Severe Intracranial Infection Research Articles

An active & passive dual-targeting platform for the precise treatment, process monitoring and effective protection of central nervous system infection

Precise antibacterial activity and effective inflammatory response reduction are critical for successful treatment of Intracranial infection after craniocerebral surgery, which remains an unmet clinical challenge. Herein, an intracranial drug delivery liposome (AFAA-lipo) that possesses dual active&passive targeting capability, direct antibacterial ability, favorable inflammation regulation, and excellent biocompatibility is developed as an antibiotics-free and hardly bacterial-resistance-induced platform for the management of intracranial infection. The surface-anchored specific peptide sequence HRERMS (the oligopeptide designed sourced from β-amyloid precursor protein) makes AFAA-lipo actively penetrate the blood–brain barrier and then perforated and lysed under the stimulation of α-toxin secreted by methicillin-resistant Staphylococcus aureus (MRSA, a severe and widespread intracranial infection type) in the infected site. Our results demonstrate that the AFAA-lipo can eliminate bacteria and biofilms, and reduce inflammatory response through mitochondrial function protection, DNA preservation from damage, TNFR1/NF-κB signaling pathway inhibition, and promotion of microglial polarization towards the anti-inflammatory subtype, ultimately improving post-infection prognosis and survival rate. More interestingly, the pre-intake of AFAA-lipo is capable to reduce MRSA infection risk and alleviate inflammatory response. Furthermore, the near-infrared (NIR) II region imaging fluorescence signal intensity variations of AFAA-lipo is proved the validation to monitor the course of the disease.

Study of Bitespiramycin Distribution in Rats and Cerebrospinal Fluid of Patients by a Sensitive LC-MS/MS Method with Rapid Sample Preparation.

Bitespiramycin, has been shown to have a therapeutic effect against respiratory tract inflammation, including a potential effect against COVID-19. A current clinical trial in China showed that bitespiramycin was an effective treatment for severe pneumonia and intracranial infection. However, there is lack of an analytical method to elucidate the distribution of bitespiramycin. In this study, a highly sensitive, rapid and reliable UPLC-MS/MS method was developed to comprehensively characterize the bitespiramycin distribution in various bio-samples, which is significantly improved upon the published work. A rapid sample preparation method was developed by using n-butanol as the solvent to extract bitespiramycin from different bio-samples. The extract was then directly analyzed by UPLC-MS/MS coupled with an alkaline-resistant column after centrifugation which avoids the time-consuming concentration process under nitrogen and redissolution. The method was employed to accurately quantify bitespiramycin and its metabolites in rat plasma, tissues, and human cerebrospinal fluid. Notably, the presence of bitespiramycin and its metabolites was identified for the first time in various rat organs including brain, testis, bladder and prostate as well as in human cerebrospinal fluid. This newly developed approach shows great promise for drug distribution assays including other antibiotics and can help elucidate the ADME of bitespiramycin.

Analysis of the effect of therapy for severe intracranial infection after craniotomy

ObjectiveTo retrospectively analyze the distribution characteristics of pathogenic bacteria in the cerebrospinal fluid (CSF) of patients with severe intracranial infection after craniotomy and treatment results. The aim was to provide a clinical basis and reference for improving treatment for severe intracranial infections. MethodsThis was a retrospective analysis of the distribution of pathogenic bacteria and the therapeutic effect for 43 patients who developed severe intracranial infections after craniotomy. All patients had positive CSF cultures and were treated in two hospitals in Beijing from May 2015 to May 2020. All patients received an intravenous injection of sensitive antibiotics combined with a CSF lateral ventricle catheter or lumbar cistern drainage. Antibiotic lavage treatment was administered through an external drain. ResultsThe CSF bacterial culture results for the 43 patients showed 34 single-strain infections (26 Gram-positive bacteria and 8 Gram-negative bacteria) and 9 multistrain infections. Fifty-two pathogenic strains were isolated, namely 32 Gram-positive bacteria (61.54%), 18 Gram-negative bacteria (34.61%), and 2 fungi (3.85%). After combined treatment, 29 patients (67.44%) were cured; treatment was effective for 7 patients (16.28%) and ineffective for 7 patients (16.28%). After 6 months of follow-up, the 36 surviving patients were cured of infection. The Glasgow Outcome Scale score results showed that 5 of the 36 (13.9%) patients had a persistent vegetative state; 13 (36.1%) had severe disability; 12 (33.3%) had moderate disability; and 6 (16.7%) had mild disability. ConclusionCSF pathogenic bacteria in patients with intracranial infection after craniotomy were mainly Gram-positive bacteria, primarily Staphylococcus epidermidis. A small number of patients had mixed bacterial infections. Owing to the presence of implanted devices in patients who underwent ventriculoperitoneal shunt surgery, the antibacterial therapeutic effect was worse than that for other types of postoperative infections. Therefore, when initial intravenous antibiotics are ineffective, the shunt device should be removed or replaced as soon as possible. When initial intravenous antibiotics are ineffective and severe intracranial infection occurs, a combined treatment plan should be adopted. That is, CSF drainage and antibiotic lavage should be performed cautiously with the intravenous injection of sensitive antibiotics. Our clinical data confirmed that postoperative neurosurgical infection could lead to different degrees of nerve dysfunction, which should be considered.

Pituitary adenoma with oculomotor cistern extension: membranous anatomy and clinical application.

The anatomical basis of pituitary adenomas (PAs) with oculomotor cistern (OC) extension as a growth corridor is overlooked in the literature. In this paper, the authors use the technique of epoxy sheet plastination to study the membranous structure of the OC and validate the results by retrospective analysis of patients with OC extension. Eighteen specimens were used to study the membranous anatomy surrounding the OC using the epoxy sheet plastination technique. Thirty-four patients with OC extension were retrospectively reviewed. The OC consisted of two thin membranous layers. The inner layer was extended by the arachnoid layer from the posterior fossa, and the lateral layer consisted of the dura mater sinking from the roof of the cavernous sinus. The oculomotor nerve is more likely to displace with a superolateral trajectory due to the weakness of the posterior dura and the relatively large space in the medial and posterior trajectories, which is consistent with the intraoperative observations. Among the anatomical factors that affect the PA by OC extension, we found that the relative position of the internal carotid artery (ICA) and posterior clinoid process may lead to the narrowing of the OC. Of 34 cases, 28 patients achieved total resection. Among 24 preoperative patients with oculomotor nerve palsy, 16 cases were relieved to varying degrees postoperatively. There was no ICA injury or severe intracranial infection found in any of the patients. Extension into the OC is influenced by two anatomical factors: a weak point in the dura in the posterior OC and a potential space beyond this region of the dura. Meticulous knowledge of the membranous anatomy in endoscopic endonasal surgery is required to safely and effectively resect PA with OC extension.

Perisellar Tumor Coexisting with Unruptured Cerebral Aneurysm: Single-Stage or Staged Surgery?

The coexistence of perisellar tumors and intracranial aneurysms was previously considered a rare phenomenon. In this study, we introduce our experience with surgical strategies for the treatment of such coexisting pathologies. This retrospective study reviews the medical records and intraoperative videos of patients with coexisting pathologies of perisellar tumors and aneurysms from Nov 2017 to Oct2022. Our study involved 20 patients, including 9 males and 11 females. Three patients selected the single-stage endoscopic endonasal approach (EEA), including one with a type of MP trigeminal schwannoma with an anterior communicating aneurysm, 1 with a pleomorphic xanthoastrocytoma with a left internal carotid artery paraclinoid aneurysm, and 1 with a recurrent pituitary adenoma with a right internal carotid artery paraclinoid aneurysm. Thirteen patients chose tumor resection first through the EEA with embolization or aneurysm conservation. There were also 2 patients with irregularly shaped aneurysms who chose embolization before tumor resection. All tumors were completely removed, with only a few patients experiencing recurrence and postoperative complications, and the follow-up of the aneurysms was also stable. There were also 2 patients who chose conservative management for both tumors and aneurysms, but unfortunately, one of them suffered from aneurysm rupture and eventually died. No cerebrospinal fluid rhinorrhea, severe intracranial infection, or surgical-related hemorrhage was found in any patients. Staged surgery or conservative treatment for aneurysms can be considered a safe and effective strategy for the treatment of coexisting pathologies. However, in very selected cases, the single-stage EEA can be used as part of a comprehensive treatment for such coexisting pathologies.

Research Progress of Rigid Skull Base Reconstruction after Transnasal Endoscopy

With the rapid development of diagnosis and treatment technology, equipment and instruments in the new era of neurosurgery, [1, 2] endoscope-assisted transnasal skull base surgery technology is becoming increasingly mature, surgical indications show an expanding trend, and the types of treated lesions are increasing day by day under the advantages of less trauma, quick recovery, high total resection rate and clear visual field exposure [3-5]. However, cerebrospinal fluid leakage and severe intracranial infection caused by the defect of skull base bone and dura mater have a great adverse impact on the prognosis of patients. Therefore, how to carry out long-lasting and effective skull base reconstruction after successful tumor resection is particularly important to reduce the occurrence of cerebrospinal fluid leakage after operation. Currently, there is no uniform standard for skull base reconstruction methods, which can be roughly divided into soft reconstruction and rigid reconstruction [6, 7]. There is no doubt about the importance of soft reconstruction in tissue water sealing, but rigid reconstruction of skull base is often ignored or even controversial [6]. In this paper, various techniques of skull base rigid reconstruction are reviewed, and the necessity of skull base rigid reconstruction is expounded.

Exploration of the causes of cerebrospinal fluid leakage after endoscopic endonasal surgery for sellar and suprasellar lesions and analysis of risk factors.

ObjectivePostoperative cerebrospinal fluid (CSF) leakage following endoscopic endonasal surgery (EES) is a frequent complication. This study aims to identify potential risk factors of postoperative CSF leakage.MethodsA retrospective review of 360 patients who underwent EES was included. The associations between postoperative CSF leakage and patient demographics, medical history, tumor characteristics, and intraoperative repair techniques were analyzed; the diagnosis and repair of postoperative CSF leakage were also introduced.ResultsPostoperative CSF leakage occurred in 14 patients (3.9%), 2 of them cured by lumbar cistern drainage, 12 underwent endoscopic repair. Among these 12 cases, 3 were repaired twice, and the rest were cured the first time. During the repair surgery, insufficient embedded fat was detected in one case detected, seven with breached inner artificial dura, three had vascularized pedicle nasoseptal flap (VP-NSF) displacement, two with VP-NSF perforation, two with VP-NSF inactivation, and one with imperfect adherence to VP-NSF to the skull base. Eight cases had intracranial infections. Excluding one case who died of severe intracranial infection, the rest were cured and discharged without obvious sequelae. Multivariate analysis revealed that the suprasellar lesion, subarachnoid invasion, and intraoperative grade 3 flow CSF leakage were the risk factors of CSF leakage after operation, while the bone flap was a protective factor.ConclusionBone flap combined with VP-NSF and iodoform gauze for skull base reconstruction is recommended in high-risk patients, while postoperative lumbar cistern drain remains dispensable.

Cranial extramedullary hematopoiesis with pancreatic secondary hemochromatosis in a beta thalassemia patient: A case report

Thalassemia is one of the most worrying hemolytic disorder with wide range of evolving clinical alterations based on the type, severity of affected hematopoietic mechanisms and repeated transfusions to correct underlying anemia.We present a 13 year old female patient diagnosed with thalassemia major showing features of cranial extra medullary hematopoiesis with severe intracranial infections in the form of cerebellar abscess and otomastoiditis extending in to adjacent sinus venouses, Iron deposition in liver & pancreas and incidental findings of uncomplicated horse shoe kidney.Extra medullary hematopoiesis is a catch up mechanism at the failing medullary hematopoeising to keep in check the hemoglobin levels without causing much physiological imbalance.EMH usually affects visceral structures like liver, spleen lymph nodes and thorax. Less commonly pleura, lungs, GIT, breast, skin, kidneys, adrenals and rarely the cranium and intracranial structures. Here, we present one of the rare presentations of cranial EMH in the background of severe intracranial infection.

Application of metagenomic next-generation sequencing for the diagnosis of intracranial infection of Listeria monocytogenes.

BackgroundIntracranial infection of Listeria monocytogenes (LM) can lead to various manifestations, including meningitis, meningoencephalitis, brainstem encephalitis, and brain abscess, which often have a poor prognosis. Metagenomic next-generation sequencing (mNGS) is a promising new tool for the diagnosis of intracranial infection of LM. We describe the typical clinical manifestations of LM intracranial infection and highlight its rarity and severity to help physicians better understand the disease characteristics.MethodsSix cases of severe LM intracranial infection were diagnosed by mNGS. We conducted a retrospective analysis of the data on disease progression, diagnostic tools, treatments, and outcomes, and summarized the findings. We compared the differences in diagnostic accuracy and timeliness between mNGS and etiological cultures.ResultsAmong the 6 patients, 5 were males and 1 was female (age range 32–83). Three patients had a history of immunosuppressive therapy. Common symptoms included fever (100%) and a stiff neck (100%). Coma occurred early in severe patients (66%). Two healthy young patients had previously developed with meningitis, while coma occurred in 3 immunosuppressed patients and 1 elderly patient. Three immunosuppressed patients presented with brain abscess, brainstem encephalitis, and meningitis. 1 elderly patient presented with meningitis. Two patients developed septic shock complications early. Laboratory data showed normal or slightly increased leukocytes, neutrophils, and procalcitonin, and cerebrospinal fluid (CSF) tests were consistent with bacterial CSF infection. All 6 patients were examined for blood culture and CSF culture. The positive rate of blood culture and CSF culture was 50% and 16%. The average time from admission to positive culture findings was 91 h. All 6 patients were examined for CSF mNGS. Two were also examined for whole-blood mNGS. The positive rate for CSF mNGS and whole-blood mNGS results was 100%. The mean time from admission to positive mNGS report was 47 h. After diagnosis and treatment with sensitive antibiotics, 1 patient with brain abscess developed neurological sequelae, while the other 5 patients completely recovered.ConclusionsmNGS can improve accuracy in the diagnosis of LM intracranial infection and reduce the delay in diagnosis. Intracranial infection of Listeria monocytogenes responds well to the timely use of appropriate antibiotics.

Efficacy and safety of intraventricular polymyxin B plus continuous ventricular drainage for the treatment of intracranial infection caused by drug-resistant Acinetobacter baumannii.

The bacterial resistance rate has risen in recent years, and polymyxin B has been used more frequently to treat severe intracranial infection. This study aimed to investigate the clinical efficacy and safety profiles of intraventricular polymyxin B plus continuous ventricular drainage for the treatment of intracranial infection caused by drug-resistant Acinetobacter baumannii (DR-AB). A retrospective study was performed on 21 patients who had an intracranial infection caused by DR-AB after neurosurgery at our hospital from May 2017 to July 2020. These patients were treated by intraventricular polymyxin B plus continuous ventricular drainage. The clinical features, treatment, cerebrospinal fluid (CSF)-related indicators, outcomes, and prognosis of these patients were analyzed. The external drainage tubes inserted into the lateral ventricle were kept unobstructed in all 21 patients. These patients received intraventricular polymyxin B 5 mg/day plus intravenous antibiotics. The treatment with intraventricular polymyxin B lasted for 18.19±12.36 days. The time to positive CSF culture was 10.50±10.60 days. The bacterial clearance rate of CSF was 95.2% (20/21). The clinical cure rate was 81.0% (17/21), and the mortality rate was 19.0% (4/21). As for the causes of death, 1 case died from purulent CSF with cerebral abscess, which was considered to be caused by extensive brain parenchymal infection, 2 cases died from spontaneous intraventricular hemorrhage after returning negative for CSF cultures, and 1 case died from secondary massive cerebral infarction after returning negative for CSF cultures. There were no significant changes in the serum creatinine level before and after treatment. For intracranial infection caused by DR-AB, early intraventricular polymyxin B plus continuous ventricular drainage could effectively clear the drug-resistant bacteria from CSF, thereby improving efficacy and reducing mortality. Renal functions before and after treatment were not changed significantly, proving that this combined treatment was safe and effective.

Penicillium chrysogenum

Brain abscess is a severe intracranial infection with a very high mortality rate and usually secondary to an external infection. Fungal infections are now been increasingly reported especially with Candida sp. We present a case of brain abscess in a 63-year-old woman, which was managed successfully by surgical evacuation and was diagnosed radiologically as a fungal infection and on culture detected to have Penicillium chrysogenum.

Clinical study on endoscopic surgery for soft tissue necrosis of cranial base after radiotherapy for nasopharyngeal carcinoma

Objective: To investigate the diagnosis and surgical treatment of patients with soft tissue necrosis of cranial base after radiotherapy for nasopharyngeal carcinoma (NPC). Methods: The clinical data of 7 NPC patients with soft tissue necrosis but not bone necrosis after radiotherapy were retrospectively analyzed.They were treated in Xiangya Hospital from 2015 to 2019. The clinical manifestations, diagnosis, treatment and prognosis were analyzed. The major clinical symptoms of the 7 patients were headache in 7 cases, hearing loss in 7 cases, long-term nasal malodor in 5 cases and epistaxis in 2 cases. All patients underwent high-resolution CT, MR and magnetic resonance angiography (MRA) before operation. All cases were treated with extended transnasal endoscopic approach under general anesthesia for resection of necrotic tissue. Five cases had their affected cartilaginous segments of the eustachian tubes partially or completely resected, 7 cases were treated with myringotomy and tube insertion, and 1 case was treated with pansinusectomy. Anti-inflammatory treatment were carried out during the perioperative period. The recovery of patients was observed and recorded through regular follow-up (from 6 months to 3 years) after the operation. Results: Nasopharynx soft tissue lesions can be seen in seven patients with bone cortex integrity by CT, and small bubble shadow can be seen at junction area between skull base soft tissue lesions and skull base bone surface.MR and MRA examination showed extensive inflammatory changes of nasopharynx. Parapharyngeal irregular necrotic cavity was found in 6 cases without central enhancement, demonstrating edema of surrounding soft tissue. The necrotic tissue of all 7 patients was surgically removed. Postoperative pathological examinations confirmed that all of them were necrotic soft and cartilaginous tissue, without tumor recurrence. The symptoms of all patients were significantly alleviated after operation. Headache was cured in 5 cases and relieved in 2 cases. Nasal malodor was cured in 4 cases and alleviated in 1 case. During the follow-up period, 5 patients survived, and 2 patients who had their eustachian tube reserved died. One of them died of nasopharyngeal hemorrhage caused by recurrent nasopharyngeal necrosis 3 months after the operation. Another case died of severe intracranial infection 6 months after operation. Conclusions: The diagnosis of skull base soft tissue necrosis after radiotherapy for nasopharyngeal carcinoma needs comprehensive analysis of radiotherapy history, clinical manifestations and imaging examination. High resolution CT, MR and MRA of skull base are very important for diagnosis. Early active removal of large-scale necrotic lesions under endoscope and partial or total resection of eustachian tube cartilage according to the involvement of eustachian tube cartilage is effective means of controling skull base soft tissue necrosis after radiotherapy. The effective means of necrosis can improve the quality of life of patients.

Multiple brain abscesses and ventriculitis secondary to chronic periodontitis.

Chronic marginal periodontitis is a common oral disease, but can in rare cases cause severe intracranial infection. This case illustrates that poor dental status can be life threatening, in particular for immunocompromised patients.

Sequential intraventricular injection of tigecycline and polymyxin B in the treatment of intracranial Acinetobacter baumannii infection after trauma: a case report and review of the literature

BackgroundIntracranial infection after craniotomy is one of the most serious postoperative complications, especially multidrug-resistant (MDR) or extensively drug-resistant (XDR) bacterial meningitis, and strongly affects the prognosis of patients. Current treatment experience regarding these infections is scarce.Case presentationWe report a case of severe intracranial infection of XDR Acinetobacter baumannii (A. baumannii) that was treated by intravenous (IV) injection, sequential intraventricular (IVT) injection of tigecycline and polymyxin B, and other anti-infective drugs. Good results were obtained, and the patient was eventually discharged from the hospital. This case is characterized by intracranial infection.ConclusionsThe polymyxin B IV + IVT pathway is an ideal treatment strategy for XDR A. baumannii. The tigecycline IVT pathway is also a safe treatment option.

Delayed diagnosis of X-linked agammaglobulinaemia in a boy with recurrent meningitis

BackgroundX-linked agammaglobulinaemia (XLA) is a rare inherited primary immunodeficiency disease characterized by the B cell developmental defect, caused by mutations in the gene coding for Bruton’s tyrosine kinase (BTK), which may cause serious recurrent infections. The diagnosis of XLA is sometimes challenging because a few number of patients have higher levels of serum immunoglobulins than expected. In this study, we reported an atypical case with recurrent meningitis, delayed diagnosis with XLA by genetic analysis at the second episode of meningitis at the age of 8 years.Case reportAn 8-year-old Chinese boy presented with fever, dizziness and recurrent vomiting for 3 days. The cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) results were suggestive of bacterial meningoencephalitis, despite the negative gram staining and cultures of the CSF. The patient was treated with broad-spectrum antibiotics and responded well to the treatment. He had history of another episode of acute pneumococci meningitis 4 years before. The respective level of Immunoglobulin G (IgG), Immunoglobulin A (IgA) and Immunoglobulin M (IgM) was 4.85 g/L, 0.93 g/L and 0.1 g/L at 1st episode, whereas 1.9 g/L, 0.27 g/L and 0 g/L at second episode. The B lymphocytes were 0.21 and 0.06% of peripheral blood lymphocytes at first and second episode respectively. Sequencing of the BTK coding regions showed that the patient had a point mutation in the intron 14, hemizyous c.1349 + 5G > A, while his mother had a heterozygous mutation. It was a splice site mutation predicted to lead to exon skipping and cause a truncated BTK protein.ConclusionImmunity function should be routinely checked in patients with severe intracranial bacterial infection. Absence of B cells even with normal level of serum immunoglobulin suggests the possibility of XLA, although this happens only in rare instances. Mutational analysis of BTK gene is crucial for accurate diagnosis to atypical patients with XLA.

Clinical application of the detection of heparin-binding protein in cerebrospinal fluid in intracranial infectious diseases

Objective To investigate the clinical application value of the levels of heparin- binding protein (HBP) in cerebrospinal fluid (CSF) for intracranial infectious diseases. Methods A case-control study was conducted. 150 patients after craniotomy(73 in the postoperative bacterial intracranial infection group, 77 in the postoperative non-infection group) admitted to the Department of Neurology of the People′s Hospital of Liaoning Province from December 2016 to May 2018 were collected. At the same time, 46 patients without operation (14 in the non-bacterial intracranial infection group, 32 patients without intracranial infection were selected as control group whose white blood cell count (WBC) values in CSF were all below 10×106/L) in the same period were also collected. According to the diagnostic criteria for severe intracranial infection, the patients with bacterial intracranial infection were divided into 26 cases of mild intracranial infection group and 47 cases of severe intracranial infection group. According to the Glasgow Outcome Scale (GOS) score at the time of discharge, the patients were divided into 30 cases of good prognosis group (GOS score 4-5 points) and 43 cases of poor prognosis group (GOS score 1-3 points). The concentrations of HBP in CSF were tested with latex immunoturbidimetry, and the concentrations of procalcitonin(PCT) in cerebrospinal fluid and serum were tested with electrochemiluminescence, and cerebrospinal fluid routine were tested with instrument method, and the concentrations of total protein(TP) in cerebrospinal fluid were tested with turbidimetry. The differences of the laboratory test indicators in each group were statistically analyzed, and the levels of HBP in CSF of patients with different degrees of intracranial infection and different prognosis were compared. Comparison of two independent samples was performed using the Mann-Whitney U test. Results The HBP levels in cerebrospinal fluid were 187.00 (73.00, 635.00) ng/ml, 10.00 (3.50, 32.00) ng/ml, 1.50 (0, 4.00) ng/ml, 3.00 (1.00, 4.00) ng/ml in post-craniotomy bacterial intracranial infection group, uninfected group after craniotomy, non-bacterial intracranial infection group and control group respectively. The cerebrospinal fluid levels of WBC count were 1 280.00 (363.00, 4 327.00)×106/L, 63.00 (18.50, 300.00)×106/L, 5.00 (3.00, 14.75)×106/L, 3.00 (2.00, 5.75)×106/L. The absolute value of cerebrospinal fluid neutrophils were 1 216.00 (225.50, 3 895.50)×106/L, 24.00 (2.00, 209.50)×106/L, 1.00 (1.00, 3.00)×106/L, 1.00 (1.00, 1.00)×106/L. The cerebrospinal fluid levels of PCT were 0.16 (0.10, 0.32) ng/ml, 0.09 (0.07, 0.14) ng/ml, 0.07 (0.06, 0.12) ng/ml, 0.07 (0.06, 0.13) ng/ml. The serum levels of PCT were 0.36 (0.15, 1.09) ng/ml, 0.09 (0.04, 0.16) ng/ml, 0.08 (0.04, 0.13) ng/ml, 0.07 (0.03, 0.11) ng/ml. The levels of HBP, WBC, neutrophils, PCT in CSF and serum PCT in the post-craniotomy bacterial intracranial infection group were significantly higher than those in the uninfected group after craniotomy (Z=-9.246,-6.759,-6.741,-4.477,-6.202, P 0.05)between the uninfected group after craniotomy and the non-bacterial intracranial infection group. There were significant differences in the levels of HBP, WBC and neutrophils in CSF(Z=-4.496, -6.685, -4.842, P 0.05)between the uninfected group after craniotomy and the control group. There were no significant differences in the levels of HBP, PCT in CSF and serum PCT (Z=-0.861,-0.514,-0.273, P>0.05)and significant differences in the levels of WBC and neutrophils in CSF(Z=-2.756, -3.060, P<0.05) between the non-bacterial intracranial infection group and the control group. The levels of HBP in CSF in the severe intracranial infection group were significantly higher than those in the mild intracranial infection group(Z=-6.267, P<0.05). The levels of HBP in CSF in the poor prognosis group were significantly higher than those in the good prognosis group(Z=-7.064, P<0.05). The area under the ROC curve for the diagnosis of bacterial intracranial infection by HBP, WBC, neutrophils, TP, PCT in CSF and PCT in serum was 0.986, 0.987, 0.945, 0.945, 0.770 and 0.914, respectively. The area under the ROC curve for differential diagnosis of bacterial intracranial infection and non-bacterial intracranial infection was 0.994, 0.958, 0.961, 0.929, 0.747 and 0.936, respectively. Conclusions HBP in CSF is an ideal indicator for the diagnosis of bacterial intracranial infection. It is important to distinguish between bacterial intracranial infection and non-bacterial intracranial infection. The extent of increase is related to the severity of infection and prognosis of the disease. Key words: Heparin-binding protein; Cerebrospinal fluid; Intracranial infection

Repeated Transfusion of Granulocytes to Control Multidrug-Resistant Pseudomonas Aeruginosa Sepsis in Haploidentical Hematopoietic Stem Cell Transplant Patients during Pre-Engraftment Stage

Background and Objectives: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for treating pediatric hematological malignancies that are refractory to other therapies. However, severe infections in neutropenic patients remain the major cause of morbidity and mortality, as well as influence the engraftment during HSCT. Multidrug-resistance (MDR) pseudomonas aeruginosa sepsis during the pre-engraftment stage has a highly prevalence of mortality, especially in patients with the primary infection site at the facial dangerous triangle. Without the efficient and time treatment, the bacterium may readily spread into the brain, causing severe intracranial infection and even death. There is an urgent need to effectively control MDR-pseudomonas aeruginosa infection and reduce the mortality of patients undergoing allo-HSCT.Method: We report herein a 5-year-old boy with acquired severe aplastic anemia (SAA) who experienced a secondary engraftment failure eight months after receiving haploidentical HSCT from his father. Owing to recurrent fever and severe pneumonia during persistent neutropenia, the patient received second transplant using bone marrow cells from his farther. Two days after the secondary transplant bloodstream identified an infection of MDR-pseudomonas aeruginosa accompanied with symptoms of chills and high fever, and deteriorating pneumonia. On day +4 he had a cellulitis at facial dangerous triangle with lacrimal gland and nasolacrimal duct involved, and secretion culture also confirmed the same bacteria. He was given antibiotics of Tetracycline, Levofloxacin, and Cefoperazone schubatam. However, the involved skin became worse and high fever peak became more frequent, suggesting the progression of sepsis. To facilitate the reconstitution of granulocytes in the patient, we performed six doses of granulocyte transfusion (GTX) from father once every over a period of six days. Granulocyte counts were performed every 12 hours after transfusion in order to maintain a level of granulocyte more than 0.5×109/L. Blood typing showed that the patient was type A and the farther was type AB. To avoid a possible hemolysis due to ABO-mismatched, we treated granulocytes with hydroxyethyl starch before transfusion.Results: During GTXs (from day +6 to +11 after transfusion), the patient's body temperature fluctuated between 37.0℃-38.2℃. There were no signs and symptoms of exacerbated pneumonia, such as cough, hemoptysis and moist rale. We didn't observe transfusion related acute lung injury (TRALI) and respiratory failure. The urine was clear without hematuria. The area of skin involved became under control. Notably, the patient had granulocyte engrafted on day +15 after transfusion, decrease of body temperature on day +16 and normal temperature on day +20. Concurrently, the facial cellulitis was gradually narrowing and moist rale of the lung disappeared. A repeat chest CT scan confirmed disappearance of the infection site in the lung. The bloodstream culture was negative on day +9 and secretion culture was negative on day +15. We maintained the treatment with antibiotics until the negative blood culture was confirmed twice. Eleven months after the treatment, the patient is alive with full donor chimaerism. His blood type becomes AB type. Other tests, including peripheral blood cell counts, liver and renal functions as well as pulmonary function, are all normal.Conclusion: Multidrug-resistant bacteria infection is a common and yet fatal complication in SAA patients. These patients usually experience a prolonged period of neutropenia when undergoing HSCT. We demonstrate here that when being combined with the utilization of broad spectrum antibiotics, repeated GTXs from donor source prove to be an effective therapy for controlling these infections, thereby reducing early death and improving successful rate of allo-HSCT. Therefore, GTXs are recommended as, at best, a “bridge” procedure, that may protect the patient from fatal infections until myeloid recovery ensues DisclosuresNo relevant conflicts of interest to declare.

Clinical analysis and prognosis of children with neuroblastoma with pancreatic infiltration

Objective To summarize the clinical data and characteristics of neuroblastoma (NB) with pancrea-tic infiltration and to assess the clinical features and the prognosis of NB. Methods According to NB protocol at Beijing Children′s Hospital, Capital Medical University(BCH-NB-2007), based on Hong Kong NB protocol, the patients were divided into 3 groups of low-risk (LR) group, medium risk (MR) group and high-risk (HR) group.All children were followed up till March 31, 2017.Diagnosis of pancreatic infiltration of NB was made by abdominal enhancement of CT, enhanced magnetic resonance imaging (MRI) or 18-fluorodeoxyglucose-positron emission tomography-computed tomography(18F-FDG-PET/CT), any of which could suggest NB pancreatic infiltration or postoperative pathology prompted NB to infiltrate the pancreas.Retrospective summary and analysis of indicators were performed, which included the initial diagnosis of primary tumor and metastatic tumor site, tumor markers, clinical stage, risk group, imaging features and treatment. Results (1)Totally 50 eligible patients were included: 27 females, 23 males, median age of 33 months (7-129 months), 10 cases ≤18 months, 40 cases>18 months; 3 cases were of International Neuroblastoma Staging System(INSS)-Ⅲ, 47 cases of INSS-Ⅳ; 2 caes of LR, 3 cases of MR, 45 cases of HR; 28 cases had a fever, 27 cases with abdominal mass, 14 cases with abdominal pain, 9 cases with limb pain, 5 cases with vomiting, 4 cases with diarrhea, and 1 case with jaundice.Forty-nine cases of primary tumor were located in the retroperitoneal adrenal gland, and 1 case in the pelvic cavity.Thirty-two cases had tumor diameter≥10 cm.(2)Tumor markers and imaging features: the median serum lactate dehydrogenase(LDH) value in 50 cases was 669 U/L(263-6 762 U/L), of them 19 cases >1 000 U/L.A total of 80% cases had neuron specific enolase(NSE) >0.15 ng/L.Nine cases had elevated amylase (AMY), and 7 cases had elevated lippase (LPS), and all the levels were elevated in 5 cases.A total of 41 cases had pancreas infiltration by abdominal ultrasound, 44 cases had pancreas infiltration by abdominal enhancement computed tomography (CT), 100%(14/14 cases)of pancreas infiltration was confirmed by abdominal reconstruction enhancement nuclear imaging MRI, and NB pancreas infiltration was proved in 41.3%(19/46 cases)by 18F-FDG-PET/CT.Comparison of the above 4 imaging studies: one imaging examination index was positive in 7 cases, accounting for 14.0%, 2 positive in 26 cases, accounting for 52.0%, 3 positive in 15 cases, accounting for 30.0%, and 4 positive in 2 cases, accounting for 4.0%.(3)Treatment outcomes: totally 50 cases received treatment, including 2 cases of LR, all cases were of INSS-Ⅲ, and 1 case with complete remission (CR). Three cases of MR belonging to INSS-Ⅳ had complete resection of the tumor, 1 case had recurrence and died, and the other two were stable.Forty-five cases with HR, median follow-up lasting for 15 (4-53) months, 16 cases had occurrence(35.6%), 3 cases were relapsed after stopping treatment for 2, 3, 18 months, respectively; tumor progressed in 12 patients during treatment, and 1 case got severe intracranial infection and gave up treatment before death.Kaplan-Meier analysis showed the expected 3-year event free survival(EFS) rate was 22.1%, and 3-year overall survival(OS) rate was 38.5%. Conclusions Preliminary results show that 90% with pancreatic infiltration of NB belong to Ⅳ HR group of children, and almost primary tumor is almost located in the retroperitoneal ragion.NB with pancreatic infiltration clinical manifestations is hidden and nonspecific.More than half of the children have no obvious abdominal pain or vomiting, and so imaging examination is needed to determine the situation of pancreatic metastasis further.Abdominal reconstruction enhancement MRI has a high sensitivity and specificity for pancreatic metastatic lesions, which can be used as the basis for early diagnosis.The overall prognosis is poor.The expected 3-year EFS rate can be 22.1%, 3-year OS rate was 38.5%. Key words: Neuroblastoma; Pancreatic infiltration; Clinical feature; Child

Abstract TMP104: Stroke in Paediatric Bacterial Meningitis

Introduction: Bacterial meningitis is a severe intracranial infection with a high complication rate. Neurological morbidity relates to parenchymal involvement where vascular mechanisms and stroke may predominate. Here, we systematically identified all neonates and children with bacterial meningitis and compared those with and without MRI-confirmed stroke. We hypothesized that patterns of stroke would correlate with causative organism and neurological outcome. Methods: Population-based (2.2 million), ten-year retrospective (2002-2012) cross-sectional study in Southern Alberta, Canada. Inclusion criteria were: (1) age from newborn (including prematurity) to 18 years, (2) brain MRI including DWI during admission, and (3) laboratory confirmed acute bacterial meningitis. Demographics, clinical presentations, risk factors, and laboratory findings were extracted. Original imaging was blindly reviewed and classified for stroke and injury pattern. Outcomes were extrapolated to the Pediatric Stroke Outcome Measure (PSOM). Results: Twenty-four patients had confirmed bacterial meningitis and acute MRI (6 neonates, 83% male, and 18 children, mean age 3.14+/-3.9 years, 67% male). Arterial ischemic stroke was confirmed in 9/24 (38%). Strokes were often multifocal (89%), particularly in neonates (100%). Subjects with stroke were more likely to have longer duration of illness prior to presentation, meningismus, prolonged fever, seizures, and new focal neurological signs. The most common organisms were S. pneumonia in older children (44%) and group B streptococcus in neonates (33%). Three patients received steroids, 3 ASA and 1 heparin and ASA. Mortality was 22% in children with stroke and zero in those without (p=0.16). Survivors with stroke were more likely to have motor deficit (71% vs. 25%, p = 0.07), cognitive deficit (75% vs. 38%, p = 0.5), and speech deficit (60% vs. 10%, p = 0.08). Conclusions: More than a third of children with bacterial meningitis warranting MRI have stroke. Associations include longer duration of illness, meningismus, focal neurological signs and common causative organisms. Stroke was associated with higher mortality and morbidity, warranting consideration of increased MRI screening and new approaches to treatment.

Seizure increases electroencephalographic abnormalities in children with tuberculous meningitis

Background&lt;br /&gt;Tuberculous meningitis (TBM) is a severe intracranial infection with fatal outcomes, permanent disabilities, and electroencephalographic (EEG) abnormalities. Seizures may occur in TBM. The EEG findings in TBM vary according to the site of the inflammatory process. There are few studies describing the EEG patterns and clinical manifestations of TBM. The objective of this study was to investigate the correlation between clinical findings and EEG patterns in children with TBM. &lt;br /&gt;&lt;br /&gt;Methods&lt;br /&gt;A study of cross-sectional design using medical records was conducted on 12 children with TBM, with their EEG patterns classified as abnormal and normal. Clinical manifestations such as seizures, altered consciousness, headache or fever were collected. A positive cerebrospinal fluids Mycobacterium tuberculosis culture was considered to indicate definitive TBM. Abnormal EEG descriptions were classified into abnormal I, II or III. Correlation between EEG pattern and clinical manifestation were analyzed with Fisher’s exact test. &lt;br /&gt;&lt;br /&gt;Results&lt;br /&gt;The study found cases of 12 children with TBM, the majority presenting with seizures, decreased consciousness and fever. Abnormal EEGs were found in 75% of children and 77% of them showed epileptogenic activities. The EEG results mostly described epileptogenic potentials in the frontotemporal region. There was a significant correlation between EEG abnormality and seizures in children with TBM (p&amp;lt;0.05).&lt;br /&gt;&lt;br /&gt;Conclusions&lt;br /&gt;The EEG pattern in children with TBM varies, and EEG abnormalities were more frequently localized in the frontotemporal region. Seizures were associated with EEG abnormalities in children with TBM. EEG abnormalities occurring simultaneously with seizures may predict the occurrence of seizures.