheep to evaluate the performance of a device for ambulatory wireless monitoring of cerebral pressure through shunts.

BACKGROUND: Cerebrospinal fluid (CSF) diversion by shunts is the most common surgical treatment for hydrocephalus. Though effective, shunts are associated with risk of dysfunction leading to multiple surgical revisions, affecting patient quality-of-life and incurring high healthcare costs. There is a need for ambulatory monitoring systems for life-long assessment of shunt status. The present study aimed to develop a preclinical model assessing the feasibility of our wireless device for continuous monitoring of cerebral pressure in shunts. METHODS: We first adapted a previous hydrocephalus model in sheep, which used an intracisternal kaolin injection. Seven animals were used to establish the model, and 1 sheep with naturally dilated ventricles was used as control. Hydrocephalus was confirmed by clinical examination and brain imaging before inserting the ventriculoperitoneal shunts and the monitoring device allowing continuous measurement of the pressure through the shunt for a few days in 3 sheep. An external ventricular drain was used as gold standard. RESULTS: Our results showed that a reduction in kaolin dose associated to postoperative management was crucial to reduce morbidity and mortality rates in the model. Ventriculomegaly was confirmed by imaging 4 days after injection of 75mg kaolin into the cisterna magna. For the implanted sheep, recordings revealed high sensitivity of our sensor in detecting fluctuations in cerebral pressure compared to conventional measurements. CONCLUSIONS: This proof-of-concept study highlights the potential of this preclinical model for testing new shunt devices.

What is the role of neurosurgeons in the current management of intracranial aneurysm in France? An analysis of professional practices.

STUDY DESIGN: Retrospective observational survey-based study. INTRODUCTION: In France, intracranial aneurysm (IA) patients are managed by neurosurgeons and by interventional neuroradiologists. The growth of endovascular treatment led us to reflect on the role of neurosurgeons in the management of patients with IA. The present study aimed to highlight the current organization of IA management in France. METHOD: A 60-question survey was sent to the neurosurgeons in 34 hospitals managing IA patients. Thirty-three questions dealt with standards of care, follow-up procedures and the involvement of the specific specialist. RESULTS: Twenty-seven centers (79.4%) responded to the survey. A Vascular Multidisciplinary Discussion Team was organized, including both surgeons and neuroradiologists, in 92% of responding centers. There were department protocols in 66% of centers, a local registry in 33% and clinical trials in IA in 60%. Patients with unruptured IA were first seen by a neurosurgeon or by an interventional neuroradiologist, with different practices. For ruptured IA, the neurosurgeons were contacted first in 93% of cases, and were systematically involved in initial intensive care unit management. The patients were hospitalized in the neurosurgery department in 89% of the centers. The neurosurgeons took care of initial follow-up in 85% of the centers, and of lifetime follow-up in 36%. In most centers, radiological monitoring of IA was based on MRI angiography for patients who were embolized or under surveillance, and on CT angiography after microsurgery. CONCLUSION: Despite the growth of endovascular treatments, the present survey and the literature highlight a major role of neurosurgeons in treatment, follow-up and care coordination.

Ganglioglioma revealed by spontaneous intracerebral hematoma: A cohort study.

BACKGROUND: Gangliogliomas are rare tumors of the central nervous system. Intracerebral hemorrhage (ICH) is a frequent pathological event, rarely related to intracranial tumor. Here we report a cohort of 14 gangliogliomas, 3 of which were revealed by ICH. We also performed a systematic review of the literature on gangliogliomas revealed by ICH. PATIENTS AND METHODS: We retrospectively collected data for all gangliogliomas operated on in our department between January 2015 and December 2019: clinical history, radiological data and outcome, with a special focus on gangliogliomas revealed by spontaneous ICH. All cases had pathological validation. For the systematic review, relevant studies were identified by systematic search of the scientific literature in PubMed. RESULTS: Fifteen patients underwent surgery for ganglioglioma during the study period. Six cases were revealed by seizures, 3 by headache, 1 by hydrocephaly and 1 by developmental disorder. Three patients (21%) had hemorrhagic presentation. All patients were male, aged 30 to 48 years, diagnosed with atypical ICH without vascular abnormality on cerebral angiogram. Conservative management was first decided. Diagnosis of ganglioglioma was made within 3 months for 2 patients and 9 years later for 1, after surgical removal and histological analysis. All hemorrhagic gangliogliomas were BRAF wild type. The systematic review of the literature identified 8 other cases of ganglioglioma revealed by ICH. CONCLUSION: ICH may be a mode of revelation of ganglioglioma, and ganglioglioma is a possible etiology of atypical ICH in young patients. Long-term imaging follow-up is mandatory in patients with unexplained ICH.

Retreatment of previously treated intracranial aneurysm: Procedural complications and risk factors for complications.

OBJECTIVE: Intracranial aneurysm (IA) is a frequent vascular malformation that can be managed by endovascular treatment (EVT) or microsurgery. A previously treated IA can recanalize, which may require further treatment. The aim of our study was to evaluate procedural complications related to IA retreatment and their risk factors. METHODS: All patients retreated for IA between 2007 and 2017 in 4 hospitals were included. We retrospectively reviewed the frequency of procedural complications of IA retreatment, defined as death or≥1-point increase in modified Rankin score 24h after the procedure. We then screened for risk factors of procedural complications by comparing the characteristics of patients with and without complications. RESULTS: During the inclusion period, 4,997 IAs were treated in our 4 institutions. Of these, 237 (4.7%) were retreated. 29 (12.2%) had≥1 procedural complication. However, severe complications, defined as death or dependency at 1 month, occurred only in 3 patients (1.3%). The only risk factor for complications was microsurgical clipping as retreatment. CONCLUSIONS: Procedural complications during IA retreatment were frequent but, in most cases, retreatment did not lead to death or severe disability. The only risk factor for complications of IA retreatment was clipping as retreatment. However, the design of the study did not allow any conclusion to be drawn as to the optimal means of aneurysm retreatment, and further studies are needed.

Development and operation of the defence COVID-19 lab as a SARS-CoV-2 diagnostic screening capability for UK military personnel.

BACKGROUND: In the face of the COVID-19 pandemic, the Defence Science and Technology Laboratory (Dstl) and Defence Pathology combined to form the Defence Clinical Lab (DCL), an accredited (ISO/IEC 17025:2017) high-throughput SARS-CoV-2 PCR screening capability for military personnel. LABORATORY STRUCTURE AND RESOURCE: The DCL was modular in organisation, with laboratory modules and supporting functions combining to provide the accredited SARS-CoV-2 (envelope (E)-gene) PCR assay. The DCL was resourced by Dstl scientists and military clinicians and biomedical scientists. LABORATORY RESULTS: Over 12 months of operation, the DCL was open on 289 days and tested over 72 000 samples. Six hundred military SARS-CoV-2-positive results were reported with a median E-gene quantitation cycle (Cq) value of 30.44. The lowest Cq value for a positive result observed was 11.20. Only 64 samples (0.09%) were voided due to assay inhibition after processing started. CONCLUSIONS: Through a sustained effort and despite various operational issues, the collaboration between Dstl scientific expertise and Defence Pathology clinical expertise provided the UK military with an accredited high-throughput SARS-CoV-2 PCR test capability at the height of the COVID-19 pandemic. The DCL helped facilitate military training and operational deployments contributing to the maintenance of UK military capability. In offering a bespoke capability, including features such as testing samples in unit batches and oversight by military consultant microbiologists, the DCL provided additional benefits to the UK Ministry of Defence that were potentially not available from other SARS-CoV-2 PCR laboratories. The links between Dstl and Defence Pathology have also been strengthened, benefitting future research activities and operational responses.

Multimodal management of ruptured cerebral micro-arteriovenous malformations: A retrospective series of 19 cases and a review of the literature.

BACKGROUND: Micro-arteriovenous malformations (micro-AVMs) are defined as AVMs just visible on angiography with a nidus size between 0.5 and 1cm. Their principal manifestation is intracranial hemorrhage and their diagnosis and therapeutic management are still unclear. METHODS: The aim of our work was to show the clinical presentation, treatment and outcome of ruptured cerebral micro-AVMs in a retrospective cohort study of 19 patients and a systematic review of the literature. RESULTS: We obtained a total of 20 micro-AVMs in 19 patients. The mean age was 47.3 years. Clinical presentation was acute bleeding. The mean volume of hematoma was 12.9 mm3 (0 - 60.4), with topographic distribution as follows: 64% cortical with supratentorial bleeding, 26% deep, and 10% in the posterior fossa. Among the 20 micro-AVMs of the series, 11 (55%) had endovascular management, 6 (30%) had surgical treatment and 3 (15%) had GK radiosurgery alone. All of our patients have been cured at the end of the follow up without re-permeabilization. In our series, clinical outcome showed good recovery with a mean score of 4.6 on Glasgow Outcome Scale (GOS). In the literature, 88% of patients had a GOS of 4 or 5. DISCUSSION: Intracerebral hematoma (ICH) was the main clinical manifestation. In the case of negative initial angiographic assessment, patients must have supraselective angiographic exploration. In the case of conservative treatment of hematoma, endovascular obliteration and microsurgical exclusion seems to be reasonable therapeutic options, according to our observations.

Management of intracranial aneurysms in France: Place of microsurgery and demography of vascular neurosurgeons.

STUDY DESIGN: Observational retrospective survey-based study. INTRODUCTION: Intracranial aneurysms (IA) can be treated with microsurgery or by endovascular treatments (EVT). EVT have taken an increasingly important part in IA management; the ability of neurosurgical teams to perform such surgery as well as the quality of their training is being questioned. We therefore wanted to assess the proportion of IA treated by microsurgery in France, the demography and caseload of surgeons trained in vascular neurosurgery. METHODOLOGY: A 60-question survey was sent to the 34 French neurosurgical centers treating IA. Twenty-seven questions dealt with the demography of neurovascular surgeons and caseload. Descriptive data are reported here. RESULTS: Twenty-seven centers answered, giving us a response rate of 79.4%. A total of 209 neurosurgeons worked in these centers. Forty-six neurosurgeons were designated as referents in vascular neurosurgery, 47% of them were under 45 years old. Among the centers, 96.3% had at least one surgeon that was a referent in neurovascular surgery. A total of 88 surgeons performed IA surgery, but only 11 operated more than 20 IA per year. Two thousand four hundred and thirty seven unruptured IA were treated every year in these centers, 25% of which by microsurgery. A total of 2727 ruptured IA were treated in these centers, of which 15% were treated by microsurgery. The most common indications for microsurgical treatment of IA were: middle cerebral artery aneurysms, wide-neck intracranial aneurysms, and giant intracranial aneurysms, as well as aneurysms associated with a hematoma for the ruptured ones. CONCLUSION: Demography of vascular neurosurgeons remains favorable, with a referent neurosurgeon in most centers, who, in half of the cases, is a young practitioner. The percentage of microsurgery in the treatment of IA is low, especially for ruptured ones. The most frequently operated types of intracranial aneurysm correspond to good practice recommendations.

Functional outcome 1 year after aneurysmal subarachnoid hemorrhage due to ruptured intracranial aneurysm in elderly patients.

BACKGROUND: Population aging raises questions about extending treatment indications in elderly patients with aneurysmal subarachnoid hemorrhage (aSAH). We therefore assessed functional status 1 year after treatment. METHODS: This study involved 310 patients, aged over 70 years, with ruptured brain aneurysm, enrolled between 2008 and 2014 in a prospective multicentre trial (FASHE study: NCT00692744) but considered unsuitable for randomisation and therefore analysed in the observational arms of the study: endovascular occlusion (EV), microsurgical exclusion (MS) and conservative treatment. The aims were to assess independence, cognition, autonomy and quality of life (QOL) at 1 year post-treatment, using questionnaires (MMSE, ADLI, IADL, EORTC-QLQ-C30) filled in by independent nurses after discharge. RESULTS: The 310 patients received the following treatments: 208 underwent EV (67.1%), 54 MS (17.4%) and 48 were conservatively managed (15.5%). At 1 year, independence rates for patients admitted with good clinical status (WFNS I-III) were, according to the aneurysm exclusion procedure (EV, MS or conservative), 58.9%, 50% and 12.1% respectively. MMSE score was pathological in 26 of the 112 EV patients (23.2%), 10 of the 25 MS patients (40%) and 4 of the 9 patients treated conservatively (44%), without any statistically significant difference [Pearson's Chi2 test, F ratio=4.29; P=0.11]. Regarding QoL, overall score was similar between the EV and MS cohorts, but significantly lower with conservative treatment. CONCLUSION: Elderly patients in good clinical condition with aSAH should be treated regardless of associated comorbidities. Curative treatment (EV or MS) reduced mortality without increasing dependence, in comparison with conservative treatment.

[Candida albicans cerebral granuloma in an immunocompetent patient. A case report]. / Granulome cérébral àCandida albicans chez un patient immunocompétent. Cas clinique.

We report a case of temporal lobe granuloma caused by Candida albicans in an immunocompetent patient. This 54-year-old patient had experienced headaches and some memory disorders for two to three months before his admission to the neurosurgical department. Cerebral-computer tomography and magnetic resonance imaging showed a single right-temporal lesion with a large peritumoral edema. We operated on the patient via a temporal approach using neuronavigation and resected the lesion. The anatomopathological result and the cultures of the granuloma showed C. albicans species. The patient received antifungal therapy for three months. No predisposing factors or immunosuppression was found. After seven months, he presented an ischemic cerebrovascular accident of the brain stem and then chronic meningitis complicated by hydrocephalus. The patient's condition progressively deteriorated and he died 18 months later in an other department. C. albicans can be found even in the immunocompetent patient, but is seldom observed. Surgery can provide an accurate diagnosis and therapeutic management in the initial phase, completed by antifungal therapy.

[Bibliometric analysis of neurosurgery publications in France]. / État des lieux de l'activité de publications en neurochirurgie en France.

Bibliometrics are methods used to quantitatively analyze the scientific literature. The application of bibliometrics in neurosurgery is emerging and has not yet been studied in the French neurosurgical community. In France, the most used statistical method is named SIGAPS; the scores are based on the position of the author and the impact factor of the journal. The SIGAPS score, which can be calculated for a research team or an individual, impacts the public financial support of university hospitals in France. We analyzed retrospectively the publication productivity and the SIGAPS score of university neurosurgery departments in France for the period 2009-2016. This was supplemented by a list of current academic research protocols granted by the Minister of Health. The SIGAPS score is higher in large university hospitals even though all teams are dedicated to publishing more in the traditional neurosurgery journals (Neurosurgery, Journal of Neurosurgery, World Neurosurgery, J Neuro-oncology, Neuro oncology, Eur Spine J). Of note, the national Neurochirurgie journal (publishing in French and English) is progressively improving its impact factor (0.8). The most common themes are functional neurosurgery, neuro-oncology and spine. There are 14 on-going national multicenter research programs, 4 of them focused on the health economics of treatment innovations. These data provide the most accurate available snapshot of the scholarly efforts of all the French university neurosurgery departments. It is based on a national statistics method (SIGAPS). For future evaluation, it should be combined with internationally available parameters such as the h-index and m-quotient. Publication productivity has broad implications for the success of both academic departments and individual faculty members and their financial support.

Entrapment of the basilar artery within a clivus fracture: Case report and literature review.

A review of the literature revealed that basilar artery (BA) entrapment is a very rare (17 cases published) and severe pathological condition, which often leads to death. We report the case of a 72-year-old man who presented with a longitudinal clivus fracture associated with a basilar artery entrapment. This entrapment was responsible for a basilar artery dissection, which led to an ischemic stroke in the pons. The patient was managed with medical treatment, mainly to avoid a progression towards an ischemic stroke. It consisted of heparin therapy followed by antiplatelet therapy, which finally resulted in a successful outcome. In BA entrapment most of the patients who had a favorable outcome received antithrombotic therapy. This suggests that antithrombotic therapy might be useful in the first line treatment of post-traumatic BA entrapment.

FIVHeMA: Intraventricular fibrinolysis versus external ventricular drainage alone in aneurysmal subarachnoid hemorrhage: A randomized controlled trial.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) is a devastating form of stroke, which often causes acute hydrocephalus requiring the insertion of an external ventricular drain (EVD). A major complication of aneurysmal SAH is delayed cerebral ischemia (DCI). As DCI is linked to the presence of blood within the subarachnoid space, it has been hypothesized that removing this blood may decrease the risk of DCI. This could be achieved by injecting a fibrinolytic agent through the EVD, a strategy called intraventricular fibrinolysis (IVF). Here, we propose to conduct a phase III trial to directly evaluate the impact of IVF after aneurysmal SAH. MATERIALS AND METHODS: We will perform an open-label randomized controlled trial comparing the standard of care, i.e. EVD alone, to the experimental treatment, i.e. IVF. We plan to include 440 patients to be able to show a 10% increase in the rate of good functional outcomes in the EVD+IVF group compared to the EVD alone group (α=0.05 and ß=0.8). To obtain such sample, a multicenter trial is required, and to date 17 research sites in France have agreed to participate. PERSPECTIVE: FIVHeMA would be the first phase III trial evaluating the relevance of IVF in aneurysmal SAH. If IVF is shown to be beneficial, then a new therapeutic tool will be available to improve the outcomes of aneurysmal SAH patients.

Hypofractionated stereotactic radiotherapy for challenging brain metastases using 36 Gy in six fractions.

PURPOSE: Stereotactic radiosurgery and hypofractionated stereotactic radiotherapy are standard treatments for brain metastases when they are small in size (at the most 3cm in diameter) and limited in number, in patients with controlled extracerebral disease and a good performance status. Large inoperable brain metastases usually undergo hypofractionated stereotactic radiotherapy while haemorrhagic brain metastases have often been contraindicated for both stereotactic radiosurgery or hypofractionated stereotactic radiotherapy. The objective of this retrospective study was to assess a six 6Gy-fractions hypofractionated stereotactic radiotherapy scheme in use at our institution for haemorrhagic brain metastases, large brain metastases (size greater than 15cm3) or brain metastases located next to critical structures. MATERIAL AND METHODS: Patients with brain metastases treated with the 6×6Gy scheme since 2012 to 2016 were included. Haemorrhagic brain metastases were defined by usual criteria on CT scan and MRI. Efficacy, acute and late toxicity were evaluated. RESULTS: Sixty-two patients presenting 92 brain metastases were included (32 haemorrhagic brain metastases). Median follow up was 10.1 months. One-year local control rate for haemorrhagic brain metastases, large brain metastases, or brain metastases next to critical structures were 90.7%, 73% and 86.7% respectively. Corresponding overall survival rates were 61.2%, 32% and 37.8%, respectively. Haemorrhagic complications occurred in 5.3% of patients (N=5), including two cases of brain metastases with pretreatment haemorrhagic signal. Tolerance was good with only one grade 3 acute toxicity. CONCLUSION: The 6×6Gy hypofractionated stereotactic radiotherapy scheme seems to yield quite good results in patients with haemorrhagic brain metastases, which must be confirmed in a prospective way.

[Current management of brain metastases]. / Traitement actuel des métastases cérébrales.

INTRODUCTION: Cerebral metastases occur in 15 to 20% of cancers and their incidence is increasing. The majority occur at an advanced stage of the disease, but metastasis may be the inaugural sign of cancer. The aim of treatments, which are often palliative, is to preserve the neurological status of the patient with the best quality of life. STATE OF ART: Corticosteroids are widely used for symptomatic palliation, requiring close monitoring and regular dose adaptation. Antiepileptic drugs should be given only for patients who have had a seizure. In case of multiple cerebral metastases occurring at an advanced stage of the disease, whole brain radiation is the most effective therapy for rapid symptom control. However, radiotherapy moderately improves overall survival, which often depends on the progression of disseminated systemic disease. On the contrary, surgery is indicated in case of a solitary metastasis, particularly when the patient is young (less than 65 years), with good general status (Karnofsky greater than 70), and when the systemic disease is under control. Radiosurgery offers an attractive alternative for these patients with good prognostic factors and a small number of cerebral metastases (< or = 4). PERSPECTIVES: Chemotherapy, considered in the past as not effective, is taking on a more important place in patients with multiple nonthreatening metastases from chemosensitive cancers (breast, testes...). Radiosurgery and whole brain radiotherapy are complementary techniques. Their respective role in the management of multiple metastases (< 4) remains to be further investigated. CONCLUSIONS: Therapeutic options are increasingly effective to improve the functional prognosis of patients with cerebral metastases. Ideally, a multidisciplinary assessment offers the best choice of therapeutic modalities.

How to perform microscopic/endoscopic resection of large petrous apex lesions.

The endoscope and microscope can be used conjointly in certain sites, such as middle ear cholesteatoma or for resection of cerebellopontine angle tumours. Petrous apex tumours are classically accessed via a lateral otological approach, or, for the most anterior tumours, via an endonasal endoscopic approach. Surgical access via a lateral incision is limited inferiorly by the superior bulb of the internal jugular vein, medially by the labyrinth, facial nerve and internal auditory canal, superiorly by the dura mater, and laterally by the internal carotid artery. Via an anterior endonasal approach, the corridor formed by the internal carotid artery and the paraclival dura limits access to the posterior part of the petrous apex, restricting this approach to certain cholesterol granulomas or small cholesteatomas. None of these approaches, on its own, is sufficient in the case of an extensive petrous apex lesion. The objective of this technical note is to describe the combined microscopic/endoscopic approach comprising sequential use of the microscope and the endoscope via a lateral approach for the management of large petrous apex lesions.