Nerve Sheath Research Articles

Late-onset tumors in rhabdoid tumor predisposition syndrome type-1 (RTPS1) and implications for surveillance.

Rhabdoid tumor predisposition syndrome type-1 (RTPS1) is characterized by germline pathogenic variants in SMARCB1 and development of INI1-deficient rhabdoid tumors in early childhood. Due to its poor prognosis, the risk of subsequent tumor development and the impact of surveillance at later ages are poorly understood. We retrospectively reviewed individuals referred to the Cancer Genetics Program at The Hospital for Sick Children for SMARCB1 genetic testing and/or surveillance for RTPS1. In addition, to explore characteristics of late-onset tumors in RTPS1, a literature review was conducted. Of eighty-three individuals (55 probands and 28 family members), 12 probands and 4 family members were genetically confirmed with RTPS1. Four pediatric probands with RTPS1 underwent surveillance. An additional three individuals, including one patient with 22q11.2 distal deletion without history of tumor, one patient with negative genetic testing results but clinically diagnosed with RTPS1, and one sibling identified through cascade testing, underwent surveillance. Three patients with RTPS1 developed tumors between the ages of 9 and 17, including malignant rhabdoid tumors (N = 3), schwannomas (N = 4), and epithelioid malignant peripheral nerve sheath tumor (N = 1). Three of these lesions were asymptomatically detected by surveillance. A literature review revealed 17 individuals with RTPS1 who developed INI1-deficient tumors after age five. Individuals with RTPS1 remain at elevated risk for developing INI1-deficient tumors after the peak age of rhabdoid tumor in early childhood. Extension of surveillance beyond 5 years of age could lead to improved survival and reduced morbidity for these patients, and prospective evaluation of revised approaches will be important.

Optic nerve sheath measurement to monitor disease activity in giant cell arteritis: a pilot study

Introduction/ObjectivesOptic nerve sheath (ONS) enhancement using magnetic resonance imaging of the orbits was observed in patients with giant cell arteritis (GCA). We previously showed that ONS diameter (ONSD) by bedside ultrasound is increased in patient with active GCA. This study aims to assess whether ONSD decreases with clinical remission in patients with GCA.MethodsA prospective cohort study was conducted from June 2022 to January 2023. Patients who had an optic nerve ultrasound at GCA diagnosis as part of a previous crosssectional study were eligible. Optic nerve ultrasound was performed by the same investigator at diagnosis and month 3. ONSD (includes the optic nerve and its sheath) and optic nerve diameter (OND) were measured. Descriptive statistics for baseline characteristics and paired sample t-test were performed to assess the mean difference in OND and ONSD between diagnosis and month 3.ResultsNine patients with GCA were included. The median age at disease onset was 79 years (interquartile range (IQR) of 79–82 years), and 7 patients were males. All patients were in clinical remission at month 3 on prednisone (median dose of 15 mg/day, IQR of 10–25 mg). The mean ONSD was lower at month 3 (3.76 mm) compared to baseline (5.98 mm), with a paired mean difference of 2.22 mm (95% CI 1.41–3.03 mm, p < 0.001). As anticipated, OND measurements did not vary between diagnosis and month 3.ConclusionONSD on ultrasound improves after 3 months of therapy in patients with GCA. A longer prospective study is required to determine if ONSD is useful to assess disease activity in GCA.Key Points• ONS ultrasound can identify patients with active GCA.• The ONSD on ultrasound is dynamic and improved after 3 months of GCA therapy.• ONS ultrasound may be useful to monitor disease activity in GCA.

Optic nerve sheath diameter measurement using ultrasonography: associations with in-hospital mortality in COVID-19 intensive care unit admissions.

Optic nerve sheath diameter measurement using ultrasonography: associations with in-hospital mortality in COVID-19 intensive care unit admissions.

Multiparametric whole-body MRI of patients with neurofibromatosis type I: spectrum of imaging findings.

Neurofibromatosis (NF) type I is a neuroectodermal and mesodermal dysplasia caused by a mutation of the neurofibromin tumor suppressor gene. Phenotypic features of NF1 vary, and patients develop benign peripheral nerve sheath tumors and malignant neoplasms, such as malignant peripheral nerve sheath tumor, malignant melanoma, and astrocytoma. Multiparametric whole-body MR imaging (WBMRI) plays a critical role in disease surveillance. Multiparametric MRI, typically used in prostate imaging, is a general term for a technique that includes multiple sequences, i.e. anatomic, diffusion, and Dixon-based pre- and post-contrast imaging. This article discusses the value of multiparametric WBMRI and illustrates the spectrum of whole-body lesions of NF1 in a single imaging setting. Examples of lesions include those in the skin (tumors and axillary freckling), soft tissues (benign and malignant peripheral nerve sheath tumors, visceral plexiform, and diffuse lesions), bone and joints (nutrient nerve lesions, non-ossifying fibromas, intra-articular neurofibroma, etc.), spine (acute-angled scoliosis, dural ectasia, intraspinal tumors, etc.), and brain/skull (optic nerve glioma, choroid plexus xanthogranuloma, sphenoid wing dysplasia, cerebral hamartomas, etc.). After reading this article, the reader will gain knowledge of the variety of lesions encountered with NF1 and their WBMRI appearances. Timely identification of such lesions can aid in accurate diagnosis and appropriate patient management.

Changes in optic nerve sheath diameter and its correlation with degree of consciousness, pupil diameter, and light reflex in children with central nervous system infection after osmotherapy.

High intracranial pressure (ICP) is one of the most common complications of central nervous system (CNS) infection. Failure to control high intracranial pressure results in brain herniation and death. One of the treatments for high ICP involves the administration of osmotherapy in the form of 3% NaCl or 20% mannitol with observation during administration. Observation of ICP during administration of osmotherapy is possible through measurement of optic nerve sheath diameter (ONSD), which could be correlated with degree of consciousness, pupil diameter, and light reflex. Previous studies have not correlated ONSD with degree of consciousness, pupil diameter, and light reflex during the administration of osmotherapy. To provide insights of incorporating ONSD measurement as a form of non-invasive bedside method for ICP monitoring by correlating it with degree of consciousness, pupil diameter, and light reflex at several time points. This study is a prospective cohort study, performed at Dr. Hasan Sadikin General Central Hospital Bandung, Cibabat General Regional Hospital, and General Regional Hospital Bandung Kiwari on children aged 2-18 years with decreased consciousness and CNS infection, from June 2023. Inter-rater reliability was performed with a correlation coefficient of 0.90. Measurement of ONSD, degree of consciousness, pupil diameter, and light reflex simultaneously up to 48 h after initiation of osmotherapy to 30 patients. Correlational analyses were performed using Spearman's rank. Observation for 48 h after administration of osmotherapy showed changes in ONSD. A significant positive correlation was found between ONSD and degree of consciousness (r = 0.621 for the right eye and r = 0.602 for the left eye, p < 0.001). A significant positive correlation was found between ONSD and light reflex (r = 0.801 for the right eye and r = 0.812 for the left eye, p < 0.001). No significant correlation was found with changes of pupil diameter (r = -0.136 for the right eye and r = -0.141 for the left eye, p > 0.05). A significant correlation was found between ONSD and degree of consciousness and light reflex in children aged 2-18 years with CNS infection during administration of osmotherapy.

Investigating therapeutic nonsense suppression in a neurofibromatosis mouse model

Neurofibromatosis type 1 (NF1) is a human genetic disorder caused by variants in the NF1 gene. Plexiform neurofibromas, one of many NF1 manifestations, are benign peripheral nerve sheath tumors occurring in up to 50% of NF1 patients. A substantial fraction of NF1 pathogenetic variants are nonsense mutations, which result in the synthesis of truncated non-functional NF1 protein (neurofibromin). To date, no therapeutics have restored neurofibromin expression or addressed the consequences of this protein's absence in NF1 nonsense mutation patients, but nonsense suppression is a potential approach to the problem. Ataluren is a small molecule drug that has been shown to stimulate functional nonsense codon readthrough in several models of nonsense mutation diseases, as well as in Duchenne muscular dystrophy patients. To test ataluren's potential applicability in nonsense mutation NF1 patients, we evaluated its therapeutic effects using three treatment regimens in a previously established NF1 patient-derived (c.2041C > T; p.Arg681X) nonsense mutation mouse model. Collectively, our experiments indicate that: i) ataluren appeared to slow the growth of neurofibromas and alleviate some paralysis phenotypes, ii) female Nf1-nonsense mutation mice manifested more severe paralysis and neurofibroma phenotypes than male mice, iii) ataluren doses with apparent effectiveness were lower in female mice than in male mice, and iv) age factors also influenced ataluren's effectiveness.

Role of neuroimaging markers on predicting of idiopathic intracranial hypertension.

The goals of neuroimaging in idiopathic intracranial hypertension (IIH) are the exclusion of mimickers and effective management of disease. In recent studies, several imaging markers have been identified as potential predictors of IIH. To investigate the predictive roles of novel radiological markers as the Meckel's cave area, alongside classical radiologic markers in identifying IIH such as the empty sella. The patients were classified according to cerebrospinal fluid (CSF) opening pressure as the IIH group and control group. The observational, case-control study included 22 patients with IIH and 22 controls. Groups were compared for presence of empty sella, Meckel's cave area, fat area of posterior neck, fat thickness of scalp, presence of transverse sinus stenosis, and ophthalmic markers, such as increase of optic nerve (ON) sheath diameter. In the IHH group, higher occurrences of increased ON sheath diameter, ON tortuosity, flattening of the scleral surface, and transverse sinus stenosis were observed (P < 0.001, P < 0.001, P = 0.046, and P = 0.021, respectively). Meckel's cave area and fat area of posterior neck were similar in both groups (P = 0.444 and P = 0.794). Ophthalmic markers and transverse sinus stenosis could be utilized as radiologic features supporting early and precise diagnosis of IIH. However, enlargement of Meckel's cave area and measurements of fatty area of posterior neck are not helpful for diagnosis of IIH.

A Prediction Model for Detecting Dysthyroid Optic Neuropathy Based on Clinical Factors and Imaging Markers of the Optic Nerve and Cerebrospinal Fluid in the Optic Nerve Sheath.

This study aimed to develop and test a model for predicting dysthyroid optic neuropathy (DON) based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid (CSF) in the optic nerve sheath. This retrospective study included patients with thyroid-associated ophthalmopathy (TAO) without DON and patients with TAO accompanied by DON at our hospital. The imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and, together with clinical factors, were screened by Least absolute shrinkage and selection operator. Subsequently, we constructed a prediction model using multivariate logistic regression. The accuracy of the model was verified using receiver operating characteristic curve analysis. In total, 80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our study. Two variables (optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath) were found to be independent predictive factors and were included in the prediction model. In the development cohort, the mean area under the curve (AUC) was 0.994, with a sensitivity of 0.944, specificity of 0.967, and accuracy of 0.901. Moreover, in the validation cohort, the AUC was 0.960, the sensitivity was 0.889, the specificity was 0.893, and the accuracy was 0.890. A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath, serving as a noninvasive potential tool to predict DON.

Ultrasonographic Assessment of Optic Nerve Sheath Diameter as a Screening Tool for Intracranial Hypertension in Traumatic Brain Injury

BackgroundSevere traumatic brain injury (TBI) is a condition burdened by high morbidity and mortality. Prevention of secondary insults is one of the main goals of management and intracranial pressure monitoring is a cornerstone in management of TBI. The relationship between intracranial pressure and optic nerve sheath is known from the literature. Optic nerve sheath ultrasonography could represent a method added to our armamentarium for monitoring intracranial pressure. MethodsWe investigated how ultrasound-measured optic nerve sheath diameter varies as a function of intracranial pressure in a cohort of patients with severe blunt head injury in whom an intraparenchymal sensor was placed. We evaluated the accuracy of optic nerve sheet diameter (ONSD) in distinguishing dichotomized ICP cut-offs and analyzed the learning curve and its potential as screening tool to select TBI patients most in need of invasive ICP monitoring in a setting with constraints on resources. ResultsONSD and ICP have a linear relationship. Nevertheless, there are limits of evaluating the one-to-one correspondence between those two variables. We selected a cut-off of sonographic ONSD above which there is a concernable elevation of intracranial pressure (ICP>15 mmHg) worthy of invasive second line invasive monitoring. Thus, it is possible to use ONSD as a first line non-invasive tool to intercept patients at risk of developing frank intracranial hypertension. ConclusionsWe propose the use of ONSD ultrasound as a screening investigation for post-traumatic intracranial hypertension in the context of an emergency department, especially in contexts where there is limited availability of intracranial pressure monitors.

Radiologic Predictors of Visual Outcome in Myelin Oligodendrocyte Glycoprotein-Related Optic Neuritis

This study aimed to determine whether magnetic resonance imaging (MRI) biomarkers are associated with visual prognosis in myelin oligodendrocyte protein (MOG)-associated optic neuritis (ON). Cross-sectional analysis. Patients meeting 2023 international diagnostic criteria for MOG antibody-associated disease who were seen for first episodes of MOG-associated ON at 3 tertiary neuro-ophthalmology practices between January 2017 and July 2023 were enrolled. Patients who received < 3 months of neuro-ophthalmic follow-up and did not demonstrate visual recovery (visual acuity [VA] ≥ 20/20 and visual field mean deviation [VFMD] > -5.0 dB) during this time were excluded. Patients underwent contrast-enhanced, fat-suppressed MRI of the brain and orbits within 1 month of symptom onset. The associations between radiologic biomarkers and poor VA outcome (<20/40), incomplete VA recovery (< 20/20), and poor VFMD outcome (VFMD < -5.0 dB) were assessed using multivariable logistic regression adjusting for time from symptom onset to treatment and nadir VA or VFMD. Radiologic biomarkers included length of optic nerve enhancement (> 25% vs. < 25%; > 50%vs.<50%; and >75%vs.< 75%); degree of orbital, canalicular, and intracranial or chiasmal optic nerve enhancement (mild vs. moderate to severe compared with the lacrimal gland); and absence versus presence of optic nerve sheath enhancement on baseline T1-weighted MRI. A total of 129 eyes of 92 patients (median age, 37.0 years [interquartile range, 20.8-51.3 years]; 65.2% female) were included. Poor VA outcome was seen in 6.2% of patients, incomplete VA recovery was seen in 19.4% of patients, and poor VFMD outcome was seen in 16.9% of patients. Compared with eyes with moderate to severe enhancement, eyes with mild orbital optic nerve enhancement were more likely to have poor VA outcome (odds ratio [OR], 8.57; 95% confidence interval [CI], 1.85-51.14; P= 0.009), incomplete VA recovery (OR, 7.31, 95% CI, 2.42-25.47; P= 0.001), and poor VFMD outcome (adjusting for time to treatment: OR, 6.81; 95% CI, 1.85-28.98; P= 0.005; adjusting for nadir VFMD: OR, 11.65; 95% CI, 1.60-240.09; P= 0.04). Lack of optic nerve sheath enhancement additionally was associated with incomplete VA recovery (OR, 3.86; 95% CI, 1.19-12.85; P= 0.02) compared with the presence of enhancement. These associations remained consistent in subgroup logistic regression analysis of MRIs performed before initiation of treatment but were not seen in pairwise analysis of MRIs performed after treatment. In eyes with first MOG-associated ON episodes, milder enhancement in the orbital optic nerve was associated with poorer VA and visual field recovery. Prospective and mechanistic studies are needed to confirm the prognostic usefulness of MRI in MOG-associated ON. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effect of rapid maxillary expansion on intracranial pressure

ObjectiveThe aim of this study was to evaluate the effects of rapid maxillary expansion on the optic nerve sheath diameter and to examine its possible effects on intracranial pressure. Design20 patients with bilateral crossbite were selected. Hyrax Expander was applied and activated twice daily until the overcorrection was achieved. The optic nerve sheath diameter (ONSD) was measured via ultrasonography before the first activation (T0), then repeated after 1 (T1) and 10 min (T2). At the end of the expansion, ONSD was measured (T3) again, then the screw was activated for the last time, and measurements were repeated after 1 (T4) and 10 min (T5). The Friedman test was performed to compare the changes, and The Wilcoxon Signed-Rank test was done to determine the significant intergroup changes (p < 0.05). ResultsThe ONSD increased significantly 1 min after the activations (T0-T1 and T3-T4) (P < 0.05). The ONSD values measured 10 min after the activations also increased significantly compared to the baseline values (T0-T2 and T3-T5) (P < 0.05). ConclusionThe activation of maxillary expansion appliances increased the optic nerve sheath diameter in adolescents. Therefore, orthodontists should be careful with patients at risk of intracranial hypertension.

Chemical genetic screens reveal defective lysosomal trafficking as synthetic lethal with NF1 loss.

Neurofibromatosis type 1, a genetic disorder caused by pathogenic germline variations in NF1, predisposes individuals to the development of tumors, including cutaneous and plexiform neurofibromas (CNs and PNs), optic gliomas, astrocytomas, juvenile myelomonocytic leukemia, high-grade gliomas and malignant peripheral nerve sheath tumors (MPNSTs), which are chemotherapy- and radiation-resistant sarcomas with poor survival. Loss of NF1 also occurs in sporadic tumors, such as glioblastoma (GBM), melanoma, breast, ovarian and lung cancers. We performed a high-throughput screen for compounds that were synthetic lethal with NF1 loss, which identified several leads, including the small molecule Y102. Treatment of cells with Y102 perturbed autophagy, mitophagy and lysosome positioning in NF1-deficient cells. A dual proteomics approach identified BLOC-one-related complex (BORC), which is required for lysosome positioning and trafficking, as a potential target of Y102. Knockdown of a BORC subunit using siRNA recapitulated the phenotypes observed with Y102 treatment. Our findings demonstrate that BORC might be a promising therapeutic target for NF1-deficient tumors.

Computed Tomography Optic Nerve Sheath Diameter-to-Eyeball Transverse Diameter Ratio as a Novel Noninvasive Parameter for Prognostication in Traumatic Brain Injury.

Background Traumatic brain injury (TBI) remains a foremost cause of death and disability globally, with elevated intracranial pressure (ICP) being a crucial factor in patient outcomes. While invasive monitoring is the gold standard for assessing ICP, it carries risks and is not always feasible. This study proposes a novel noninvasive parameter using computed tomography (CT) imaging. Aims and objectives The study aims to determine the efficacy of the optic nerve sheath diameter (ONSD)-to-eyeball transverse diameter (ETD) ratio from CT scans in predicting TBI patients' prognosis. The primary objective is to study the ONSD/ETD ratio's efficacy in assessing TBI's severity. The secondary objective is to correlate the ONSD/ETD ratio with the Glasgow Coma Scale (GCS) and Rotterdam computed tomography scoring (RCTS) and assess its clinical benefit. Materials and methods This combined retrospective and prospective analytical study included 308 consecutive patients who underwent CT imaging for TBI at a tertiary care center with a dedicated trauma and neurosurgical unit. We evaluated bilateral ONSD and ETD using axial CT scans. The ONSD/ETD ratio correlated with the GCS, RCTS, and clinical outcomes. Results The cut-off values for elevated ICP were ONSD of >5.17 mm, ETD of <22.2 mm, and ONSD/ETD ratio of >0.21. Variables between GCS (<12 and >12) and the ONSD/ETD ratio (<0.21 and >0.21) were statistically significant (chi-square {χ2} = 18.52, p = 0.000). The ONSD shows a strong positive correlation with RCTS (r = 0.82, p = 0.01), ETD shows a moderate negative correlation with RCTS (r = -0.50), and the ONSD/ETD ratio shows a strong negative correlation with GCS (r = -0.783, p = 0.01). The area under the curve for the ONSD/ETD ratio (0.920) was higher than that for ONSD (0.932) and ETD (0.490). The ONSD/ETD ratio's sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 95.6%, 72.0%, and 100%, respectively, demonstrating that it is an excellent predictor of raised ICP. Conclusion The CT-ONSD/ETD ratio correlates with the severity of TBI as assessed by GCS and RCTS. It could serve as a noninvasive parameter for monitoring ICP and guiding the need for sequential CT in TBI patients, potentially aiding in prognostication and clinical management.

Innovations in the classification of soft tissue tumors

Soft tissue tumors are avery heterogeneous group of tumors. Their classification is regularly updated by the World Health Organization (WHO), most recently in 2020. The current classification of soft tissue tumors emphasizes molecular biological tumor characteristics, which enable tumor-specific treatment. In addition to Ewing's sarcoma, which occurs as bone as well as extra-skeletal soft tissue tumors as asmall round cell sarcoma, three other subtypes of undifferentiated, small and round cell sarcomas have been introduced. Some names of the new sarcomas can be derived from the gene mutations. The groups of adipocytic and (myo)fibroblastic tumors have been extended by three further entities. There were further additions to vascular soft tissue tumors, smooth muscle cell tumors, peripheral nerve sheath tumors and tumors of uncertain differentiation. Adistinction is made between benign, intermediate locally aggressive, intermediate rarely metastatic and malignant soft tissue tumors.

A Rare Case of Subconjunctival Nerve Sheath Myxoma Presenting as Orbital Fat Prolapse.

Nerve sheath myxomas are extremely rare myxoid peripheral nerve sheath tumors with a predilection for the distal extremities, particularly common in the fingers and knees. Here, we report a 60-year-old male patient with a subconjunctival epibulbar nerve sheath myxoma, which was clinically diagnosed as an orbital fat prolapse. The lesion was successfully debulked without clinical recurrence over more than 3 years. To our knowledge, this is the first case with subconjunctival presentation and fourth orbital reported case.

Transmembrane protein 53 craniotubular dysplasia (OMIM # 619727): The skeletal disease and consequent blindness of this new disorder

Craniotubular dysplasia, Ikegawa type (OMIM #619727) denotes the autosomal recessive skeletal disease identified in 2021 featuring blindness acquired in childhood. Five young members of four Indian families harbored a homozygous indel within TMEM53 (OMIM *619722), the gene that encodes transmembrane protein 53 (TMEM53). When intact, TMEM53 spans the nuclear envelope of osteoprogenitor cells, dampens BMP-SMAD signaling, and thereby slows bone formation. Consequently, defective TMEM53 accelerates osteogenesis. Herein, an American boy is compound heterozygous for a novel deletion and a novel missense mutation within TMEM53. His vision and sensorineural hearing became impaired. Radiographic survey revealed diploic thickening of his skull, broad calvarial and facial bones, skeletal modeling errors, vertebral body flattening, wide ribs, and osteopenia of expanded bones. DXA areal bone density (gm/cm2) Z-scores were low. His optic, auditory, and spinal canals were narrow. Mineral metabolism was intact. Serum alkaline phosphatase and osteocalcin levels were normal yet CTX was high. Iliac crest histomorphometry documented accelerated bone formation. His acute vision loss briefly improved following prednisone administration, optic canal decompression, and optic nerve sheath fenestration, but then progressed despite further surgeries and zoledronate treatment aimed to suppress bone turnover. Next generation sequencing of genes associated with elevated skeletal mass, including from high bone turnover, did not suggest an etiology. Whole genome sequencing then revealed within TMEM53: i) a paternally transmitted 54-base deletion, which included the mRNA splice acceptor site for exon 2 as well as 31 bases of exonic sequence (c. 62-23_92del), and ii) a maternally transmitted missense variant (c.650C > T, p.Ser217Leu: NM_024587.4/NP_078863.2) which is extremely rare in gnomAD (frequency = 0.000036), replaces Ser217 highly conserved across species, and is scored as damaging by SIFT and Mutation Taster. We call this new osteopathy TMEM53 craniotubular dysplasia.

TRPS1 expression in MPNST is correlated with PRC2 inactivation and loss of H3K27me3

Initially described as a highly specific immunohistochemical marker for carcinomas of mammary origin, trichorhinophalangeal syndrome type 1 (TRPS1) has subsequently been detected in a variety of other non-mammary tumors. In this study, we examined the immunohistochemical expression of TRPS1 in 114 peripheral nerve sheath tumors, including 43 malignant peripheral nerve sheath tumors (MPNSTs), 58 schwannomas, including 9 cellular neurofibromas, and 13 neurofibromas, including 1 atypical neurofibroma. Notably, TRPS1 was expressed in 49% of MPNSTs and was absent in all schwannomas and neurofibromas. All MPNSTs showed TRPS1 labeling in >50% of nuclei, with 95% of cases demonstrating diffuse labeling. Most cases (67%) showed weak TRPS1 immunoreactivity, while a smaller subset showed moderate (24%) or strong (9%) intensity staining. Analysis of publicly available gene expression datasets revealed higher levels of TRPS1 mRNA in MPNSTs with PRC2 inactivation. In keeping with this finding, TRPS1 expression was more commonly observed in MPNSTs with loss of H3K27me3, suggesting a potential relationship between TRPS1 and the PRC2 complex. This study further broadens the spectrum of TRPS1-expressing tumors to include MPNST.

Primary BAP1-absent atypical meningioma arising from median nerve within infraclavicular brachial plexus: illustrative case.

The authors present the only known case of a World Health Organization grade II ectopic meningioma occurring in the infraclavicular brachial plexus, causing pain within the axilla not associated with a primary malignant meningioma of the central nervous system. Peripheral nerve sheath tumors are rare entities, the majority of which are schwannomas or neurofibromas. Ectopic meningiomas only represent 1%-2% of all meningiomas. To date, there is one other published case specifically of a primary ectopic meningioma located in the brachial plexus. Following the dissection of the left axilla, a dominant rubbery tumor involving the median nerve was encountered. The tumor capsule contained areas of hemorrhage and a soft core with nerve fascicles coursing through, which were not compromised during internal tumor debulking. The tumor lacked a clear pseudocapsule that is characteristically seen in schwannomas. Histopathological studies confirmed an atypical epithelioid neoplasm with elevated numbers of mitotic figures and BAP1 gene deletion. Primary meningiomas arising outside the central nervous system are exceedingly rare. For this unusual higher-grade primary ectopic meningioma located in the distal brachial plexus, surgery with the goal of gross-total resection, adjuvant radiation, additional imaging, and genetics screening were recommended. Close follow-up is warranted. https://thejns.org/doi/10.3171/CASE24226.

Reconceiving Perineural Invasion in Cutaneous Squamous Cell Carcinoma: From Biological to Histopathological Assessment.

Perineural invasion (PNI) is a complex molecular process histologically represented by the presence of tumor cells within the peripheral nerve sheath and defined when infiltration into the 3 nerve sheath layers can be clearly identified. Several molecular pathways have been implicated in cSCC. PNI is a well-recognized risk factor in cutaneous squamous cell carcinoma (cSCC) and its accurate assessment represents a challenging field in pathology daily practice. As a highly intricate and dynamic process, PNI involves a contingent on bidirectional signaling interactions between the tumor and various nerve components, such as Schwann cells and neurons. The current staging systems recommend the identification of PNI as a dichotomous variable (presence vs. absence) to identify a subgroup of high-risk patients. However, recent further insights revealed that the evaluation of morphological PNI-related features in cSCC may enhance the prognostic stratification of patients and may optimize the current staging guidelines for recurrence risk assessment and improvement of patient selection for postoperative adjuvant treatments. Furthermore, recent emerging biomarkers could redefine early PNI detection. This review provides updated insights into cSCC with PNI, focusing on molecular and cellular pathogenic processes, and aims to increase knowledge on prognostic relevant PNI-related histological features.

Optic Nerve Sheath Measurement on Ultrasound: A Novel Diagnostic Test for Giant Cell Arteritis.

Optic nerve sheath enhancement on magnetic resonance imaging has been reported in patients with giant cell arteritis (GCA), with or without visual manifestations. Whether similar findings can be documented on ultrasound is unknown. Optic nerve ultrasound is a point-of-care, easy to learn, rapid, and noninvasive technique. This study aims to investigate whether optic nerve sheath diameter (ONSD) measured on ultrasound is useful in the diagnosis of active, new-onset GCA. A single-center, diagnostic accuracy study was performed from June to November 2022 on consecutive eligible patients referred for suspected GCA. Optic nerve ultrasound was performed on both eyes. The ONSD (includes the optic nerve and its sheath) and optic nerve diameter (OND) were measured 3 mm behind the ocular globe. The presence or absence of GCA was confirmed clinically 6 months later. Multivariable linear regression, adjusting for age and sex, was used to determine the association between optic nerve ultrasound measures and final GCA diagnosis. Thirty participants were enrolled, including nine participants with a final diagnosis of GCA. Mean ± SD ONSD was 5.98 ± 1.17 mm in patients with GCA and 4.02 ± 0.99 mm in patients without GCA. Mean ONSD was greater by 1.26 mm in patients with GCA (95% confidence interval 0.30-2.21 mm, P = 0.01) compared with those without GCA, adjusting for age and sex. Mean ± SD OND was 2.97 ± 0.46 mm in patients with GCA and 2.47 ± 0.58 mm in patients without GCA. There was no evidence of an association between GCA diagnosis and OND. Patients with GCA had a significantly greater ONSD on ultrasound than patients without GCA. Optic nerve ultrasound may represent a novel, rapid, bedside diagnostic test for GCA. A large prospective study is required to confirm these findings and evaluate whether ONSD can be used as a disease activity biomarker in GCA.