Task-based EEG and fMRI paradigms in a multimodal clinical diagnostic framework for disorders of consciousness.

Disorders of consciousness (DoC) are generally diagnosed by clinical assessment, which is a predominantly motor-driven process and accounts for up to 40 % of non-communication being misdiagnosed as unresponsive wakefulness syndrome (UWS) (previously known as prolonged/persistent vegetative state). Given the consequences of misdiagnosis, a more reliable and objective multimodal protocol to diagnosing DoC is needed, but has not been produced due to concerns regarding their interpretation and reliability. Of the techniques commonly used to detect consciousness in DoC, task-based paradigms (active paradigms) produce the most unequivocal result when findings are positive. It is well-established that command following (CF) reliably reflects preserved consciousness. Task-based electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) can detect motor-independent CF and reveal preserved covert consciousness in up to 14 % of UWS patients. Accordingly, to improve the diagnostic accuracy of DoC, we propose a practical multimodal clinical decision framework centered on task-based EEG and fMRI, and complemented by measures like transcranial magnetic stimulation (TMS-EEG).

The Molecular Landscape of Primary CNS Lymphomas (PCNSLs) in Children and Young Adults.

Pediatric brain tumors are often noted to be different from their adult counterparts in terms of molecular features. Primary CNS lymphomas (PCNSLs) are mostly found in elderly adults and are uncommon in children and teenagers. There has only been scanty information about the molecular features of PCNSLs at a young age. We examined PCNSLs in 34 young patients aged between 7 and 39 years for gene rearrangements of BCl2, BCL6, CCND1, IRF4, IGH, IGL, IGK, and MYC, homozygous deletions (HD) of CDKN2A, and HLA by FISH. Sequencing was performed using WES, panel target sequencing, or Sanger sequencing due to the small amount of available tissues. The median OS was 97.5 months and longer than that for older patients with PCNSLs. Overall, only 14 instances of gene rearrangement were found (5%), and patients with any gene rearrangement were significantly older (p = 0.029). CDKN2A HD was associated with a shorter OS (p < 0.001). Only 10/31 (32%) showed MYD88 mutations, which were not prognostically significant, and only three of them were L265P mutations. CARD11 mutations were found in 8/24 (33%) cases only. Immunophenotypically, the cases were predominantly GCB, in contrast to older adults (61%). In summary, we showed that molecular findings identified in the PCNSLs of the older patients were only sparingly present in pediatric and young adult patients.

Case Report: Taxifolin for neurosurgery-associated early-onset cerebral amyloid angiopathy.

Cases of iatrogenic cerebral amyloid angiopathy (CAA) have been increasingly reported recently, particularly those associated with neurosurgery. Preclinical studies have shown taxifolin to be promising for treating CAA. We describe a young 42-year-old man with a history of childhood traumatic brain injury that required a craniotomy for hematoma evacuation. He later presented with recurrent lobar intracerebral hemorrhage (ICH) decades later, which was histologically confirmed to be CAA. Serial 11C-Pittsburgh compound B positron emission tomography (11C-PiB-PET) imaging showed a 24% decrease in global standardized uptake value ratio (SUVR) at 10 months after taxifolin use. During this period, the patient experienced clinical improvement with improved consciousness and reduced recurrent ICH frequency, which may be partly attributable to the potential amyloid-ß (Aß) clearing the effect of taxifolin. However, this effect seemed to have diminished at 15 months, CAA should be considered in young patients presenting with recurrent lobar ICH with a history of childhood neurosurgery, and serial 11C-PiB-PET scans warrant further validation as a strategy for monitoring treatment response in CAA for candidate Aß-clearing therapeutic agents such as taxifolin.

Machine learning-based prediction of COVID-19 mortality using immunological and metabolic biomarkers.

COVID-19 mortality prediction Background COVID-19 has become a major global public health problem, despite prevention and efforts. The daily number of COVID-19 cases rapidly increases, and the time and financial costs associated with testing procedure are burdensome. Method To overcome this, we aim to identify immunological and metabolic biomarkers to predict COVID-19 mortality using a machine learning model. We included inpatients from Hong Kong's public hospitals between January 1, and September 30, 2020, who were diagnosed with COVID-19 using RT-PCR. We developed three machine learning models to predict the mortality of COVID-19 patients based on data in their electronic medical records. We performed statistical analysis to compare the trained machine learning models which are Deep Neural Networks (DNN), Random Forest Classifier (RF) and Support Vector Machine (SVM) using data from a cohort of 5,059 patients (median age = 46 years; 49.3% male) who had tested positive for COVID-19 based on electronic health records and data from 532,427 patients as controls. Result We identified top 20 immunological and metabolic biomarkers that can accurately predict the risk of mortality from COVID-19 with ROC-AUC of 0.98 (95% CI 0.96-0.98). Of the three models used, our result demonstrate that the random forest (RF) model achieved the most accurate prediction of mortality among COVID-19 patients with age, glomerular filtration, albumin, urea, procalcitonin, c-reactive protein, oxygen, bicarbonate, carbon dioxide, ferritin, glucose, erythrocytes, creatinine, lymphocytes, PH of blood and leukocytes among the most important biomarkers identified. A cohort from Kwong Wah Hospital (131 patients) was used for model validation with ROC-AUC of 0.90 (95% CI 0.84-0.92). Conclusion We recommend physicians closely monitor hematological, coagulation, cardiac, hepatic, renal and inflammatory factors for potential progression to severe conditions among COVID-19 patients. To the best of our knowledge, no previous research has identified important immunological and metabolic biomarkers to the extent demonstrated in our study. Supplementary Information: The online version contains supplementary material available at 10.1186/s44247-022-00001-0.

Repeat resection for recurrent glioblastoma in the temozolomide era: a real-world multi-centre study.

INTRODUCTION: In contrast to standard-of-care treatment of newly diagnosed glioblastoma, there is limited consensus on therapy upon disease progression. The role of resection for recurrent glioblastoma remains unclear. This study aimed to identify factors for overall survival (OS) and post-progression survival (PPS) as well as to validate an existing prediction model. METHODS: This was a multi-centre retrospective study that reviewed consecutive adult patients from 2006 to 2019 that received a repeat resection for recurrent glioblastoma. The primary endpoint was PPS defined as from the date of second surgery until death. RESULTS: 1032 glioblastoma patients were identified and 190 (18%) underwent resection for recurrence. Patients that had second surgery were more likely to be younger (<70 years) (adjusted OR: 0.3; 95% CI: 0.1-0.6), to have non-eloquent region tumours (aOR: 1.7; 95% CI: 1.1-2.6) and received temozolomide chemoradiotherapy (aOR: 0.2; 95% CI: 0.1-0.4). Resection for recurrent tumour was an independent predictor for OS (aOR: 1.5; 95% CI: 1.3-1.7) (mOS: 16.9 months versus 9.8 months). For patients that previously received temozolomide chemoradiotherapy and subsequent repeat resection (137, 13%), the median PPS was 9.0 months (IQR: 5.0-17.5). Independent PPS predictors for this group were a recurrent tumour volume of >50cc (aOR: 0.6; 95% CI: 0.4-0.9), local recurrence (aOR: 1.7; 95% CI: 1.1-3.3) and 5-ALA fluorescence-guided resection during second surgery (aOR: 1.7; 95% CI: 1.1-2.8). A National Institutes of Health Recurrent Glioblastoma Multiforme Scale score of 0 conferred an mPPS of 10.0 months, a score of 1-2, 9.0 months and a score of 3, 4.0 months (log-rank test, p-value < 0.05). CONCLUSION: Surgery for recurrent glioblastoma can be beneficial in selected patients and carries an acceptable morbidity rate. The pattern of recurrence influenced PPS and the NIH Recurrent GBM Scale was a reliable prognostication tool.

Patterns of care and survival of Chinese glioblastoma patients in the temozolomide era: a Hong Kong population-level analysis over a 14-year period.

Background: The aim of this study is to address the paucity of epidemiological data regarding the characteristics, treatment patterns and survival outcomes of Chinese glioblastoma patients. Methods: This was a population-level study of Hong Kong adult (>18 years) Chinese patients with newly diagnosed histologically confirmed glioblastoma between 2006 and 2019. The age standardized incidence rate (ASIR), patient-, tumor- treatment-related characteristics, overall survival (OS) as well as its predictors were determined. Results: One thousand and ten patients with a median follow-up of 10.0 months were reviewed. The ASIR of glioblastoma was 1.0 per 100 000 population with no significant change during the study period. The mean age was 57 + 14 years. The median OS was 10.6 months (IQR: 5.2-18.4). Independent predictors for survival were: Karnofsky performance score >80 (adjusted OR: 0.8; 95% CI: 0.6-0.9), IDH-1 mutant (aOR: 0.7; 95% CI: 0.5-0.9) or MGMT methylated (aOR: 0.7; 95% CI: 0.5-0.8) glioblastomas, gross total resection (aOR: 0.8; 95% CI: 0.5-0.8) and temozolomide chemoradiotherapy (aOR 0.4; 95% CI: 0.3-0.6). Despite the significant increased administration of temozolomide chemoradiotherapy from 39% (127/326) of patients in 2006-2010 to 63% (227/356) in 2015-2019 (P-value < .001), median OS did not improve (2006-2010: 10.3 months vs 2015-2019: 11.8 months) (OR: 1.1; 95% CI: 0.9-1.3). Conclusions: The incidence of glioblastoma in the Chinese general population is low. We charted the development of neuro-oncological care of glioblastoma patients in Hong Kong during the temozolomide era. Although there was an increased adoption of temozolomide chemoradiotherapy, a corresponding improvement in survival was not observed.

Epidemiological characteristics and genetic alterations in adult diffuse glioma in East Asian populations.

Understanding the racial specificities of diseases-such as adult diffuse glioma, the most common primary malignant tumor of the central nervous system-is a critical step toward precision medicine. Here, we comprehensively review studies of gliomas in East Asian populations and other ancestry groups to clarify the racial differences in terms of epidemiology and genomic characteristics. Overall, we observed a lower glioma incidence in East Asians than in Whites; notably, patients with glioblastoma had significantly younger ages of onset and longer overall survival than the Whites. Multiple genome-wide association studies of various cohorts have revealed single nucleotide polymorphisms associated with overall and subtype-specific glioma susceptibility. Notably, only 3 risk loci-5p15.33, 11q23.3, and 20q13.33-were shared between patients with East Asian and White ancestry, whereas other loci predominated only in particular populations. For instance, risk loci 12p11.23, 15q15-21.1, and 19p13.12 were reported in East Asians, whereas risk loci 8q24.21, 1p31.3, and 1q32.1 were reported in studies in White patients. Although the somatic mutational profiles of gliomas between East Asians and non-East Asians were broadly consistent, a lower incidence of EGFR amplification in glioblastoma and a higher incidence of 1p19q-IDH-TERT triple-negative low-grade glioma were observed in East Asian cohorts. By summarizing large-scale disease surveillance, germline, and somatic genomic studies, this review reveals the unique characteristics of adult diffuse glioma among East Asians, to guide clinical management and policy design focused on patients with East Asian ancestry.

Development of the SAFETEA Scores for Predicting Risks of Complications of Preventive Endovascular or Microneurosurgical Intracranial Aneurysm Occlusion.

OBJECTIVE: Preventive unruptured intracranial aneurysm occlusion can reduce the risk of subarachnoid hemorrhage, but both endovascular and microneurosurgical treatment carry a risk of serious complications. To improve individualized management decisions, we developed risk scores for complications of endovascular and microneurosurgical treatment based on easily retrievable patient, aneurysm, and treatment characteristics. METHODS: For this multicenter cohort study, we combined individual patient data from unruptured intracranial aneurysm patients ≥18 years undergoing preventive endovascular treatment (standard, balloon-assisted or stent-assisted coiling, Woven EndoBridge-device, or flow-diverting stent) or microneurosurgical clipping at one of 10 participating centers from three continents between 2000-2018. The primary outcome was death from any cause or clinical deterioration from neurological complications ≤30 days. We selected predictors based on previous knowledge about relevant risk factors and predictor performance and studied the association between predictors and complications with logistic regression. We assessed model performance with calibration plots and concordance (c) statistics. RESULTS: Of 1282 included patients, 94 (7.3%) had neurological symptoms that resolved <30 days, 140 (10.9%) had persisting neurological symptoms, and 6 died (0.5%)). At 30 days, 52 patients (4.1%) were dead or dependent. Predictors of procedural complications were: size of aneurysm, aneurysm location, familial subarachnoid hemorrhage, earlier atherosclerotic disease, treatment volume, endovascular modality (for endovascular treatment) or extra aneurysm configuration factors (for microneurosurgical treatment; branching artery from aneurysm neck or unfavorable dome-to-neck ratio), and age (acronym: SAFETEA). For endovascular treatment (n=752), the c-statistic was 0.72 (95%CI:0.67-0.77) and the absolute complication risk ranged from 3.2% (95%CI:1.6%-14.9%;≤1 point) to 33.1% (95%CI:25.4%-41.5%;≥6 points). For microneurosurgical treatment (n=530), the c-statistic was 0.72 (95%CI:0.67-0.77) and the complication risk ranged from 4.9% (95%CI:1.5%-14.9%;≤1 point) to 49.9% (95%CI:39.4%-60.6%;≥6 points). CONCLUSIONS: The SAFETEA risk scores for endovascular and microneurosurgical treatment are based on seven easily retrievable risk factors to predict the absolute risk of procedural complications in patients with unruptured intracranial aneurysms. The scores need external validation before the predicted risks can be properly used to support decision making in clinical practice.

A Mendelian randomization-based exploration of red blood cell distribution width and mean corpuscular volume with risk of hemorrhagic strokes.

Red blood cell distribution width (RCDW) and mean corpuscular volume (MCV) are associated with different risk factors for hemorrhagic stroke. However, whether RCDW and MCV are causally related to hemorrhagic stroke remains poorly understood. Therefore, we explored the causality between RCDW/MCV and nontraumatic hemorrhagic strokes using Mendelian randomization (MR) methods. We extracted exposure and outcome summary statistics from the UK Biobank and FinnGen. We evaluated the causality of RCDW/MCV on four outcomes (subarachnoid hemorrhage [SAH], intracerebral hemorrhage [ICH], nontraumatic intracranial hemorrhage [nITH], and a combination of SAH, cerebral aneurysm, and aneurysm operations) using univariable MR (UMR) and multivariable MR (MVMR). We further performed colocalization and mediation analyses. UMR and MVMR revealed that higher genetically predicted MCV is protective of ICH (UMR: odds ratio [OR] = 0.89 [0.8-0.99], p = 0.036; MVMR: OR = 0.87 [0.78-0.98], p = 0.021) and nITH (UMR: OR = 0.89 [0.82-0.97], p = 0.005; MVMR: OR = 0.88 [0.8-0.96], p = 0.004). There were no strong causal associations between RCDW/MCV and any other outcome. Colocalization analysis revealed a shared causal variant between MCV and ICH; it was not reported to be associated with ICH. Proportion mediated via diastolic blood pressure was 3.1% (0.1%,14.3%) in ICH and 3.4% (0.2%,15.8%) in nITH. The study constitutes the first MR analysis on whether genetically elevated RCDW and MCV affect the risk of hemorrhagic strokes. UMR, MVMR, and mediation analysis revealed that MCV is a protective factor for ICH and nITH, which may inform new insights into the treatments for hemorrhagic strokes.

Machine learning algorithms identify demographics, dietary features, and blood biomarkers associated with stroke records.

OBJECTIVE: We conducted a comprehensive evaluation of features associated with stroke records. METHODS: We screened the dietary nutrients, blood biomarkers, and clinical information from the National Health and Nutrition Examination Survey (NHANES) 2015-16 database to assess a self-reported history of all strokes (136 strokes, n = 4381). We computed feature importance, built machine learning (ML) models, developed a nomogram, and validated the nomogram on NHANES 2007-08, 2017-18, and the baseline UK Biobank. We calculated the odds ratios with/without adjusting sampling weights (OR/ORw). RESULTS: The clinical features have the best predictive power compared to dietary nutrients and blood biomarkers, with 22.8% increased average area under the receiver operating characteristic curves (AUROC) in ML models. We further modeled with ten most important clinical features without compromising the predictive performance. The key features positively associated with stroke include age, cigarette smoking, tobacco smoking, Caucasian or African American race, hypertension, diabetes mellitus, asthma history; the negatively associated feature is the family income. The nomogram based on these key features achieved good performances (AUROC between 0.753 and 0.822) on the test set, the NHANES 2007-08, 2017-18, and the UK Biobank. Key features from the nomogram model include age (OR = 1.05, ORw = 1.06), Caucasian/African American (OR = 2.68, ORw = 2.67), diabetes mellitus (OR = 2.30, ORw = 1.99), asthma (OR = 2.10, ORw = 2.41), hypertension (OR = 1.86, ORw = 2.10), and income (OR = 0.83, ORw = 0.81). CONCLUSIONS: We identified clinical key features and built predictive models for assessing stroke records with high performance. A nomogram consisting of questionnaire-based variables would help identify stroke survivors and evaluate the potential risk of stroke.

D2-Net: Dual Disentanglement Network for Brain Tumor Segmentation With Missing Modalities.

Multi-modal Magnetic Resonance Imaging (MRI) can provide complementary information for automatic brain tumor segmentation, which is crucial for diagnosis and prognosis. While missing modality data is common in clinical practice and it can result in the collapse of most previous methods relying on complete modality data. Current state-of-the-art approaches cope with the situations of missing modalities by fusing multi-modal images and features to learn shared representations of tumor regions, which often ignore explicitly capturing the correlations among modalities and tumor regions. Inspired by the fact that modality information plays distinct roles to segment different tumor regions, we aim to explicitly exploit the correlations among various modality-specific information and tumor-specific knowledge for segmentation. To this end, we propose a Dual Disentanglement Network (D2-Net) for brain tumor segmentation with missing modalities, which consists of a modality disentanglement stage (MD-Stage) and a tumor-region disentanglement stage (TD-Stage). In the MD-Stage, a spatial-frequency joint modality contrastive learning scheme is designed to directly decouple the modality-specific information from MRI data. To decompose tumor-specific representations and extract discriminative holistic features, we propose an affinity-guided dense tumor-region knowledge distillation mechanism in the TD-Stage through aligning the features of a disentangled binary teacher network with a holistic student network. By explicitly discovering relations among modalities and tumor regions, our model can learn sufficient information for segmentation even if some modalities are missing. Extensive experiments on the public BraTS-2018 database demonstrate the superiority of our framework over state-of-the-art methods in missing modalities situations. Codes are available at https://github.com/CityU-AIM-Group/D2Net.

Gods and monsters: Greek mythology and Christian references in the neurosurgical lexicon.

BACKGROUND: Myths and religion are belief systems centered around supernatural entities that attempt to explain the observed world and are of high importance to certain communities. The former is a collection of stories that belong to a cultural tradition and the latter are organized faiths that determine codes of ethics, rituals and philosophy. Deities or monstrous creatures in particular act as archetypes instructing an individual's conduct. References to them in Greek mythology and Christianity are frequently manifested in the modern neurosurgical vernacular. METHODS: A review of the medical literature was performed using the PubMed and MEDLINE bibliographic databases. Publications from 1875 to 2021 related to neurosurgery or neuroanatomy with the medical subject headings (MeSH) terms mythology, religion, Christianity and Catholicism were reviewed. References pertaining to supernatural beings were classified to either a deity or a monstrosity according to their conventional cultural context. RESULTS: Twelve narratives associated with neurosurgery were identified, nine relating to Greek mythology and three associated with the Christian-Catholic faith. Eight accounts concerned deities and the remaining with monstrous creatures. CONCLUSION: This article explores the etymology of commonly utilized terms in daily neurosurgical practice in the context of mythology and religion. They reveal the ingenuity and creativity of early pioneers who strived to understand the brain.

Instance importance-Aware graph convolutional network for 3D medical diagnosis.

Automatic diagnosis of 3D medical data is a significant goal of intelligent healthcare. By exploiting the abundant pathological information of 3D data, human experts and algorithms can provide accurate predictions for patients. Considering the high cost of collecting exhaustive annotations for 3D data, a sustainable alternative is to develop diagnosis algorithms with merely patient-level labels. Motivated by the fact that 2D slices of 3D data hold explicit diagnostic efficacy, we propose the Instance Importance-aware Graph Convolutional Network (I2GCN) under the multi-instance learning (MIL). Specifically, we first calculate the instance importance of each slice towards diagnosis using a preliminary MIL classifier, which is further utilized to promote the refined diagnosis branch. In the refined diagnosis branch, we devise the Instance Importance-aware Graph Convolutional Layer (I2GCLayer) to exploit complementary features in both importance-based and feature-based topologies. Moreover, to alleviate the deficient supervision of 3D dataset, we propose the importance-based Sub-Graph Augmentation (SGA) to effectively regularize the framework training. Extensive experiments confirm the effectiveness of our method with different organs and modals on the CC-CCII and PROSTATEx datasets, which outperforms state-of-the-art methods by a large margin. The source code is available at https://github.com/CityU-AIM-Group/I2GCN.

Reducing meningo-cerebral adhesions by implanting an interpositional subdural polyesterurethane graft after high-grade glioma resection.

BACKGROUND: Meningo-cerebral adhesions are frequently encountered during recurrent high-grade glioma resections. Adhesiolysis not only lengthens operation times, but can also induce focal cortical tissue injury that could affect overall survival. METHODS: Immediately after the primary resection of a high-grade glioma, a polyesterurethane interpositional graft was implanted in the subdural space covering the entire exposed cortex as well as beneath the dural suture line. No postoperative complications were documented. All patients received adjuvant radiotherapy. Upon repeat resection for focal tumor recurrence, the graft was shown to effectively reduce meningo-cerebral adhesion development. CONCLUSION: The implantation of a synthetic subdural graft is a safe and effective method for preventing meningo-cerebral adhesions.

A Morphometric Analysis of Commonly Used Craniometric Approaches for Freehand Ventriculoperitoneal Shunting.

BACKGROUND: Ventricular catheter tip position is a predictor for ventriculoperitoneal shunt survival. Cannulation is often performed freehand, but there is limited consensus on the best craniometric approach. OBJECTIVE: To determine the accuracy of localizing craniometric entry sites and to identify which is associated with optimal catheter placement. METHODS: This is a retrospective analysis of adult patients who underwent ventriculoperitoneal shunting. The approaches were categorized as Kocher's, Keen's, Frazier's and Dandy's points as well as the parieto-occipital point. An accurately sited burr hole was within 10 mm from standard descriptions. Optimal catheter tip position was defined as within the ipsilateral frontal horn. RESULTS: A total of 110 patients were reviewed, and 58% (65/110) of burr holes were accurately sited. Keen's point was the most correctly identified (65%, 11/17), followed by Kocher's point (65%, 37/57) and Frazier's point (60%, 3/5). Predictors for accurate localization were Keen's point (odds ratio 0.3; 95% CI: 01-0.9) and right-sided access (odds ratio 0.4; 95% CI: 0.1-0.9). Sixty-three percent (69/110) of catheters were optimally placed with Keen's point (adjusted odds ratio 0.04; 95% CI: 0.01-0.67), being the only independent factor. Thirteen patients (12%) required shunt revision at a mean duration of 10 ± 25 mo. Suboptimal catheter tip position was the only independent determinant for revision (adjusted odds ratio 0.11; 95% CI: 0.01-0.98). CONCLUSION: This is the first study to compare the accuracy of freehand ventricular cannulation of standard craniometric entry sites for adult patients. Keen's point was the most accurately sited and was a predictor for optimal catheter position. Catheter tip location, not the entry site, predicted shunt survival.

Diagnostic radiation-induced regression of a metastatic primary intracranial germinoma: a case report.

Pineal region germinomas are sensitive to radiotherapy. Standard neurosurgical management involves obtaining a tissue biopsy and to relieve the often accompanying obstructive hydrocephalus. We present a patient with a suspected hyper-radiosensitive metastatic primary intracranial germinoma where computed tomography scanning resulted in tumor regression before radiotherapy could be administered.

Dose-Response Relationship and Threshold Drug Dosage Identification for a Novel Hybrid Mechanical-Thrombolytic System with an Ultra-Low Dose Patch.

INTRODUCTION: Ischemic stroke treatment has advanced in the last two decades and intravenous thrombolysis is now considered the standard of care for selected patients. Recanalization can also be achieved by mechanical endovascular treatment for patients with large vessel occlusions. Complicating treatment-related symptomatic intracerebral hemorrhage and prolonged needle-to-recanalization times have been identified as major determinants of poor three-month functional outcomes. A hybrid mechanical-thrombolytic system with a patch imbued with an ultra-low dose of thrombolytic agents loaded onto a stent-retriever has been developed. METHODS: In this study, the in situ dose-response relationship of the thrombolytic patch imbued with up to 1000 IU of urokinase plasminogen activator (uPA) was quantified using Raman spectroscopy. RESULTS: Thrombi of up to 400 µm thickness dissolved within 15 min when patches imbued with < 1% of the conventional thrombolysis therapy dosage were applied. The results demonstrated that low-dose thrombolytic patches can dissolve normal clots compressed in the blood vessel in a short time. 500 IU is the threshold uPA dosage in the thrombolytic patch that most effectively dissolves the clots. CONCLUSION: This study suggests that a novel endovascular stent-retriever loaded with an ultra-low drug dose fibrinolytic patch may be a suitable treatment for patients who are ineligible for conventional thrombolytic therapy.

"When the Benign Bleed" Vestibular Schwannomas with Clinically Significant Intratumoral Hemorrhage: A Case Series and Review of the Literature.

Vestibular schwannomas (VSs) are slow-growing benign neoplasms commonly located at the cerebellopontine angle. Although clinically significant hemorrhagic VSs are rarely encountered with only 75 patients previously reported, they could be life threatening. We discuss the presentation and outcomes of three patients with hemorrhagic VS as well as review the literature for this phenomenon. Consecutive adult patients with a histologically proven diagnosis of VS over a 9-year period were retrospectively reviewed. Fifty adult patients were identified with three (6%) having clinically significant intratumoral hemorrhage. This was defined as patients having acute to subacute symptoms with frank radiological evidence of hemorrhage. The mean age of diagnosis was 62 ± 9 years and the male-to female ratio was 2:1. The mean duration of symptoms, namely headache, vertigo, and sensorineural hearing impairment, was 26 ± 4 days with one patient presenting with acute coma. Retrosigmoid craniotomy for tumor resection was performed for all patients. Histopathological examination revealed extensive areas of microhemorrhage with considerable macrophage infiltration. All three patients were discharged with no additional neurological deficit and good functional performance. Clinically significant hemorrhagic VSs are rare, and patients may present with acute to subacute (i.e., within a month) symptoms of hearing loss headache, facial, or trigeminal nerve palsy. Macrophage infiltration is frequently encountered in tumor specimens and reflects the pivotal role of chronic inflammation in their pathophysiology. Surgical resection can lead to good outcomes with timely intervention.

The protean manifestations of central nervous system IgG4-related hypertrophic pachymeningitis: a report of two cases.

BACKGROUND: IgG4-related hypertrophic pachymeningitis is a relative newly recognized and rare manifestation of IgG4-related disease, an immune-mediated fibroinflammatory tumefactive disorder. Fewer than 80 patients have been reported in the literature, and it can mimic common neurosurgical conditions. We describe the clinical presentation of two patients that were initially considered to have a subdural collection, tuberculous meningitis, and a cervical spinal meningioma, but were eventually diagnosed with this disease. CASE PRESENTATION: Two ethnic Chinese men, 86 and 62 years old, experienced a 4-week history of headache. Both patients had a history of autoimmune disease, namely glomerulonephritis and Grave's disease, respectively. Magnetic resonance brain imaging revealed diffuse dural thickening with the latter patient exhibiting homogeneous and intense gadolinium-contrast enhancement. Since the 86-year-old patient also had progressive bilateral visual loss, giant cell arteritis was suspected and a 2-week course of glucocorticoid therapy was prescribed, but his symptoms failed to improve. The 62-year-old patient also had accompanying low-grade fever and was treated empirically as having tuberculous meningitis although there were no confirmatory microbiological findings. This patient further developed right hemiparesis, and additional imaging revealed a C4/5 intradural-extramedullary contrast-enhancing lesion resembling a meningioma causing cord compression. Both patients underwent neurosurgical intervention with the former undergoing a dural biopsy and the latter having the cervical lesion resected. The final diagnosis was IgG4-related hypertrophic pachymeningitis with the hallmark histological features of lymphoplasmacytic infiltration of IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. In addition, their serum IgG4 levels were elevated (i.e., > 135 mg/dL). Both patients received at least 6 months of glucocorticoid therapy while the latter also had azathioprine. Their symptoms improved significantly and recurrent lesions were not detected on follow-up imaging. CONCLUSIONS: A high index of suspicion for this condition is suggested when a male patient with a history of autoimmune disease and compatible radiological findings, experiences subacute headache that is disproportionate to the degree of dural involvement. Neurosurgeons should consider early meningeal biopsy to establish a definitive histological diagnosis in order for early effective immunosuppressive treatment to be initiated and to avoid unnecessary morbidity.