Focused update to guidelines for endovascular therapy for emergent large vessel occlusion: basilar artery occlusion patients.

BACKGROUND: Endovascular therapy (EVT) dramatically improves clinical outcomes for patients with anterior circulation emergent large vessel occlusion (ELVO) strokes. With recent publication of two randomized controlled trials in favor of EVT for basilar artery occlusions, the Society of NeuroInterventional Surgery (SNIS) Standards and Guidelines Committee provides this focused update for the existing SNIS guideline, 'Current endovascular strategies for posterior circulation large vessel occlusion stroke.' METHODS: A structured literature review and analysis of studies related to posterior circulation large vessel occlusion (basilar or vertebral artery) strokes treated by EVT was performed. Based on the strength and quality of the evidence, recommendations were made by consensus of the writing committee, with additional input from the full SNIS Standards and Guidelines Committee and the SNIS Board of Directors. RESULTS: Based on the results of the most recent randomized, controlled trials on EVT for basilar or vertebral artery occlusion, the expert panel agreed on the following recommendations. For patients presenting with an acute ischemic stroke due to an acute basilar or vertebral artery occlusion confirmed on CT angiography, National Institutes of Health Stroke Scale (NIHSS) score of ≥6, posterior circulation Alberta Stroke Program Early CT Score (PC-ASPECTS) ≥6, and age 18-89 years: (1) thrombectomy is indicated within 12 hours since last known well (class I, level B-R); (2) thrombectomy is reasonable within 12-24 hours from the last known well (class IIa, level B-R); (3) thrombectomy may be considered on a case by case basis for patients presenting beyond 24 hours since last known well (class IIb, level C-EO). In addition, thrombectomy may be considered on a case by case basis for patients aged <18 years or >89 years on a case by case basis (class IIb, level C-EO). CONCLUSIONS: The indications for EVT of ELVO strokes continue to expand and now include patients with basilar artery occlusion. Further prospective, randomized controlled trials are warranted to elucidate the efficacy and safety of EVT in populations not included in this set of recommendations, and to confirm long term outcomes.

Rapid presentation of a de novo intracranial aneurysm: illustrative case.

BACKGROUND: Intracranial aneurysms are prevalent, particularly with advancing age. De novo aneurysms, occurring independently from the initial lesion, pose a unique challenge because of their unpredictable nature. Although risk factors such as female sex, smoking history, and hypertension have been proposed, the mechanisms underlying de novo aneurysm development remain unclear. OBSERVATIONS: A 79-year-old female developed a de novo saccular aneurysm within a year after management of a ruptured vertebral artery dissecting aneurysm. Her complex clinical course involved subarachnoid hemorrhage with diffuse vasospasm, stent occlusion of a dissecting aneurysm, discovery of a right 7- to 8-mm de novo middle cerebral artery aneurysm at the 1-year magnetic resonance angiography follow-up, and successful coil embolization. LESSONS: This rare occurrence challenges established timelines, as most de novo aneurysms manifest over a longer interval. Studies have attempted to identify risk factors, yet consensus remains elusive, particularly regarding the influence of treatment modality on de novo formation rates. This unique case urges reconsideration of posttreatment surveillance protocols, proposing shorter intervals for imaging and more vigilant follow-up strategies to detect asymptomatic de novo aneurysms. Timelier identification could significantly impact patient outcomes by averting potential ruptures. This emphasizes the need for further research to delineate effective monitoring and preventive measures for these enigmatic lesions.

Endovascular therapy for anterior circulation emergent large vessel occlusion stroke in patients with large ischemic cores: a report of the SNIS Standards and Guidelines Committee.

BACKGROUND: Early clinical trials validating endovascular therapy (EVT) for emergent large vessel occlusion (ELVO) ischemic stroke in the anterior circulation initially focused on patients with small or absent completed infarctions (ischemic cores) to maximize the probability of detecting a clinically meaningful and statistically significant benefit of EVT. Subsequently, real-world experience suggested that patients with large core ischemic strokes (LCS) at presentation may also benefit from EVT. Several large, retrospective, and prospective randomized clinical trials have recently been published that further validate this approach. These guidelines aim to provide an update for endovascular treatment of LCS. METHODS: A structured literature review of LCS studies available since 2019 and grading the strength and quality of the evidence was performed. Recommendations were made based on these new data by consensus of the authors, with additional input from the full SNIS Standards and Guidelines Committee and the SNIS Board of Directors. RESULTS: The management of ELVO strokes with large ischemic cores continues to evolve. The expert panel agreed on several recommendations: Recommendation 1: In patients with anterior circulation ELVO who present within 24 hours of last known normal with large infarct core (70-149 mL or ASPECTS 3-5) and meet other criteria of RESCUE-Japan LIMIT, SELECT2, ANGEL-ASPECT, TESLA, TENSION, or LASTE trials, thrombectomy is indicated (Class I, Level A). Recommendations 2-7 flow directly from recommendation 1. Recommendation 2: EVT in patients with LCS aged 18-85 years is beneficial (Class I, Level A). Recommendation 3: EVT in patients with LCS >85 years of age may be beneficial (Class I, Level B-R). Recommendation 4: Patients with LCS and NIHSS score 6-30 benefit from EVT in LCS (Class I, Level A). Recommendation 5: Patients with LCS and NIHSS score <6 and >30 may benefit from EVT in LCS (Class IIa, Level A). Recommendation 6: Patients with LCS and low baseline mRS (0-1) benefit from EVT (Class I, Level A). Recommendation 7: Patients with LCS and time of last known well 0-24 hours benefit from EVT (Class I, Level A). Recommendation 8: It is recommended that patients with ELVO LCS who also meet the criteria for on-label or guideline-directed use of IV thrombolysis receive IV thrombolysis, irrespective of whether endovascular treatments are being considered (Class I, Level B-NR). CONCLUSIONS: The indications for endovascular treatment of ELVO strokes continue to expand and now include patients with large ischemic cores on presentation. Further prospective randomized studies, including follow-up to assess the population-based efficacy of treating patients with LCS, are warranted.

Lumbar decompression and fusion for symptomatic spinal stenosis in a patient with chronic thoracic sensory level from prior transverse myelitis: a case report.

BACKGROUND: Many patients with transverse myelitis suffer from sensory loss below the spinal level of the lesion. This is commonly associated with chronic neuropathic pain. However, the presence of somatic pain below a complete thoracic sensory level after transverse myelitis is exceptionally rare, and it is unclear if surgical decompression is an effective form of treatment for these patients. CASE PRESENTATION: In this report, we describe a 22-year-old Caucasian female who suffered from chronic lumbar back pain despite a complete thoracic sensory level secondary to prior transverse myelitis. Imaging demonstrated multilevel central stenosis below the sensory level, and her pain improved after surgical decompression. To our knowledge, this is the first reported case of symptomatic lumbar stenosis below a sensory level after transverse myelitis successfully treated with surgical decompression. CONCLUSION: This is the first reported case of a patient with symptomatic lumbar stenosis after transverse myelitis whose lower back pain and quality of life improved following surgical decompression and fusion. This case provides evidence that typical lumbago is possible in patients with sensory loss from transverse myelitis, and standard lumbar decompression may provide benefit for these patients.

Sir Rickman John Godlee-Contributions in Addition to His 1884 Tumor Resection, A Review.

BACKGROUND: Sir Rickman John Godlee (1849-1925) was widely known for performing the first documented surgery to resect a tumor from the brain. METHODS: The case was performed on November 25, 1884, on a 25-year-old farmer who presented with a left-sided Jacksonian March seizure. RESULTS: The case was highly publicized because the tumor was localized by Dr. Hughes Bennett and subsequently resected by Sir Godlee based on the patient's clinical presentation and physical examination alone. CONCLUSIONS: Aside from this widely publicized case, little has been written about Sir Godlee. Sir Godlee was also known to be an outstanding anatomist who displayed exceptional skills in surgical dissection. He was known for being an excellent teacher. Sir Godlee was deeply influenced by his uncle, Lord Joseph Lister, a renowned physician who popularized antiseptic methods. Sir Godlee was also known for publishing his uncle's biography, Lord Lister.

Genomic characterization of an esthesioneuroblastoma with spinal metastases: illustrative case.

BACKGROUND: Esthesioneuroblastoma (ENB) is a rare neoplasm of the sinonasal tract. Currently, the optimal treatment includes maximal resection combined with radiotherapy and/or chemotherapy. Although ENBs often recur and have an aggressive clinical course, spinal metastases are extremely rare and the underlying molecular mechanisms are poorly understood. OBSERVATIONS: Here, the authors describe a 50-year-old male with an aggressive ENB, initially treated with resection and chemotherapy/radiation, who developed multiple thoracic and lumbar spinal metastases. The authors performed targeted exome sequencing on both the resected primary tumor and biopsied spinal metastases, which revealed 12 total variants of unknown clinical significance in genes associated with the PI3K/AKT/mTOR pathway, chromatin remodeling, DNA repair, and cell proliferation. Six of these variants were restricted to the metastatic lesion and included missense mutations with predicted functional effects in GRM3, DNMT3B, PLCG2, and SPEN. LESSONS: This report discusses the potential impact of these variants on tumor progression and metastasis, as well as the implications for identifying potential new biomarkers and therapies.

Antiplatelets and antithrombotics in neurointerventional procedures: Guideline update.

BACKGROUND: Antiplatelet and antithrombotic medication management before, during, and after neurointerventional procedures has significant practice variation. This document updates and builds upon the 2014 Society of NeuroInterventional Surgery (SNIS) Guideline 'Platelet function inhibitor and platelet function testing in neurointerventional procedures', providing updates based on the treatment of specific pathologies and for patients with specific comorbidities. METHODS: We performed a structured literature review of studies that have become available since the 2014 SNIS Guideline. We graded the quality of the evidence. Recommendations were arrived at through a consensus conference of the authors, then with additional input from the full SNIS Standards and Guidelines Committee and the SNIS Board of Directors. RESULTS: The management of antiplatelet and antithrombotic agents before, during, and after endovascular neurointerventional procedures continues to evolve. The following recommendations were agreed on. (1) It is reasonable to resume anticoagulation after a neurointerventional procedure or major bleeding episode as soon as the thrombotic risk exceeds the bleeding risk in an individual patient (Class I, Level C-EO). (2) Platelet testing can be useful to guide local practice, and specific approaches to using the numbers demonstrate marked local variability (Class IIa, Level B-NR). (3) For patients without comorbidities undergoing brain aneurysm treatment, there are no additional considerations for medication choice beyond the thrombotic risks of the catheterization procedure and aneurysm treatment devices (Class IIa, Level B-NR). (4) For patients undergoing neurointerventional brain aneurysm treatment who have had cardiac stents placed within the last 6-12 months, dual antiplatelet therapy (DAPT) is recommended (Class I, Level B-NR). (5) For patients being evaluated for neurointeventional brain aneurysm treatment who had venous thrombosis more than 3 months prior, discontinuation of oral anticoagulation (OAC) or vitamin K antagonists should be considered as weighed against the risk of delaying aneurysm treatment. For venous thrombosis less than 3 months in the past, delay of the neurointerventional procedure should be considered. If this is not possible, see atrial fibrillation recommendations (Class IIb, Level C-LD). (6) For patients with atrial fibrillation receiving OAC and in need of a neurointerventional procedure, the duration of TAT (triple antiplatelet/anticoagulation therapy=OAC plus DAPT) should be kept as short as possible or avoided in favor of OAC plus single antiplatelet therapy (SAPT) based on the individual's ischemic and bleeding risk profile (Class IIa, Level B-NR). (7) For patients with unruptured brain arteriovenous malformations there is no indication to change antiplatelet or anticoagulant management instituted for management of another disease (Class IIb, Level C-LD). (8) Patients with symptomatic intracranial atherosclerotic disease (ICAD) should continue DAPT following neurointerventional treatment for secondary stroke prevention (Class IIa, Level B-NR). (9) Following neurointerventional treatment for ICAD, DAPT should be continued for at least 3 months. In the absence of new stroke or transient ischemic attack symptoms, reversion to SAPT can be considered based on an individual patient's risk of hemorrhage versus ischemia (Class IIb, Level C-LD). (10) Patients undergoing carotid artery stenting (CAS) should receive DAPT before and for at least 3 months following their procedure (Class IIa, Level B-R). (11) In patients undergoing CAS during emergent large vessel occlusion ischemic stroke treatment, it may be reasonable to administer a loading dose of intravenous or oral glycoprotein IIb/IIIa or P2Y12 inhibitor followed by maintenance intravenous infusion or oral dosing to prevent stent thrombosis whether or not the patient has received thrombolytic therapy (Class IIb, C-LD). (12) For patients with cerebral venous sinus thrombosis, anticoagulation with heparin is front-line therapy; endovascular therapy may be considered particularly in cases of clinical deterioration despite medical therapy (Class IIa, Level B-R). CONCLUSIONS: Although the quality of evidence is lower than for coronary interventions due to a lower number of patients and procedures, neurointerventional antiplatelet and antithrombotic management shares several themes. Prospective and randomized studies are needed to strengthen the data supporting these recommendations.

DNA methylation provides diagnostic value for meningioma recurrence in clinical practice.

BACKGROUND: Meningiomas are the most common intracranial tumors. Recent advancements in the genetic profiling of tumors have allowed information including DNA copy number analysis, mutational analysis, and RNA sequencing to be more frequently reported, in turn allowing better characterization of meningiomas. In recent years, analysis of tumor methylomes that reflects both cell-origin methylation signatures and somatically acquired DNA methylation changes has been utilized to better classify meningiomas with great success. METHOD: We report DNA methylation profiling on meningiomas from 17 patients. Formalin-fixed paraffin-embedded (FFPE) meningioma tumor samples were processed, loaded onto the Infinium Methylation EPIC array, and scanned using the Illumina IScan system. Raw IDAT files were processed through the the CNS tumor classifier developed by the Molecular Neuropathology group at the German Cancer Research Center (DKFZ). Corresponding genomics were captured using targeted sequencing panels. RESULT: Among the meningioma samples, 13 samples were classified as "benign," two samples as "intermediate," and the remaining three samples (from two patients) as "malignant," based on previously validated classification algorithms. In addition to tumor methylation profiling, we also present information that includes patient demographics, clinical presentations, tumor characteristics (including size and location), surgical approaches, and mutational analysis. The two patients who provided the samples with "malignant" methylation classifications had tumor recurrence, reflecting a more aggressive disease course. CONCLUSION: In accordance with prior reports, our case series provides support that tumor DNA methylation profiling adds meaningful classification information and may be beneficial to incorporate in clinical practice. Our report also reveals that DNA methylation combined with WHO histology classification can more accurately predict tumor behavior than WHO classification alone.

Middle Meningeal Artery Embolization for Primary Treatment of a Chronic Subdural Hematoma in a Pediatric Patient: A Systematic Review of the Literature and Case Report.

BACKGROUND: Middle meningeal artery (MMA) embolization is becoming increasingly studied as a safe, effective treatment for chronic subdural hematoma (cSDH) in adults. Among pediatric patients, however, MMA embolization for cSDH has been rarely described, and the potential benefit of this approach for pediatric patients remains unknown. OBJECTIVE: To systematically review the literature and identify cases of pediatric MMA embolization for cSDH. We also report our experience with pediatric MMA embolization. METHODS: A systematic review of the literature was performed to identify cases of pediatric MMA embolization for cSDH. Inclusion criteria included English language availability and pediatric age defined as less than 18 years. A pediatric patient treated with MMA embolization was also identified at our institution. RESULTS: Five cases of pediatric MMA embolization for cSDH were identified in the literature. Two were associated with arachnoid cysts, 2 with antiplatelet/anticoagulation therapy, and 1 with abusive head trauma. There were no adverse events, and all patients demonstrated clinical and radiological improvement on follow-up. At our institution, a previously healthy 8-year-old male was found to have a right-sided acute-on-chronic SDH during a headache evaluation. A diagnostic angiogram was performed to rule out a dural arteriovenous fistula, and right-sided MMA embolization was performed concurrently. Rapid clinical and radiological improvement was observed, with complete resolution by 6 months. CONCLUSION: MMA embolization may represent a treatment option for pediatric patients with cSDH.

Pilocytic Astrocytoma Arising from the Conus Medullaris in an Adult: A Case Report.

Low-grade, sporadic, pilocytic astrocytomas (PAs) are rare spinal cord tumors diagnosed in adult patients. Their localization to the conus medullaris is exceedingly rare, having only been described in a limited number of case reports. Here, we describe a case of a 22-year-old female presenting with back pain, lower extremity weakness, hypoesthesia, and urinary incontinence. Imaging studies demonstrated a cystic lesion of the conus medullaris that was treated with subtotal resection and cyst-subarachnoid shunt placement. Final pathology report confirmed PA from the histology of surgical specimens. We discuss the current literature of conus medullaris lesions and their differential diagnosis.

Landscape of genetic variants in sporadic meningiomas captured with clinical genomics.

BACKGROUND: Meningiomas are the most common primary central nervous system tumor. Previous studies have characterized recurrent genetic alterations that can predict patient prognosis and potentially provide new avenues for therapeutic intervention. Continued efforts to characterize the genomic changes in meningioma samples can aid in the discovery of therapeutic targets and appropriate patient stratification. METHODS: We performed targeted genomic sequencing on 25 primary and 2 recurrent meningiomas using a 500-gene panel, including canonical meningioma drivers. We further detail the genomic profiles and relevant clinical findings in three cases of angiomatous meningiomas and two recurrent atypical meningiomas. RESULTS: Our approach uncovers a diverse landscape of genomic variants in meningioma samples including mutations in established meningioma-related genes NF2, AKT1, PIK3CA, and TRAF7. In addition to known meningioma drivers, we uncover variants in genes encoding other PI3K subunits, Notch/hedgehog/Wnt signaling pathway components, and chromatin regulators. We additionally identify 22 genes mutated across multiple samples. Three patients included in the study were diagnosed with angiomatous WHO grade I meningiomas, all three of which contained variants in the PI3K-AKT signaling pathway previously described to regulate tumor angiogenesis. Analysis of patient-matched primary and recurrent atypical meningiomas revealed clonal enrichment for mutations in the SWI/SNF complex subunits ARID1A and SMARCA4. CONCLUSIONS: Targeted genomics implemented in neuro-oncology care can enhance our understanding of the genetic underpinnings of central nervous system tumors, including meningiomas. These molecular signatures may be clinically useful in dictating treatment strategies and patient follow-up.

Endovascular treatment in the multimodality management of brain arteriovenous malformations: report of the Society of NeuroInterventional Surgery Standards and Guidelines Committee.

BACKGROUND: The purpose of this review is to summarize the data available for the role of angiography and embolization in the comprehensive multidisciplinary management of brain arteriovenous malformations (AVMs METHODS: We performed a structured literature review for studies examining the indications, efficacy, and outcomes for patients undergoing endovascular therapy in the context of brain AVM management. We graded the quality of the evidence. Recommendations were arrived at through a consensus conference of the authors, then with additional input from the full Society of NeuroInterventional Surgery (SNIS) Standards and Guidelines Committee and the SNIS Board of Directors. RESULTS: The multidisciplinary evaluation and treatment of brain AVMs continues to evolve. Recommendations include: (1) Digital subtraction catheter cerebral angiography (DSA)-including 2D, 3D, and reformatted cross-sectional views when appropriate-is recommended in the pre-treatment assessment of cerebral AVMs. (I, B-NR) . (2) It is recommended that endovascular embolization of cerebral arteriovenous malformations be performed in the context of a complete multidisciplinary treatment plan aiming for obliteration of the AVM and cure. (I, B-NR) . (3) Embolization of brain AVMs before surgical resection can be useful to reduce intraoperative blood loss, morbidity, and surgical complexity. (IIa, B-NR) . (4) The role of primary curative embolization of cerebral arteriovenous malformations is uncertain, particularly as compared with microsurgery and radiosurgery with or without adjunctive embolization. Further research is needed, particularly with regard to risk for AVM recurrence. (III equivocal, C-LD) . (5) Targeted embolization of high-risk features of ruptured brain AVMs may be considered to reduce the risk for recurrent hemorrhage. (IIb, C-LD) . (6) Palliative embolization may be useful to treat symptomatic AVMs in which curative therapy is otherwise not possible. (IIb, B-NR) . (7) The role of AVM embolization as an adjunct to radiosurgery is not well-established. Further research is needed. (III equivocal, C-LD) . (8) Imaging follow-up after apparent cure of brain AVMs is recommended to assess for recurrence. Although non-invasive imaging may be used for longitudinal follow-up, DSA remains the gold standard for residual or recurrent AVM detection in patients with concerning imaging and/or clinical findings. (I, C-LD) . (9) Improved national and international reporting of patients of all ages with brain AVMs, their treatments, side effects from treatment, and their long-term outcomes would enhance the ability to perform clinical trials and improve the rigor of research into this rare condition. (I, C-EO) . CONCLUSIONS: Although the quality of evidence is lower than for more common conditions subjected to multiple randomized controlled trials, endovascular therapy has an important role in the management of brain AVMs. Prospective studies are needed to strengthen the data supporting these recommendations.

Monthly triple-dose gadolinium administration: potential associations with leukopenia, hypophosphatemia, and bone marrow T1 hyperintensity.

OBJECTIVE: Monthly scanning with triple-dose gadopentetate dimeglumine has been shown to be associated with progressive increases in bone T1 hyperintensity, hypophosphatemia, and leukopenia. This study was performed to retrospectively investigate the potential associations among these phenomena. METHODS: This retrospective analysis involved patients who had received monthly triple-dose gadopentetate dimeglumine for up to 2 years as part of treatment for multiple sclerosis. Monthly magnetic resonance imaging scans of the brain (n = 67) were segmented to evaluate the signal intensity in the cranial marrow. Potential associations among the marrow T1 hyperintensity, serum phosphate concentration, and white blood cell count were examined. RESULTS: Patients in the no leukopenia group showed a statistically significant mean monthly increase in the bone marrow signal-to-noise ratio of 0.0430/month. Patients in the leukopenia group showed a mean monthly increase in the bone marrow signal-to-noise ratio of 0.0398/month, but this was not statistically significant. Patients in the hypophosphatemia group were significantly less likely to develop leukopenia than patients who had never developed hypophosphatemia. CONCLUSIONS: Although monthly administration of triple-dose gadopentetate dimeglumine over 13 months has been associated with progressive increases in leukopenia, hypophosphatemia, and T1 signal intensity of bone, this study showed an inverse relationship between leukopenia and hypophosphatemia.

Genomic sequencing of a pregnancy associated symptomatic meningioma of the diaphragma sellae: a case report.

Pregnancy-associated meningiomas have unique considerations and features regarding their pathophysiology, location, genetic profile, and neurosurgical management. These tumours have been reported to undergo rapid growth during gestation and regression post-partum, implicating a role for female sex hormones in tumour physiology. In addition, these tumours occur at a higher incidence in the skull base compared to sporadic meningiomas in the general population, often impinging neurovascular structures and requiring emergent resection. While the genomics of sporadic meningiomas have been described, there are no reports characterizing the genetic features of those associated with pregnancy. Here we describe a patient diagnosed with a diphragma sellae meningioma early in the third trimester after presenting with rapidly deteriorating vision. At 32 weeks gestation the baby was delivered by caesarean section and the tumour subsequently removed. Genomic profiling of the tumour sample revealed variants of unknown significant (VUS) in six genes, none of which were in canonical meningioma drivers. We describe our surgical approach and discuss the relevant pathology and genomics, as well as medical and surgical management considerations of meningiomas in pregnancy.

Thrombectomy in special populations: report of the Society of NeuroInterventional Surgery Standards and Guidelines Committee.

BACKGROUND: The purpose of this guideline is to summarize the data available for performing mechanical thrombectomy (MT) for emergent large vessel occlusion (ELVO) stroke in special populations not typically included in large randomized controlled clinical trials, including children, the elderly, pregnant women, patients who have recently undergone surgery, and patients with thrombocytopenia, collagen vascular disorders, and endocarditis. METHODS: We performed a literature review for studies examining the indications, efficacy, and outcomes for patients undergoing MT for ischemic stroke aged <18 years and >80 years, pregnant patients, patients who have recently undergone surgery, and those with thrombocytopenia, collagen vascular diseases, or endocarditis. We graded the quality of the evidence. RESULTS: MT can be effective for the treatment of ELVO in ischemic stroke for patients over age 80 years and under age 18 years, thrombocytopenic patients, pregnant patients, and patients with endocarditis. While outcomes are worse compared to younger patients and those with normal platelet counts (respectively), there is still a benefit in the elderly (in both mRS and mortality). Data are very limited for patients with collagen vascular diseases; although diagnostic cerebral angiography carries increased risks, MT may be appropriate in carefully selected patients in whom untreated ELVO would likely result in disabling or fatal outcome.

Single-cell multimodal glioma analyses identify epigenetic regulators of cellular plasticity and environmental stress response.

Glioma intratumoral heterogeneity enables adaptation to challenging microenvironments and contributes to therapeutic resistance. We integrated 914 single-cell DNA methylomes, 55,284 single-cell transcriptomes and bulk multi-omic profiles across 11 adult IDH mutant or IDH wild-type gliomas to delineate sources of intratumoral heterogeneity. We showed that local DNA methylation disorder is associated with cell-cell DNA methylation differences, is elevated in more aggressive tumors, links with transcriptional disruption and is altered during the environmental stress response. Glioma cells under in vitro hypoxic and irradiation stress increased local DNA methylation disorder and shifted cell states. We identified a positive association between genetic and epigenetic instability that was supported in bulk longitudinally collected DNA methylation data. Increased DNA methylation disorder associated with accelerated disease progression and recurrently selected DNA methylation changes were enriched for environmental stress response pathways. Our work identified an epigenetically facilitated adaptive stress response process and highlights the importance of epigenetic heterogeneity in shaping therapeutic outcomes.

Giant Prolactinoma Presenting With Facial Nerve Palsy and Hemiparesis.

BACKGROUND: Giant prolactinomas are an exceedingly uncommon type of pituitary adenomas that usually occur in men, and cause extremely high prolactin levels and mass-related symptoms. Rarely, patients may experience neurological deficits resembling ischemic events. METHODS: We describe an unusual case of a young man who presented with stroke-like symptoms and was found to have a giant prolactinoma. CLINICAL CASE: A 25-year-old man presented with left facial droop and gradually progressing upper and lower extremity weakness for evaluation of stroke. He reported recent weight gain and erectile dysfunction. Physical examination revealed left homonymous hemianopsia, left VII nerve palsy, and left hemiparesis. Magnetic resonance imaging of the brain showed an enormous mass in the sella turcica, which invaded the sphenoid sinus and right side of the skull base. Prolactin level was elevated at 13 580 ng/mL, and the testosterone level was low. The patient was started on cabergoline and had marked improvement in his symptoms in a few months. Fifteen months after starting treatment, he has had more than 90% reduction in tumor volume and a 93% reduction in prolactin level. CONCLUSION: Giant prolactinomas are uncommon and present with compressive symptoms that can be mistaken for a stroke. Our case is a unique report of a facial nerve palsy and hemiparesis secondary to giant prolactinoma in the absence of stroke or pituitary apoplexy.

Diaphragm Sellae Meningioma: Distinct Clinical, Anatomic, and Surgical Considerations: 2-Dimensional Operative Video.

Nestled in the parasellar region, surrounded by critical neurovascular structures, diaphragm sellae meningiomas although rare present distinct clinical, radiological, and surgical considerations.1-3 Consequently, they present surgical challenges that could be overcome with technical nuances. The origin of this meningioma on the diaphragm creates a distorted anatomy, which must be comprehended for the safe approach and resection. Three distinct subtypes of diaphragm sellae meningiomas are described, each with distinctive clinical presentations and surgical treatment implications.2 Type A originates from the upper leaf of diaphragm sellae pushing the stalk posteriorly. It usually presents with unilateral visual loss. Type B originates from the upper leaf of the diaphragm sellae pushing the stalk anteriorly. It presents with few visual symptoms, but memory disturbance and hypopituitarism are common. Type C originates from the inferior leaf of the diaphragm sellae (intrasellar meningioma) presenting with bitemporal hemianopsia and hypopituitarism. Recognizing these variations in this rare tumor subtype is critical to minimizing potential adverse outcomes associated with operative treatment. The cranial approach has been the recommended route for these lesions with an exception of the intrasellar type.1,3 In this article, we depict the pathological anatomy and demonstrate the surgical nuances in handling diaphragm sellae meningioma resection through a cranio-orbital approach4 in a patient who had an unsuccessful trans-sphenoidal resection attempt. The patient consented for the procedure. Image at 1:38 from Al-Mefty O, Operative Atlas of Meningiomas, © LWW, 1997, with permission. Image at 8:56 from Kinjo et al,2 Diaphragma sellae meningiomas, case reports, Neurosurgery, 1995, 36(6), 1082-1092, by permission of the Congress of Neurological Surgeons.