Non-shunt Management of Communicating Hydrocephalus in an Immunocompetent Host With Disseminated Central Nervous System Coccidioidomycosis.

Disseminated coccidioidomycosis is associated with significant morbidity and mortality. Involvement of the meninges is often fatal if untreated, typically requiring lifelong antifungal therapy and neurosurgical intervention. We present the case of a young male without any known immunocompromising conditions who opted exclusively for medical management of newly diagnosed coccidioidomycosis meningitis with communicating hydrocephalus and discuss the controversy associated with this approach. This case highlights the importance of shared decision-making between patient and clinician, even if the plan diverges from available guidelines. Furthermore, we discuss clinical considerations in approaching the close outpatient monitoring of patients with central nervous system coccidioidomycosis with hydrocephalus.

Is there a role in the central nervous system development for using corticosteroids to treat meningomyelocele and hydrocephalus?

INTRODUCTION: Myelomeningocele (MMC) is the most frequent neural tube defect and is frequently associated (around 80% of cases) with hydrocephalus (HC). Both diseases can have severe clinical consequences, insomuch as they require surgical treatment whose complications are not negligible, either when performed in utero or after birth. Therefore, clinical therapies that could have an impact on the incidence and progression of MMC and HC would be certainly valuable; however, this is not the current picture, and there are no effective pharmacological treatments for such patients to this day. AIM AND METHODS: Therefore, knowing that an inflammatory process comes associated with these disorders, mostly due to nervous tissue distension, the present article aimed at reviewing the role of corticosteroids in reducing inflammation and thus improving the outcome of patients with HC and MMC, considering the well-established anti-inflammatory effects of CS. RESULTS: The systematic review performed herein has found varying results regarding the role of steroids (even though a positive trend was observed) on the treatment and prevention of hydrocephalus, whereas for MMC. CONCLUSION: There are many reports demonstrating beneficial effects of CS therapy, from a clinical and histopathological point of view.

Microglia replacement by bone marrow transplantation (Mr BMT) in the central nervous system of adult mice.

Microglia are important immune cells in the central nervous system (CNS). Mutations in microglia may cause CNS disorders. Replacement of dysfunctional microglia with allogeneic wild-type microglia can correct the gene deficiency, thus treating the neurogenic diseases. However, traditional approaches cannot efficiently replace microglia at the adulthood. Here, we introduce a potentially clinical-feasible strategy named microglia replacement by bone marrow transplantation that achieves efficient microglia replacement at the whole CNS scale, including the brain, spinal cord, and retina in adult mice. For complete details on the use and execution of this protocol, please refer to Xu et al. (2020). The original abbreviation of this microglia replacement strategy is mrBMT. We hereby change the name to Mr BMT.

Adaptive self-healing electronic epineurium for chronic bidirectional neural interfaces.

Realizing a clinical-grade electronic medicine for peripheral nerve disorders is challenging owing to the lack of rational material design that mimics the dynamic mechanical nature of peripheral nerves. Electronic medicine should be soft and stretchable, to feasibly allow autonomous mechanical nerve adaptation. Herein, we report a new type of neural interface platform, an adaptive self-healing electronic epineurium (A-SEE), which can form compressive stress-free and strain-insensitive electronics-nerve interfaces and enable facile biofluid-resistant self-locking owing to dynamic stress relaxation and water-proof self-bonding properties of intrinsically stretchable and self-healable insulating/conducting materials, respectively. Specifically, the A-SEE does not need to be sutured or glued when implanted, thereby significantly reducing complexity and the operation time of microneurosurgery. In addition, the autonomous mechanical adaptability of the A-SEE to peripheral nerves can significantly reduce the mechanical mismatch at electronics-nerve interfaces, which minimizes nerve compression-induced immune responses and device failure. Though a small amount of Ag leaked from the A-SEE is observed in vivo (17.03 ppm after 32 weeks of implantation), we successfully achieved a bidirectional neural signal recording and stimulation in a rat sciatic nerve model for 14 weeks. In view of our materials strategy and in vivo feasibility, the mechanically adaptive self-healing neural interface would be considered a new implantable platform for a wide range application of electronic medicine for neurological disorders in the human nervous system.

Efficient Strategies for Microglia Replacement in the Central Nervous System.

Microglia are important immune cells in the central nervous system (CNS). Dysfunctions of gene-deficient microglia contribute to the development and progression of multiple CNS diseases. Microglia replacement by nonself cells has been proposed to treat microglia-associated disorders. However, some attempts have failed due to low replacement efficiency, such as with the traditional bone marrow transplantation approach. In this study, we develop three efficient strategies for microglia replacement: microglia replacement by bone marrow transplantation (mrBMT), microglia replacement by peripheral blood (mrPB), and microglia replacement by microglia transplantation (mrMT). mrBMT and mrPB allow microglia-like cells to efficiently replace resident microglia in the whole CNS. On the other hand, mrMT achieves microglia replacement in brain regions of interest. In summary, the present study offers effective tactics for microglia replacement with diverse application scenarios, which potentially opens up a window on treating microglia-associated CNS disorders.

Intracranial Infections in Neurological Surgery: The Changes of Circular RNA Expression and Their Possible Function Mechanism.

METHODS: circRNA expression was analysed in six cerebrospinal fluid (CSF) samples from three patients of the infectious and noninfectious phases using an Arraystar Human circRNA Array. Differentially altered circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in the 66 CSF samples of 33 patients of the infectious and noninfectious phases. t-test was used for statistical analysis. A bioinformatics analysis was employed to investigate the function mechanism of the circRNAs. RESULTS: Firstly, 142 circRNAs were found significantly different in 6 CSF samples of the infection and noninfection phases of 3 patients. Fourteen circRNAs with the top largest fold changes were chosen from the 142 circRNAs for PCR validation in the same 6 CSF samples of 3 patients. Three circRNAs were selected to be validated in 60 CSF samples of 30 patients using the PCR test. In infection CSF, an upregulated hsa_circRNA_402632 and downregulated hsa_circRNA_008636 and hsa_circRNA_405481 were confirmed by PCR test. A bioinformatics analysis was used to investigate the function mechanism of the 3 circRNAs. hsa_circRNA_402632 is enriched in the insulin resistance pathway, the FoxO and AMPK signaling pathways are the most important pathways for hsa_circRNA_008636 gene expression, and hsa_circRNA_405481 is enriched in the endometrial cancer signaling pathway, Fc epsilon RI signaling pathway, and TGF-beta signaling pathway. CONCLUSIONS: hsa_circRNA_402632, hsa_circRNA_008636, and hsa_circRNA_405481 may be potential diagnostic markers for central nervous system infection after neurological surgery.

Case of Calcifying Pseudoneoplasms of the Neuraxis Coexisting with Interhemispheric Lipoma and Agenesis of the Corpus Callosum: Involvement of Infiltrating Macrophages.

BACKGROUND: Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare clinical entity. We report an unusual case of intraparenchymal bifrontal CAPNON coexisting with interhemispheric lipoma and agenesis of the corpus callosum. CASE DESCRIPTION: A 64-year-old woman presented with slight weakness of her left leg. Computed tomography and magnetic resonance imaging showed massive nodular intraparenchymal calcifications at both sides of the interhemispheric lipoma associated with partial agenesis of the corpus callosum. Enhancement was observed at the periphery and within the calcification. Massive perifocal edema was also demonstrated. The enhanced lesion with calcification was partially resected. Histologic analysis of the resected specimen disclosed nodular calcification with fibro-osseous components and histiocytic reaction, consistent with CAPNON. A high ratio of M2 macrophages was observed among the infiltrating macrophages. 11C-methionine positron emission tomography demonstrated high uptake of the tracer at the lesion corresponding to the calcified lesion on computed tomography. Postoperatively, massive perifocal edema was decreased and maintained without progression for a year. CONCLUSIONS: The high M2 macrophage activity verified by histopathologic analysis suggests that CAPNON is not a silent but a more active, tumefactive disease involving the immune response. This hypothesis may be supported by the high uptake of 11C-methionine positron emission tomography.

Dysfunction of the blood-brain barrier in postoperative delirium patients, referring to the axonal damage biomarker phosphorylated neurofilament heavy subunit.

BACKGROUND: Delirium is the most common postoperative complication of the central nervous system (CNS) that can trigger long-term cognitive impairment. Its underlying mechanism is not fully understood, but the dysfunction of the blood-brain barrier (BBB) has been implicated. The serum levels of the axonal damage biomarker, phosphorylated neurofilament heavy subunit (pNF-H) increase in moderate to severe delirium patients, indicating that postoperative delirium can induce irreversible CNS damage. Here, we investigated the relationship among postoperative delirium, CNS damage and BBB dysfunction, using pNF-H as reference. METHODS: Blood samples were collected from 117 patients within 3 postoperative days. These patients were clinically diagnosed with postoperative delirium using the Confusion Assessment Method for the Intensive Care Unit. We measured intercellular adhesion molecule-1, platelet and endothelial cell adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and P-selectin as biomarkers for BBB disruption, pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6), and pNF-H. We conducted logistic regression analysis including all participants to identify independent biomarkers contributing to serum pNF-H detection. Next, by multiple regression analysis with a stepwise method we sought to determine which biomarkers influence serum pNF-H levels, in pNF-H positive patients. RESULTS: Of the 117 subjects, 41 were clinically diagnosed with postoperative delirium, and 30 were positive for serum pNF-H. Sensitivity and specificity of serum pNF-H detection in the patients with postoperative delirium were 56% and 90%, respectively. P-selectin was the only independent variable to associate with pNF-H detection (P < 0.0001) in all 117 patients. In pNF-H positive patients, only PECAM-1 was associated with serum pNF-H levels (P = 0.02). CONCLUSIONS: Serum pNF-H could be an objective delirium biomarker, superior to conventional tools in clinical settings. In reference to pNF-H, P-selectin may be involved in the development of delirium-related CNS damage and PECAM-1 may contribute to the progression of delirium- related CNS damage.

Injection and Infusion of Compounds to the Central Nervous System.

The present protocol describes in detail the steps necessary for executing two highly versatile and minimally invasive surgical approaches for localized delivery of compounds to the central nervous system. The procedures have been designed for use on laboratory mice but can also be tailored for experimentations involving other small rodent models. Following the instructions outlined below, treatments can either be administered through single injections or infused over a longer period of time, at locations identified through stereotaxic coordinates, which ensure efficient targeting of the brain region of interest, as well as increased reproducibility between surgeries. Although the surgical interventions are well tolerated by laboratory animals, it is recommended to closely monitor the mice postoperatively for a few days, and take the necessary measures to prevent stress and discomfort.

[The application of hybrid operation suite in the management of cerebral and spinal vascular diseases and intracranial hypervascular tumors].

Objective: To evaluate the effect of hybrid operation suite in the treatment of cerebral and spinal vascular diseases and intracranial hypervascular tumors. Methods: A retrospective study was conducted on 132 patients with various cerebral and spinal vascular diseases and intracranial hypervascular tumors who were treated by hybrid surgery at Department of Neurosurgery, Huashan Hospital from October 2016 to December 2017.There were 70 male and 62 female patients with a mean age of 48.33 years (range: 14-78 years), including 64 cases of intracranial aneurysm (41 complicated aneurysm cases), 28 cases of brain arteriovenous malformation (BAVM), 12 cases of hypervascular tumor, 12 cases of dural arteriovenous fistula (DAVF), 6 cases of carotid artery stenosis, 5 cases of Moyamoya disease, 3 cases of intracranial aneurysm or BAVM combined with tumor, 1 case of scalp arteriovenous fistula and 1 case of critical brain trauma in which a foreign metal stick approached the basal vascular circuit.Abnormalities were found in 16 cases in intraoperative angiography. The clinical data of all patients was collected as a perspective cohort. The success rate of hybrid surgery, intra-operative and post-operative complications, morbidity, mortality, rate of infection, the length of hospital stay were all analyzed to illustrate the effect of hybrid operation mode to traditional surgical pattern. Results: For 64 cases with intracranial aneurysms, the immediate complete occlusion rate was 90.5%, with a mortality of 4.7% and a morbidity of 14.0%. For 28 cases of BAVM and 12 cases of DAVF, all patients achieved total obliteration and favorable social independent outcomes after hybrid surgery, with no complication.For 6 cases of carotid artery stenosis and 5 cases of Moyamoya, intra-operative confirmed good cerebral reperfusion without any new post-operative neurologic deficits. After tumor vessels embolization, 4 out of 12 cases of hypervascular tumor needed intra-operative blood transfusion, and all patients achieved total tumor resection in a single stage. Only one patient with medulla oblongata hemangioblastoma died 6 months after operation due to respiratory deficit related pneumonia. Compared to traditional surgeries, the hybrid operation pattern did not significantly increase the total infection rate, central nervous system infection rate, hospital stay days and post-operative hospital stay days (all P>0.05) while the in-patient cost increased mildly (119 332 yuan vs.98 215 yuan, t=2.38, P=0.02). Conclusions: The operations of complex cerebral and spinal vascular diseases and intracranial hypervascular tumors can be performed in hybrid operation suite safely.This surgical mode can ensure the quality of operation and promote the development of innovative and complicated surgical procedures.

Accuracy of Intraoperative Examination in Central Nervous System Lesions: A Study of 133 Cases.

OBJECTIVE: Intraoperative examination is a highly valuable tool for the evaluation of central nervous system (CNS) lesions, helping the neurosurgeon to determine the best surgical management. This study aimed to evaluate the accuracy and to analyze the diagnostic disagreements and pitfalls of the intraoperative examinations through correlation with the final histopathological diagnosis in CNS lesions. STUDY DESIGN: Retrospective analysis of intraoperative examination of CNS lesions and their final diagnosis obtained during 16 consecutive years. All diagnoses were reviewed and classified according to World Health Organization (WHO) grading for CNS tumors. Squash was performed in 119 cases, while frozen section and both methods were done in 7 cases each. RESULTS: Among the 133 intraoperative examinations considered, 114 (85.7%) presented concordance and 19 (14.3%) diagnostic disagreement when compared with subsequent histopathological examinations. The sensitivity and specificity for the detection of neoplasia in intraoperative examination was 98 and 94%, respectively. The positive and negative predictive values were 99 and 88%, respectively. The accuracy for neoplastic and nonneoplastic disease was 85.7%. Disagreements were more frequent among low-grade (WHO grades I and II) neoplasms and nonmalignant cases. CONCLUSIONS: Our results showed good accuracy of the intraoperative assessments for diagnosis of CNS lesions, particularly in high-grade (grades III and IV) lesions and metastatic neoplasms.

Updating superficial siderosis of the central nervous system: bleeding of a dorsal osteophyte into the subarachnoid space from a perforating artery.

Superficial siderosis of the central nervous system (SSCNS) is an uncommon and often unrecognized disorder that results from recurrent and persistent bleeding into the subarachnoid space. Currently, there is no effective treatment for SSCNS. The identification and surgical resolution of the cause of bleeding remains the most reliable method of treatment, but the cause of bleeding is often not apparent. The identified sources of recurrent bleeding have typically included neoplasms, vascular malformations, brachial plexus or nerve root injury or avulsion, and previous head and spinal surgery. An association between recurrent bleeding in the CNS and dural abnormalities in the spine has recently been suggested. Dural tears have been identified in relation to a protruding disc or osteophyte. Also in these patients, the exact mechanism of bleeding remains unknown because of a lack of objective surgical data, even in patients who undergo neurosurgical procedures.The present case concerns a 48-year-old man who presented with longstanding symptoms of mild hearing loss and mild gait ataxia. A diagnosis of SSCNS was made in light of the patient's history and the findings on physical examination, imaging, and laboratory testing. MRI and CT detected a small calcific osteophyte in the anterior epidural space of T8-9. The patient underwent surgical removal of the bone spur and dural tear repair. During the surgery, the authors detected a perforating artery, which was on the osteophyte, that was bleeding into the subarachnoid space. This case shows a possible mechanism of chronic bleeding from an osteophyte into the subarachnoid space. In the literature currently available, a perforating artery on an osteophyte bleeding into the subarachnoid space has never been described in SSCNS.

Surgical approach for suprasellar hemangioblastomas preserving the pituitary stalk: Review of the literature and report of a further case.

Hemangioblastomas (HBLs) are challenging vascular tumours with rare suprasellar location Surgery is recommended in patients with visual impairment, endocrine disorders or hydrocephalus. Surgical removal of pituitary stalk HBLs is challenging due to their location and high vascularity. Our narrative review was guided by the question: "what is the more suitable surgical approach to excise a suprasellar HBL?". Pertinent English literature was scrutinized from database inception to October 2016. Eighteen articles matched our selection criteria. Among the surgically treated patients, 4 were treated through a trans-sphenoidal (TS) approach, 13 through a transcranial approach (2 of them after TS failure). Five other cases were treated with radiotherapy (adjuvant in 3 cases) and 9 patients were managed with simple observation and/or medical treatment. We add a case of complete suprasellar HBL resection through an orbito-zygomatic (OZ) craniotomy with extradural anterior clinoidectomy (EAC). To achieve satisfactory oncologic results with acceptable morbidity for symptomatic suprasellar HBLs, complete tumour removal with pituitary stalk sparing should be attempted through an OZ craniotomy with EAC that provides adequate exposure of the tumour, its vascular supply and the adjacent neural structures.

[A Rare Case of Cerebellar Hemangioblastoma Causing Taste Disorder].

Taste(gustation)is one of the five senses, and comprises the types: sweet, bitter, salty, sour, and umami. Taste disorders, such as dysgeusia and parageusia, are classified into 2 types: those with peripheral origin and those with central origin. The peripheral origin-type taste disorder is caused by zinc deficiency, mouth dryness, a side effect of radiotherapy or complication of systemic diseases such as, diabetes, hepatopathy, and nephropathy. The central origin-type taste disorder is reported to be caused due to demyelinating disease, pontine hemorrhage, pontine infarction, and thalamic infarction; it is very rarely caused by a brain tumor. We surgically treated a 69-year-old man with cerebellar hemangioblastoma who had developed taste disorder. The tumor compressed the solitary nucleus, which includes the taste tract in the central nervous system. On removal of the tumor, the taste disorder gradually improved.

Characteristics of Rosai-Dorfman Disease Primarily Involved in the Central Nervous System: 3 Case Reports and Review of Literature.

OBJECTIVE: This study aimed to summarize the clinical characteristics of Rosai-Dorfman disease primarily involving the central nervous system and to explore diagnosis and treatment. METHODS: We analyzed the clinical, imaging, and pathologic characteristics; treatment; and prognosis in 3 cases of Rosai-Dorfman disease primarily involving the central nervous system. We also performed a literature review. RESULTS: The largest of multiple intracranial lesions was totally resected, and steroid administration and radiotherapy were performed in phases for the remaining lesions. During the 1-year follow-up period, the excised lesion did not recur, and no obvious variations were observed in the other lesions. Subtotal resection was performed of the largest of another group of multiple intracranial lesions, and the residual did not show any obvious variations during the 1-year follow-up period. The isolated lesion was totally resected and did not recur during a 2-year follow-up period. CONCLUSIONS: Rosai-Dorfman disease with multiple lesions primarily involving the central nervous system is rare. Imaging characteristics are similar to meningiomas, and the pathological features include lymphocytes and plasma cells reaching tissue cells with large volume and abundant cytoplasm. Surgery is the preferred treatment, as the effects of steroid administration and radiotherapy are not apparent.

Neurobiochemical changes in the vicinity of a nanostructured neural implant.

Neural interface technologies including recording and stimulation electrodes are currently in the early phase of clinical trials aiming to help patients with spinal cord injuries, degenerative disorders, strokes interrupting descending motor pathways, or limb amputations. Their lifetime is of key importance; however, it is limited by the foreign body response of the tissue causing the loss of neurons and a reactive astrogliosis around the implant surface. Improving the biocompatibility of implant surfaces, especially promoting neuronal attachment and regeneration is therefore essential. In our work, bioactive properties of implanted black polySi nanostructured surfaces (520-800 nm long nanopillars with a diameter of 150-200 nm) were investigated and compared to microstructured Si surfaces in eight-week-long in vivo experiments. Glial encapsulation and local neuronal cell loss were characterised using GFAP and NeuN immunostaining respectively, followed by systematic image analysis. Regarding the severity of gliosis, no significant difference was observed in the vicinity of the different implant surfaces, however, the number of surviving neurons close to the nanostructured surface was higher than that of the microstructured ones. Our results imply that the functionality of implanted microelectrodes covered by Si nanopillars may lead to improved long-term recordings.

Management of granulomatous cerebral aspergillosis in immunocompetent adult patients: a review.

Cerebral aspergillosis, is an infrequent, opportunistic infection of the central nervous system that accounts for 5-10% of all intracranial fungal pathology. It is uncommon in immunocompetent patients and has a significant disease burden, with high morbidity and mortality, even with appropriate treatment. Basic principles of abscess management should be employed, including aspiration and targeted anti-fungal therapy for 12-18 months. However, reported outcomes with a purely minimally invasive approach are poor and there should be a low threshold for surgical excision, especially in resource poor settings and in patients with deteriorating neurology harbouring sizeable masses. Evidence favouring gross total excision over subtotal resection is lacking, however. It is notable that these recommendations are largely based on retrospective case series and isolated case reports. There is a need therefore for international collaboration to evaluate management strategies for immunocompetent patients with cerebral aspergillosis.

High-resolution imaging of the central nervous system: how novel imaging methods combined with navigation strategies will advance patient care.

This narrative review captures a subset of recent advances in imaging of the central nervous system. First, we focus on improvements in the spatial and temporal profile afforded by optical coherence tomography, fluorescence-guided surgery, and Coherent Anti-Stokes Raman Scattering Microscopy. Next, we highlight advances in the generation and uses of imaging-based atlases and discuss how this will be applied to specific clinical situations. To conclude, we discuss how these and other imaging tools will be combined with neuronavigation techniques to guide surgeons in the operating room. Collectively, this work aims to highlight emerging biomedical imaging strategies that hold potential to be a valuable tool for both clinicians and researchers in the years to come.

"Extremely minimally invasive": recent advances in nanotechnology research and future applications in neurosurgery.

The term "nanotechnology" refers to the development of materials and devices that have been designed with specific properties at the nanometer scale (10(-9) m), usually being less than 100 nm in size. Recent advances in nanotechnology have promised to enable visualization and intervention at the subcellular level, and its incorporation to future medical therapeutics is expected to bring new avenues for molecular imaging, targeted drug delivery, and personalized interventions. Although the central nervous system presents unique challenges to the implementation of new therapeutic strategies involving nanotechnology (such as the heterogeneous molecular environment of different CNS regions, the existence of multiple processing centers with different cytoarchitecture, and the presence of the blood-brain barrier), numerous studies have demonstrated that the incorporation of nanotechnology resources into the armamentarium of neurosurgery may lead to breakthrough advances in the near future. In this article, the authors present a critical review on the current 'state-of-the-art' of basic research in nanotechnology with special attention to those issues which present the greatest potential to generate major therapeutic progresses in the neurosurgical field, including nanoelectromechanical systems, nano-scaffolds for neural regeneration, sutureless anastomosis, molecular imaging, targeted drug delivery, and theranostic strategies.