Comparison of scales for the evaluation of aneurysmal subarachnoid haemorrhage: a retrospective cohort study.

BACKGROUND/OBJECTIVES: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening event with major complications. Delayed cerebral infarct (DCI) occurs most frequently 7 days after aSAH and can last for a prolonged period. To determine the most predictive radiological scales in grading subarachnoid or ventricular haemorrhage or both for functional outcome at 3 months in a large aSAH population, we conducted a single-centre retrospective study. METHODS: A 3-year single-centre retrospective cohort study of 230 patients hospitalised for aSAH was analysed. Initial computed tomography (CT) scans in patients hospitalised for aSAH were blindly assessed using eight grading systems: the Fisher grade, modified Fisher grade, Barrow Neurological Institute scale, Hijdra scale, Intraventricular Haemorrhage (IVH) score, Graeb score and LeRoux score. RESULTS: Of 200 patients with aSAH who survived to day 7 and were included for DCI analysis, 39% of cases were complicated with DCI. The Hijdra scale was the best predictor for DCI, with a receiver operating characteristic area under the curve (ROCAUC) of 0.80 (95% confidence interval (CI), 0.74-0.85). The IVH score was the most effective grading system for predicting acute hydrocephalus, with a ROCAUC of 0.85 (95% CI, 0.79-0.89). In multivariate analysis, the Hijdra scale was the best predictor of the occurrence of DCI (hazard ratio, 1.18; 95% CI, 1.10-1.25). CONCLUSIONS: Although these results have yet to be prospectively confirmed, our findings suggest that the Hijdra scale may be a good predictor of DCI and could be useful in daily clinical practice. CLINICAL RELEVANCE STATEMENT: Better assessment of subarachnoid haemorrhage patients would allow for better prognostication and management of expectations, as well as referral for appropriate services and helping to appropriate use limited critical care resources. KEY POINTS: Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction. Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct. The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.

Outcome of non-functioning ACTH pituitary tumors: silent does not mean indolent.

INTRODUCTION: Silent corticotroph tumors (siACTH) represent a rare entity of pituitary tumors (PT), usually more aggressive than other PT. Few predictor factors of recurrence in the post-operative period have been proposed until now. This study aimed (1) to evaluate the clinical outcome of siACTH after surgery according to a five-tiered clinicopathological classification (2) to compare siACTH characteristics to ACTH-secreting macroadenomas (macroCD), and silent gonadotropinomas (siLH/FSH). PATIENTS AND METHODS: Between 2008 and 2022, 29 siACTH out of 865 PT cases operated in one tertiary center were included. Clinical, paraclinical, histological, and surgical data were collected and compared to 25 macroCD and 143 siLH/FSH cases, respectively. The tumor grading was established according to both invasion (no = 1; yes = 2) and proliferation (no = a; yes = b). Progression-free survival was estimated using Kaplan-Meier method and log-rank test. RESULTS: We identified 15 (51.7%) grade 1a, 11 (37.9%) grade 2a and 3 (10.3%) grade 2b siACTH with a trend for a 7-fold-time higher risk of progression/recurrence in grade 2b as compared to 1a (p = 0.06). The repartition of tumor grades was similar between the three subgroups, however a 5.7-fold-higher risk of progression was observed in grade 1a siACTH than in grade 1a siLH/FSH (p = 0.02). Compared to siLH/FSH, higher ACTH levels may help to preoperatively identify siACTH. CONCLUSION: The five-tiered clinicopathological classification contribute to predict the risk of recurrence of operated siACTH tumors. Noteworthy, non-invasive and non-proliferative siACTH exhibit a less favorable outcomes than their siLH/FSH counterparts, which should prompt for a personalized follow up.

Fully endoscopic endonasal approach for the treatment of intrasellar arachnoid cysts.

PURPOSE: To report our experience of endoscopic endonasal obliteration of symptomatic sellar arachnoid cyst (SAC). METHODS: From 2002 to 2019, we retrospectively reported the data of 17 cases of SAC operated in Timone University Hospital, Marseille, France. Preoperative clinical findings were collected including main symptoms, visual function and endocrinological assessment. Surgical procedure was homogeneous and consisted in endonasal fully endoscopic surgical obliteration of the cyst cavity with fat graft. Post-operative outcomes, complication and follow-up was reported. RESULTS: Visual disorders and/or headaches were the main symptoms. Our technique provided improvement for 83.3% of the patients suffering from visual disturbance and for 87.5% of those suffering from headaches. We reported 2 cases of cerebrospinal fluid (CSF) leakage (11.8%), but no meningitis. One case of definitive diabetes insipidus occurred and one case of postoperative syndrome of inappropriate antidiuretic hormone secretion was temporary. There was one case of recurrence reported. The mean follow-up was 39 months. CONCLUSION: Patients with symptomatic SAC can be treated successfully by endoscopic endonasal obliteration of the cyst. This simple technique offers true benefits for the patients without craniotomy, but the complication rate remains high especially with the risk of CSF leakage. Special attention to skull base opening and closing could reduce this risk.

Long-term surgical oncological and functional outcome of large petroclival and cerebellopontine angle epidermoid cysts: a multicenter study.

Cranial nerve (CN) disorders are the foremost symptoms in cerebellopontine angle (CPA) and petroclival area (PCA) epidermoid cysts (EC).The aim of this work was to  assess the long-term surgical results on CN function and tumor control in these patients. We performed a retrospective cohort study about 56 consecutive patients operated on for a CPA or PCA EC between January 2001 and July 2019 in six participating French cranial base referral centers. Sixteen patients (29%) presented a PCA EC and 40 a CPA EC (71%). The median clinical and radiological follow-up was 46 months (range 0-409). Preoperative CN disorders were present in 84% of patients (n = 47), 72% of them experienced CN deficits improvement at the last follow-up consultation (n = 34): 60% of cochlear and vestibular deficits (n = 9/15 in both groups), 67% of trigeminal neuralgia (n = 10/15), 53% of trigeminal hypoesthesia (n = 8/15), 44% of lower cranial nerve disorders (n = 4/9), 38% of facial nerve deficits (n = 5/8) and 43% of oculomotor deficits (n = 3/7) improved or were cured after surgery. New postoperative CN deficits occurred in 48% of patients (n = 27). Most of them resolved at the last follow-up, except for cochlear deficits which improved in only 14% of cases (n = 1/7). Twenty-six patients (46%) showed evidence of tumor progression after a median duration of 63 months (range 7-210). The extent of resection, tumor location, and tumor size was not associated with the occurrence of new postoperative CN deficit or tumor progression. A functional nerve-sparing resection of posterior fossa EC is an effective strategy to optimize the results on preexisting CN deficits and reduce the risk of permanent de novo deficits.

Crossed brainstem syndrome revealing bleeding brainstem cavernous malformation: an illustrative case.

BACKGROUND: Since the nineteenth century, a great variety of crossed brainstem syndromes (CBS) have been described in the medical literature. A CBS typically combines ipsilateral cranial nerves deficits to contralateral long tracts involvement such as hemiparesis or hemianesthesia. Classical CBS seem in fact not to be so clear-cut entities with up to 20% of patients showing different or unnamed combinations of crossed symptoms. In terms of etiologies, acute brainstem infarction predominates but CBS secondary to hemorrhage, neoplasm, abscess, and demyelination have been described. The aim of this study was to assess the proportion of CBS caused by a bleeding episode arising from a brainstem cavernous malformation (BCM) reported in the literature. CASE PRESENTATION: We present the case of a typical Foville syndrome in a 65-year-old man that was caused by a pontine BCM with extralesional bleeding. Following the first bleeding episode, a conservative management was decided but the patient had eventually to be operated on soon after the second bleeding event. DISCUSSION: A literature review was conducted focusing on the five most common CBS (Benedikt, Weber, Foville, Millard-Gubler, Wallenberg) on Medline database from inception to 2020. According to the literature, hemorrhagic BCM account for approximately 7 % of CBS. Microsurgical excision may be indicated after the second bleeding episode but needs to be carefully weighted up against the risks of the surgical procedure and openly discussed with the patient. CONCLUSIONS: In the setting of a CBS, neuroimaging work-up may not infrequently reveal a BCM requiring complex multidisciplinary team management including neurosurgical advice.

Chiasmapexy for secondary empty sella syndrome: diagnostic and therapeutic considerations.

PURPOSE: Secondary empty sella syndrome (SESS) following pituitary surgery remains a diagnostic and therapeutic challenge. The aim of this study was to specify the diagnostic criteria, surgical indications and results of chiasmapexy in the SESS. METHODS: Three cases from two experienced neurosurgical centers were collected and the available literature was reviewed. RESULTS: The 3 patients were operated for a giant non-functioning pituitary adenoma, a cystic macroprolactinoma, and an arachnoid cyst respectively. Postoperative visual outcome was initially improved, and then worsened progressively. At the time of SESS diagnosis, visual field defect was severe in all cases with optic nerve (ON) atrophy in 2 cases. Patients were operated via an endoscopic endonasal extradural approach. One patient was re-operated because of early fat reabsorption. Visual outcome improved in 1 case and stabilized in 2 cases. Statistical analyses performed on 24 cases from the literature review highlighted that patient age and severity of the preoperative visual defect were respectively significant and nearly significant prognostic factors for visual outcome, unlike the surgical technique. CONCLUSION: T2-weighted or CISS/FIESTA sequence MRI is mandatory to visualize adhesions, ON kinking and neurovascular conflict. TS approach is the most commonly used approach. The literature review could not conclude on the need for an intra or extradural approach suggesting case by case adapted strategy. Intrasellar packing with non-absorbable material such as bone should be considered. Severity of the visual loss clearly decreases the visual outcome suggesting early chiasmapexy. In case of severe and long standing symptoms before surgery, benefits and surgical risks should be carefully balanced.

Characterization of the ability of a, second-generation SST-DA chimeric molecule, TBR-065, to suppress GH secretion from human GH-secreting adenoma cells.

CONTEXT: Somatostatin (SST) and dopamine (DA) inhibit growth hormone (GH) secretion and proliferation of GH-secreting pituitary adenomas (GHomas) through binding to SSTR2 and D2R receptors. Chimeric SST-DA compounds (Dopastatins) display increased potency in inhibiting GH secretion, as compared with individual SST or DA analogs (alone or combined). OBJECTIVE: To assess the efficacy of a second-generation dopastatin, TBR-065, in suppressing GH secretion from human GH- and GH/prolactin(PRL)-omas. DESIGN: We compared the ability of TBR-065 to inhibit GH secretion from primary cultures of human GH- or GH/PRLoma cells to that of the first generation dopastatin, TBR-760 (formerly BIM-23A760), octreotide (OCT) and cabergoline (CAB), the later either alone or combined. We investigated whether there was any impact of BIM-133, the metabolite of TBR-065, on the ability of TBR-065 to inhibit GH in these cultures. METHODS: 17 GH- and GH/PRLomas were included in this study. Inhibition of GH secretion by TBR-065, TBR-760, OCT and CAB (0.1 pM to 0.1 µM) was assessed over a period of 8 h. RESULTS: All tumors expressed SSTR2 and D2R mRNAs. GH suppression was higher with TBR-065 as compared with TBR-760 (Emax = 57 ± 5.6% vs. 41.1 ± 12.5%, respectively, p < 0.001) or with OCT + CAB (Emax = 56.8 ± 7.2% vs. 44.4 ± 9.4%, p < 0.001). BIM-133 did not have any impact on the activity of TBR-065. CONCLUSION: TBR-065 has significantly improved efficacy in suppressing GH secretion as compared to current available therapies and may represent a new promising option for the treatment of acromegaly.

Ipsilateral vs controlateral approach in tuberculum sellae meningiomas surgery: a retrospective comparative study.

Most of tuberculum sellae meningiomas (TSM) show asymmetric growth. They are usually resected through ipsilateral approaches. The access of the inferior-medial side of the ipsilateral optic nerve might be challenging, which result in increased manipulation of the compromised optic nerve. The contralateral approach has been described to avoid these technical difficulties. Assessing the long-term visual and olfactory outcome, as well as recurrence rate in patients operated for TSM through ipsilateral or contralateral approaches. Single center retrospective cohort study about 94 patients operated on between March 2000 and April 2018. Seventy percent of the preoperative visual acuity loss totally resolved (44%) or showed varying degrees of improvement (26%) after surgery. Seventy-two percent of the preoperative visual field defects evolved favorably (44% recovery, 28% improvement). Eight patients showed aggravated visual disturbances (9%). A contralateral approach seemed to be predictive of visual field defects improvement after surgery (OR = 0.4), with borderline significant results (p = .08). There was a higher rate of postoperative olfactory nerve impairment after a contralateral approach (37% vs 17%, p = .03). Total removal of the tumor fragment entering the optic canal was accomplished in 96% in the contralateral vs 75% in the ipsilateral group (p = .04). The 2-, 5-, and 7-year tumor progression-free survival were 100% in the Simpson grade 2 group, and 85% (n = 17), 74% (n = 11), and 67% (n = 5) in the Simpson grade 4 group, respectively (p = .00). Resection of tuberculum sellae meningiomas through a contralateral approach seems to provide better visual outcome and tumor control at the cost of increased olfactory nerve disorders.

Somatotroph Tumors and the Epigenetic Status of the GNAS Locus.

Forty percent of somatotroph tumors harbor recurrent activating GNAS mutations, historically called the gsp oncogene. In gsp-negative somatotroph tumors, GNAS expression itself is highly variable; those with GNAS overexpression most resemble phenotypically those carrying the gsp oncogene. GNAS is monoallelically expressed in the normal pituitary due to methylation-based imprinting. We hypothesize that changes in GNAS imprinting of gsp-negative tumors affect GNAS expression levels and tumorigenesis. We characterized the GNAS locus in two independent somatotroph tumor cohorts: one of 23 tumors previously published (PMID: 31883967) and classified by pan-genomic analysis, and a second with 82 tumors. Multi-omics analysis of the first cohort identified a significant difference between gsp-negative and gsp-positive tumors in the methylation index at the known differentially methylated region (DMR) of the GNAS A/B transcript promoter, which was confirmed in the larger series of 82 tumors. GNAS allelic expression was analyzed using a polymorphic Fok1 cleavage site in 32 heterozygous gsp-negative tumors. GNAS expression was significantly reduced in the 14 tumors with relaxed GNAS imprinting and biallelic expression, compared to 18 tumors with monoallelic expression. Tumors with relaxed GNAS imprinting showed significantly lower SSTR2 and AIP expression levels. Altered A/B DMR methylation was found exclusively in gsp-negative somatotroph tumors. 43% of gsp-negative tumors showed GNAS imprinting relaxation, which correlated with lower GNAS, SSTR2 and AIP expression, indicating lower sensitivity to somatostatin analogues and potentially aggressive behavior.

Parasellar Meningiomas.

Parasellar spaces remain particularly singular, comprising the most important neurovascular structures such as the internal carotid artery and optic, oculomotor, and trigeminal nerves. Meningiomas are one of the most frequent tumors arising from parasellar spaces. In this location, meningiomas remain mostly benign tumors with WHO grade I and a meningothelial subtype. Progestin intake should be investigated and leads mostly to conservative strategies. In the case of benign nonsymptomatic tumors, observation should be proposed. Tumor growth will lead to the proposition of surgery or radiosurgery. In the case of an uncertain diagnosis and an aggressive pattern, a precise diagnosis is required. For cavernous sinus and Meckel's cave lesions, complete removal is rarely considered, leading to the proposition of an endoscopic endonasal or transcranial biopsy. Optic nerve decompression could also be proposed via these approaches. A case-by-case discussion about the best approach is recommended. A transcranial approach remains necessary for tumor removal in most cases. Vascular injury could lead to severe complications. Cerebrospinal fluid leakage, meningitis, venous sacrifice, visual impairment, and cranial nerve palsies are more frequent complications. Pituitary dysfunctions are rare in preoperative assessment and in postoperative follow-up but should be assessed in the case of meningiomas located close to the pituitary axis. Long-term follow-up is required given the frequent incomplete tumor removal and the risk of delayed recurrence. Radiosurgery is relevant for small and well-limited meningiomas or intra-cavernous sinus postoperative residue, whereas radiation therapy and proton beam therapy are indicated for large, extended, nonoperable meningiomas. The place of the peptide receptor radionuclide therapyneeds to be defined. Targeted therapy should be considered in rare, recurrent, and aggressive parasellar meningiomas.

Correction to: Molecular revolution in the diagnosis of microbial brain abscesses.

An erratum to this paper has been published: https://doi.org/10.1007/s10096-020-04047-8.

Surgical indications for pituitary tumors during pregnancy: a literature review.

PURPOSE: Surgical indications for pituitary tumors during pregnancy are rare, and are derived from a balance between expected benefits, particularly for maternal benefits, and anesthetic/surgical risks. METHODS: A literature review was performed to define the optimal surgical indications for pituitary adenomas (PA) and other pituitary tumors during pregnancy. RESULTS: Main benefits are expected in case of critical visual impairment and/or life-threatening endocrine disturbances. Multidisciplinary patient management is systematically required although nonobstetric surgery presents a reasonable risk during pregnancy. The risks of congenital malformation during the first trimester and those of premature birth during the third trimester make the second trimester the optimal period for surgery. In prolactin-secreting, nonsecreting, GH- and TSH-secreting PAs, transsphenoidal surgery (TS) is recommended in cases involving severe visual impairment, characterized by severe visual field deficit, visual acuity impairment, and abnormal optical coherence tomography findings, and when no other medical alternatives are possible and/or sufficient. Uncontrolled and severe Cushing's disease (CD) during pregnancy increases both maternal and fetal morbimortality, thus justifying TS or sometimes dopamine agonist therapy as a safer alternative. Finally, metyrapone, ketoconazole, or bilateral adrenalectomy could be recommended in certain cases after the failure of medical therapies and/or TS. Surgery is also required for suprasellar meningiomas, craniopharyngiomas, and pituitary cysts in the case of severe visual deficit. CONCLUSION: Surgical indications for pituitary tumors are rare during pregnancy; therefore, surgery should be avoided when possible. Further, the second trimester should be considered as the optimal surgical period. Severe visual disturbance and uncontrolled CD are the main surgical indications during pregnancy.

Surgical management of craniopharyngiomas in adult patients: a systematic review and consensus statement on behalf of the EANS skull base section.

BACKGROUND AND OBJECTIVE: Craniopharyngiomas are locally aggressive neuroepithelial tumors infiltrating nearby critical neurovascular structures. The majority of published surgical series deal with childhood-onset craniopharyngiomas, while the optimal surgical management for adult-onset tumors remains unclear. The aim of this paper is to summarize the main principles defining the surgical strategy for the management of craniopharyngiomas in adult patients through an extensive systematic literature review in order to formulate a series of recommendations. MATERIAL AND METHODS: The MEDLINE database was systematically reviewed (January 1970-February 2019) to identify pertinent articles dealing with the surgical management of adult-onset craniopharyngiomas. A summary of literature evidence was proposed after discussion within the EANS skull base section. RESULTS: The EANS task force formulated 13 recommendations and 4 suggestions. Treatment of these patients should be performed in tertiary referral centers. The endonasal approach is presently recommended for midline craniopharyngiomas because of the improved GTR and superior endocrinological and visual outcomes. The rate of CSF leak has strongly diminished with the use of the multilayer reconstruction technique. Transcranial approaches are recommended for tumors presenting lateral extensions or purely intraventricular. Independent of the technique, a maximal but hypothalamic-sparing resection should be performed to limit the occurrence of postoperative hypothalamic syndromes and metabolic complications. Similar principles should also be applied for tumor recurrences. Radiotherapy or intracystic agents are alternative treatments when no further surgery is possible. A multidisciplinary long-term follow-up is necessary.

Correction to: Neuro-radiological characteristics of adult diffuse grade II and III insular gliomas classified according to WHO 2016.

In the initial, online publication, the authors' given names were captured as family names and vice versa. The names are correctly shown here. The original article has been corrected.

Neuro-radiological characteristics of adult diffuse grade II and III insular gliomas classified according to WHO 2016.

INTRODUCTION: The phenotypic heterogeneity of diffuse gliomas is still inconsistently explained by known molecular abnormalities. Here, we report the molecular and radiological features of diffuse grade WHO II and III gliomas involving the insula and its potential impact on prognosis. METHODS: Clinical, pathological, molecular and neuro-radiological features of 43 consecutive patients who underwent a surgical resection between 2006 and 2013 for a grade II and III gliomas involving the insula was retrospectively analyzed. RESULTS: Median age was 44.4 years. Eight patients had oligodendrogliomas, IDH mutant (IDHmut) and 1p/19q-codeleted (6 grade II, 2 grade III). Twenty-eight patients had diffuse astrocytomas, IDHmut (22 grade II and 6 grade III) and seven patients had grade II diffuse astrocytomas, IDHwt (A-IDHwt). Vimentin staining was exclusively recorded in tumor cells from A-IDHwt (p = 0.001). Mean cerebral blood volume (CBV) (p = 0.018), maximal value of CBV (p = 0.017) and ratio of the corrected CBV (p = 0.022) were lower for A-IDHwt. Volumetric segmentation of ADC allowed the identification of the tumor cores, which were smaller in A-IDHwt (p < 0.001). The tumor occurrences of A-IDHwt were exclusively located into the temporo-insular region. Median progression-free survival (PFS) and overall survival (OS) were 50.9 months (95% CI: 26.7-75.0) and 80.9 months (60.1-101.6). By multivariate analysis, A-IDHwt (p = 0.009; p = 0.019), 7p gain and 10q loss (p = 0.009; p = 0.016) and vimentin positive staining (p = 0.011; p = 0.029) were associated with poor PFS and OS respectively. CONCLUSIONS: Insular low-grade A-IDHwt presented with poor prognosis despite a smaller tumor core and no evidence of increased perfusion on MR imaging.

Interfascial approach for pterional craniotomy: technique and adjustments to prevent cosmetic complications.

BACKGROUND: Interfascial dissection for pterional craniotomy is one of the main techniques to expose the pterional region. METHOD: A step-by-step optimized method of interfascial dissection to avoid three main esthetic complications of the pterional approach-upper facial nerve palsy, temporal muscle atrophy, and retro-orbital depression. A video of the interfascial dissection and three artistic drawings are provided in support of this technique. CONCLUSION: A safe method of interfascial dissection, respecting anatomy, and avoiding cosmetic complications has been proposed.

Robot-assisted multi-level anterior lumbar interbody fusion: an anatomical study.

BACKGROUND: Minimally invasive surgical approaches still provide limited exposure. Access to the L2-L5 intervertebral discs during a single procedure is challenging and often requires repositioning of the patient and adopting an alternative approach. OBJECTIVES: Investigate the windows to the L2-L5 intervertebral discs to assess the dimensions of the interbody implants suitable for the procedure and evaluate the feasibility of multi-level lumbar intervertebral disc surgery in robot-assisted surgery (RAS) METHODS: Sixteen fresh-frozen cadaveric specimens underwent a retroperitoneal approach to access the L2-L5 intervertebral discs. The L2-L3 to L4-L5 windows were defined as the distance between the left lateral border of the aorta (or nearest common iliac vessel) and the medial border of the psoas, measured in a static state and after gentle medial retraction of the vascular structures. Two living porcine specimens and one cadaveric specimen underwent da Vinci robot-assisted transperitoneal approach to expose the L2-L3 to L4-L5 intervertebral discs and perform multi-level discectomy and interbody implant placement. RESULTS: The L2-L3 to L4-L5 intervertebral disc windows significantly increased from a static to a retracted state (p < 0.05). The mean L2-L3, L3-L4, and L4-L5 windows measured respectively 20.1, 21.6, and 19.6 mm in the static state, and 27.2, 30.9, and 30.3 mm after gentle vascular retraction. The intervertebral windows from L2-L3 to L4-L5 were successfully exposed through an anterior transperitoneal approach with the da Vinci robot on the cadaveric and living porcine specimens, and interbody implants were inserted. CONCLUSION: RAS appears to be feasible for a mini-invasive multi-level lumbar intervertebral disc surgery. The RAS procedure, longer and more expensive than conventional MIS approaches, should be reserved for elective patients.

Evidence of Archaeal Methanogens in Brain Abscess.

Background: Methanogens are antibiotic-resistant anaerobic archaea that escape routine detection in clinical microbiology. We hypothesized that methanogens are part of the anaerobic community that cause brain abscess. Methods: Methanogens were investigated in 1 index sample using specific polymerase chain reaction (PCR) sequencing and culture. The pathogenesis of a methanogen isolate was assessed in a mouse model. Archaea-specific quantitative (q) PCR and metagenomics were used to detect specific archaeal sequences in brain abscess samples and controls. Results: In 1 index sample, routine culture found Porphyromonas endodontalis and Streptococcus intermedius, and specific culture found Methanobrevibacter oralis susceptible to metronidazole and fusidic acid. Archaea-targeted PCR sequencing and metagenomics confirmed M. oralis along with 14 bacteria, including S. intermedius. Archaea-specific qPCR yielded archaea in 8/18 brain abscess specimens and 1/27 controls (P < .003), and metagenomics yielded archaea, mostly methanogens, in 28/32 brain abscess samples, and no archaea in 71 negative controls (P < 10-6). Infection of mice brains yielded no mortality in 14 controls and death in 17/22 M. oralis-inoculated mice (P < 10-6), 32/95 S. intermedius-inoculated mice (P < 10-6), and 75/104 mice inoculated with M. oralis mixed with S. intermedius (P < 10-6) 7 days post-inoculation. Conclusion: Methanogens belong to the anaerobic community responsible for brain abscess, and M. oralis may participate in the pathogenicity of this deadly infection. In mice, a synergy of M. oralis and S. intermedius was observed. Antibiotic treatment of brain abscess should contain anti-archaeal compounds such as imidazole derivatives in most cases.

Early matrix metalloproteinase-9 concentration in the first 48 h after aneurysmal subarachnoid haemorrhage predicts delayed cerebral ischaemia: An observational study.

BACKGROUND: Delayed cerebral ischaemia from vasospasm is an important cause of complications and death after aneurysmal subarachnoid haemorrhage. There is currently no established biomarker for identifying patients at high risk of delayed cerebral ischaemia. OBJECTIVE: Considering the important role of inflammation in the pathogenesis of delayed cerebral ischaemia, we investigated whether matrix metalloproteinase-9 (MMP-9) may be an efficient biomarker for predicting elayed cerebral ischaemia after subarachnoid haemorrhage. DESIGN: Single-centre prospective observational study. SETTING: Neuroscience Critical Care Unit of a teaching hospital. PARTICIPANTS: Thirty consecutive patients with severe subarachnoid haemorrhage requiring external ventricular drainage were enrolled during 2013 and 2014. INTERVENTIONS: Blood and cerebrospinal fluid (CSF) were sampled within the first 24 h and between 48 and 72 h after admission. We evaluated the activity and concentrations of MMP-9 and endothelin-1 with zymography and ELISA. Patients were allocated to groups with delayed cerebral ischaemia (n = 16) or without delayed cerebral ischaemia (n = 14). RESULTS: Within 24 h, median [interquartile range] MMP-9 concentrations in CSF were significantly higher in patients with delayed cerebral ischaemia (47 [21 to 102] ng ml) than in those without delayed cerebral ischaemia (4 [2 to 13] ng ml, P = 0.001). CSF MMP-9 activity and endothelin-1 concentrations were correlated (r = 0.6, P = 0.02). The areas under the receiver operating characteristic curves were 0.73 (95% confidence interval [0.53 to 0.87]) and 0.91 (95% confidence interval [0.75 to 0.98]) for MMP-9 concentrations in plasma and CSF, respectively, at 24 h to predict delayed cerebral ischaemia CSF MMP-9 concentrations more than 14.3 ng ml at 24 h predicted the occurrence of delayed cerebral ischaemia with a sensitivity and specificity of 88 and 86%, respectively. After multivariate logistic analysis, only CSF MMP-9 concentrations at 24 h predicted the occurrence of delayed cerebral ischaemia (P = 0.01). CONCLUSION: MMP-9 concentrations in both plasma and CSF, measured within 48 h after subarachnoid haemorrhage, were highly predictive of the occurrence of delayed cerebral ischaemia within the first 2 weeks. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02397759.