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Poxviridae is a diverse family of double‐stranded DNA viruses, historically significant for diseases like smallpox caused by variola virus (VARV). These viruses exhibit unique cytoplasmic replication strategies, large genomes encoding numerous proteins, and the ability to cause severe cutaneous and systemic diseases. Recent attention has focused on their neurotropic potential, including mechanisms of CNS invasion, immune‐mediated damage, and clinical manifestations such as encephalitis and myelitis. This review synthesises current knowledge on poxvirus neurotropism, highlighting pathophysiological mechanisms and clinical implications. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor that almost exclusively occurs in immunocompromised hosts. Here, we report a 75-year-old Taiwanese woman without definite immune-deficient history presenting with progressive occipital neuralgia, low cranial nerve deficits (CN9-12) and cervical (C1-C5) radiculopathy. Magnetic resonance imaging revealed a 4.5*4.0*6.7 cm infiltrating mass occupying posterior skull base and C1-C2 vertebra and C1-5 epidural extension with bone destruction and vertebral artery (VA) encasement. There was also a synchronous 2.7cm tonsillar tumor. A two-stage operation for cranio-cervical tumor excision and stabilization was performed. Tumor was confirmed directly arising from VA intraoperatively. Pathology reported a spindle cell neoplasm and the diagnosis of EBV-SMT was confirmed by EBER (EBV-encoded small RNA) in situ hybridization. An immune survey and reconstruction should be conducted for patient with EBV-SMT. A near-total resection of tumor may be beneficial for local control, however, the role of surgical resection in treating CNS EBV-SMT remains to be determined. [ABSTRACT FROM AUTHOR]

CNS invasion has been included as an independent criterion for the diagnosis of a high-grade (WHO and CNS grade 2 and 3) meningioma in the 2016 and more recently in the 2021 WHO classification. However, the prognostic role of brain invasion has recently been questioned. Also, surgical treatment for brain invasive meningiomas may pose specific challenges. We conducted a systematic review of the 2016–2022 literature on brain invasive meningiomas in Pubmed, Scopus, Web of Science and the Cochrane Library. The prognostic relevance of brain invasion as a stand-alone criterion is still unclear. Additional and larger studies using robust definitions of histological brain invasion and addressing the issue of sampling errors are clearly warranted. Although the necessity of molecular profiling in meningioma grading, prognostication and decision making in the future is obvious, specific markers for brain invasion are lacking for the time being. Advanced neuroimaging may predict CNS invasion preoperatively. The extent of resection (e.g., the Simpson grading) is an important predictor of tumor recurrence especially in higher grade meningiomas, but also – although likely to a lesser degree – in benign tumors, and therefore also in brain invasive meningiomas with and without other histological features of atypia or malignancy. Hence, surgery for brain invasive meningiomas should follow the principles of maximal but safe resections. There are some data to suggest that safety and functional outcomes in such cases may benefit from the armamentarium of surgical adjuncts commonly used for surgery of eloquent gliomas such as intraoperative monitoring, awake craniotomy, DTI tractography and further advanced intraoperative brain tumor visualization. [ABSTRACT FROM AUTHOR]

CNS invasion has been included as an independent criterion for the diagnosis of a high-grade (WHO and CNS grade 2 and 3) meningioma in the 2016 and more recently in the 2021 WHO classification. However, the prognostic role of brain invasion has recently been questioned. Also, surgical treatment for brain invasive meningiomas may pose specific challenges. We conducted a systematic review of the 2016–2022 literature on brain invasive meningiomas in Pubmed, Scopus, Web of Science and the Cochrane Library. The prognostic relevance of brain invasion as a stand-alone criterion is still unclear. Additional and larger studies using robust definitions of histological brain invasion and addressing the issue of sampling errors are clearly warranted. Although the necessity of molecular profiling in meningioma grading, prognostication and decision making in the future is obvious, specific markers for brain invasion are lacking for the time being. Advanced neuroimaging may predict CNS invasion preoperatively. The extent of resection (e.g., the Simpson grading) is an important predictor of tumor recurrence especially in higher grade meningiomas, but also – although likely to a lesser degree – in benign tumors, and therefore also in brain invasive meningiomas with and without other histological features of atypia or malignancy. Hence, surgery for brain invasive meningiomas should follow the principles of maximal but safe resections. There are some data to suggest that safety and functional outcomes in such cases may benefit from the armamentarium of surgical adjuncts commonly used for surgery of eloquent gliomas such as intraoperative monitoring, awake craniotomy, DTI tractography and further advanced intraoperative brain tumor visualization.

Introduction: and Research Question: Invasive growth of meningiomas into CNS tissue is rare but of prognostic significance. While it has entered the WHO classification as a stand-alone criterion for atypia, its true prognostic impact remains controversial. Retrospective analyses, on which the current evidence is based, show conflicting results. Discordant findings might be explained by different intraoperative sampling methodologies. Material and methods: To assess the applied sampling methods in the light of the novel prognostic impact of CNS invasion, an anonymous survey was designed and distributed via the EANS website and newsletter. The survey was open from June 5th until July 15th, 2022. Results: After exclusion of 13 incomplete responses, 142 (91.6%) datasets were used for statistical analysis. Only 47.2% of participants’ institutions utilize a standardized sampling method, and 54.9% pursue a complete sampling of the area of contact between the meningioma surface and CNS tissue. Most respondents (77.5%) did not change their sampling practice after introduction of the new grading criteria to the WHO classification of 2016. Intraoperative suspicion of CNS invasion changes the sampling for half of the participants (49.3%). Additional sampling of suspicious areas of interest is reported in 53.5%. Dural attachment and adjacent bone are more readily sampled separately if tumor invasion is suspected (72.5% and 74.6%, respectively), compared to meningioma tissue with signs of CNS invasion (59.9%). Discussion and conclusions: Intraoperative sampling methods during meningioma resection vary among neurosurgical departments. There is need for a structured sampling to optimize the diagnostic yield of CNS invasion.

Abstract Epstein‐Barr virus‐associated smooth muscle tumor (EBV‐SMT) is a rare mesenchymal tumor occurred almost exclusively in immunocompromised hosts. This article provides a systematic review of literature under PRISMA guideline on clinical features, treatment modalities, roles of surgical intervention, and outcomes of all 65 reported EBV‐SMTs with central nervous system (CNS) invasion. Over 95% of reported cases were immunocompromised, while human immunodeficiency virus infection and post‐organ transplantation were the most commonly associated underlying causes (near 90%). Despite a heterogeneous follow‐up period, a 1‐year survival rate of 76.0% and 5‐year survival rate of 59.6% may support the indolent and non‐deadly nature of EBV‐SMT even with CNS invasion. Immune survey and reconstruction should be conducted for every patient with CNS EBV‐SMT. Surgical resection is mostly adopted as primary treatment to obtain diagnosis and relieve compressive effect. A total resection of tumor may be beneficial if tumor was symptomatic and had intracranial invasion.

Introduction: Meningiomas are the most common benign intracranial neoplasms. CNS invasion in meningiomas has been integrated into the 2016 WHO classification of CNS tumors as a stand-alone criterion for atypia. Since then, its prognostic impact has been debated based on contradictory results from retrospective analyses. The aim of the study was to elucidate whether histopathological evidence of CNS invasion is associated with increased proliferative potential. Methods: We have conducted a quantified measurement of the proliferation marker Ki67 and analyzed its association with CNS invasion determined by histology together with other established prognostic markers of progression. Routine, immunohistochemical staining for Ki67 were digitalized and automatic quantification was done using Image J software. Results: Overall, 1718 meningiomas were assessed. Histopathological CNS invasion was seen in 108 cases (6.7%). Uni- and multivariate analysis revealed a significantly higher Ki67 proliferation rate in meningiomas with CNS invasion (p < 0.0001 and p = 0.0098, respectively). Conclusions: Meningiomas with histopathological CNS invasion show a higher proliferative activity. [ABSTRACT FROM AUTHOR]

Leptomeningeal myelomatosis (LMM) is a fatal complication that occurs in < 1% of patients with multiple myeloma. Many patients with LMM present with neurologic symptoms referable to cranial neuropathies, while the manifestation of communicating hydrocephalus has been underrecognized. A Japanese man with Bence Jones protein‐κ multiple myeloma developed fever and headache at age 54 years. He then became somnolent and went into a coma. Neuroimaging analyses identified rapidly progressive communicating hydrocephalus due to meningitis. He died 83 days after the onset of headache without any response to treatment at age 55 years. No symptoms or signs associated with cranial nerves were found during the course of illness. Postmortem examination revealed hydrocephalus and diffuse infiltration of myeloma cells into the subarachnoid space of the cerebrum, cerebellum, and brainstem. In addition, the interstitial tissue of the choroid plexuses was filled with myeloma cells. These myeloma cells were positive for CD156 and light chain κ. The Ki‐67 labeling index in myeloma cells of the central nervous system (CNS) was 30–40%. Histopathological examination further revealed many myeloma cells on the surface of the lateral, third and fourth ventricles and at the area postrema of the medulla oblongata. Patients with LMM can develop an aggressive form of communicating hydrocephalus. Given that cerebrospinal fluid, produced by epithelial cells in the choroid plexuses of the ventricles, passes into the subarachnoid space through the third and fourth ventricles, myeloma cells may invade the CNS through the choroid plexuses. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) devastation on the central nervous system (CNS) is ascertained by the present clinical findings and the noticeable signs and symptoms. The CNS involvement of the virus is not trivial; although the brain has highly protective systems, the virus has ways to breach them with a destructive potential. For successful entry of the virus, different possible routes with favorable mechanisms are used. The SARS-CoV-2 invasion induces a mechanism of both the innate and adaptive immune response to control virus replication and removal from the CNS tissues. The cytokine storm and autoimmune response during the immunological events result in demyelination, damage of resident cells and neurons, cerebrovascular thrombosis, and dysregulation of neuro signaling pathways. Furthermore, hypoxia and toxemia accelerate the neurological destruction process. The acute attributions on psychology due to inflammation is a hallmark of CNS involved pathogenesis; nevertheless, the productivity, durability, and longevity of virus-specific lymphocytes are the vital indicators for complete removal of viral antigen and in combat against reinfection of the CNS. [ABSTRACT FROM AUTHOR]

Epstein‐Barr virus‐associated smooth muscle tumor (EBV‐SMT) is a rare mesenchymal tumor occurred almost exclusively in immunocompromised hosts. This article provides a systematic review of literature under PRISMA guideline on clinical features, treatment modalities, roles of surgical intervention, and outcomes of all 65 reported EBV‐SMTs with central nervous system (CNS) invasion. Over 95% of reported cases were immunocompromised, while human immunodeficiency virus infection and post‐organ transplantation were the most commonly associated underlying causes (near 90%). Despite a heterogeneous follow‐up period, a 1‐year survival rate of 76.0% and 5‐year survival rate of 59.6% may support the indolent and non‐deadly nature of EBV‐SMT even with CNS invasion. Immune survey and reconstruction should be conducted for every patient with CNS EBV‐SMT. Surgical resection is mostly adopted as primary treatment to obtain diagnosis and relieve compressive effect. A total resection of tumor may be beneficial if tumor was symptomatic and had intracranial invasion. [ABSTRACT FROM AUTHOR]

Highlights: [•] Molecular mechanisms of CNS invasion by several neurotropic viruses are compared. [•] Modes by which CHPV could surpass BBB to invade CNS are speculated. [•] Potential CHPV-host protein interactions for experimental research are identified. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) dissemination to the central nervous system (CNS) is a challenging clinical problem whose underlying mechanisms are poorly understood. Here, we show that primary human ALL samples injected into the femora of immunodeficient mice migrate to the skull and vertebral bone marrow and provoke bone lesions that enable passage into the subarachnoid space. Treatment of leukemia xenografted mice with a biologic antagonist of receptor activator of nuclear factor κB ligand (RANKL) blocks this entry route. In addition to erosion of cranial and vertebral bone, samples from individuals with B-ALL also penetrate the blood-cerebrospinal fluid barrier of recipient mice. Co-administration of C-X-C chemokine receptor 4 (CXCR4) and RANKL antagonists attenuate both identified routes of entry. Our findings suggest that targeted RANKL and CXCR4 pathway inhibitors could attenuate routes of leukemia blast CNS invasion and provide benefit for B-ALL-affected individuals., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Simple Summary: Brain invasion has been integrated into the new WHO classification of meningiomas to improve the prognostic assessment regarding tumor recurrence. However, its role has been questioned. One of the reasons is that for complete histopathological assessment, tissue sampling of the complete brain–tumor interface is necessary, but not always surgically and technically feasible. Therefore, the additional intraoperative assessment of CNS invasion may be of value for a more precise assessment of this tumor characteristic. We therefore studied the prognostic impact of the histopathological and intraoperative assessment of CNS invasion regarding radiographic tumor recurrence and found that both factors by themselves do not reach a prognostic significance. However, if both factors are combined, CNS invasion is an independent negative prognostic factor. Our findings show the prognostic potential of a thorough assessment and underline the need for a standardization and documentation of meningioma tissue sampling for the optimal recurrence risk assessment. The detection of the infiltrative growth of meningiomas into CNS tissue has been integrated into the WHO classification as a stand-alone marker for atypical meningioma. However, its prognostic impact has been questioned. Infiltrative growth can also be detected intraoperatively. The prognostic impact of the intraoperative detection of the central nervous system tissue invasion of meningiomas was analyzed and compared to the histopathological assessment. The clinical data of 1517 cases with follow-up data regarding radiographic recurrence was collected. Histopathology and operative reports were reviewed and invasive growth was seen during resection in 23.7% (n = 345) while histopathology detected it in 4.8% (n = 73). The histopathological and intraoperative assessments were compatible in 63%. The prognostic impact of histopathological and intraoperative assessment was significant in the univariate but not in the multivariate analysis. Both methods of assessment combined reached statistical significance in the multivariate analysis (p = 0.0409). A score including all independent prognostic factors divided the cohort into three prognostic subgroups with a risk of recurrence of 33.8, 64.7 and 88.5%, respectively. The intraoperative detection of the infiltrative growth of primary meningiomas into the central nervous system tissue can complement the histopathological assessment of CNS invasion. The combined assessment is an independent prognostic factor regarding tumor recurrence and allows a risk-adapted tumor stratification. [ABSTRACT FROM AUTHOR]

• The BCSFB functions in vivo as an entrance for leukaemic blasts into the CNS. • Discussion of requirements for functional BCSFB models in vitro. • Review of existing in vitro BCSFB models used in leukaemia research. • Evaluation of the reliability and reproducibility of in vitro BCSFB models. • Outlook on developments and implementations to further optimise in vitro BCSFB models. Acute lymphoblastic leukaemia represents the most common paediatric malignancy. Although survival rates approach up to 90% in children, investigation of leukaemic infiltration into the central nervous system (CNS) is essential due to the presence of ongoing fatal complications. Recent in vitro studies mostly employed models of the blood-brain barrier (BBB), as endothelial cells of the microvasculature represent the largest surface between the blood stream and the brain parenchyma. However, crossing the blood-cerebrospinal fluid barrier (BCSFB) within the choroid plexus (CP) has been shown to be a general capability of leukaemic blasts. Hence, in vitro models of the BCSFB to study leukaemic transmigration may be of major importance to understand the development of CNS leukaemia. This review will summarise available in vitro models of the BCSFB employed to study the cellular interactions with leukaemic blasts during cancer cell transmigration into the brain compartment across primary or immortal/immortalised BCSFB cells. It will also provide an outlook on prospective improvements in BCSFB in vitro models by developing barrier-on-a-chip models and brain organoids. [ABSTRACT FROM AUTHOR]

Microglia are neural cells of nonneural origin; they originate from fetal macrophages that invade neural tube early in embryogenesis and undergo the most idiosyncratic metamorphosis which coverts them into elements of neural circuitry. Microglia appeared early in evolution with neural immune cells being operative in leeches and mollusks. Microglial cells acquire specific morphology characterized by small cell bodies and long motile processes which are packed with receptors sensing both physiological and pathological stimuli. Microglial cells actively sculpture neuronal networks through synaptic stripping and phagocytosis of redundant neurons; microglia also secrete neuroactive factors regulating synaptic transmission. Novel techniques emerging in recent decade allowed an in-depth understanding of physiological and pathophysiological functions of microglia.