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Seeding of Infection in Previously Asymptomatic Meningioma*Edward Christopher, Fiona C Moreton, Antonia Torgersen, Peter Foley *Edward Christopher, BSc1 2; edward.christopher@; ; 07706 751203Fiona C Moreton, PhD2; fmoreton@ Antonia Torgersen, FRCPath2; a.torgersen@ Peter Foley, PhD1 2; peterfoley@ *corresponding author 1College of Medicine and Veterinary Medicine, University of Edinburgh, EH16 4TJ, UK2Department of Clinical Neurosciences, Western General Hospital, NHS Lothian, Edinburgh, EH4 2XU, UKConflict of interest: We have nothing to declare.Word count: 489Case HistoryA 75-year-old woman, who was recovering from recent episode of urosepsis, presented with three days of recurrent focal motor seizures affecting the right arm. She was aware and orientated throughout but experienced confusion and weakness after each episode. She had mild pyramidal weakness of the right arm on examination. Computed tomography (CT) head demonstrated no acute abnormality. She was started on levetiracetam. Her past medical history included type 2 diabetes, posterior circulation stroke, and known asymptomatic meningiomas at the left frontal lobe and left parietal lobe. She had no personal or family history of seizures.Her seizures became more frequent despite rapid titration of levetiracetam. Sodium valproate and phenytoin were added. Five days later, she rapidly decompensated and progressed into generalised convulsive status epilepticus, which was refractory to lorazepam, phenytoin, sodium valproate, levetiracetam, and midazolam. She was transferred to the intensive therapy unit (ITU) for intubation and ventilation. Magnetic resonance imaging (MRI) head showed a ring-enhancing cystic and exophytic component measuring 20mm in maximum diameter within the meningioma in the left frontal lobe, and extensive oedema in the subjacent white matter (Figure 1). The other meningioma remained unchanged.She underwent uncomplicated left frontal craniotomy for presumed abscess secondary to infected meningioma (meningioma abscess). The infected meningioma and its abscess were exposed and resected. The other meningioma was left intact. Histopathology demonstrated WHO Grade I meningioma with necrotic area and neutrophil polymorphs evident centrally (Figure 2). A culture of the abscess grew the same organism as the urine culture from preceding urosepsis, Escherichia coli, with strikingly similar antibiotic sensitivity profiles. She had an uneventful recovery and was started on antibiotics and continued on maintenance antiepileptic drugs postoperatively. She had residual right hemiparesis which gradually improved with physiotherapy. She was neurologically and clinically stable and remained seizure-free at three months follow up.DiscussionMeningioma is a common intracranial tumour and is mostly benign ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"Mg3aaR6o","properties":{"formattedCitation":"\\super 1\\nosupersub{}","plainCitation":"1","noteIndex":0},"citationItems":[{"id":54,"uris":[""],"uri":[""],"itemData":{"id":54,"type":"article-journal","abstract":"Evolving interest in meningioma, the most common primary brain tumor, has refined contemporary management of these tumors. Problematic, however, is the paucity of prospective clinical trials that provide an evidence-based algorithm for managing meningioma. This review summarizes the published literature regarding the treatment of newly diagnosed and recurrent meningioma, with an emphasis on outcomes stratified by WHO tumor grade. Specifically, this review focuses on patient outcomes following treatment (either adjuvant or at recurrence) with surgery or radiation therapy inclusive of radiosurgery and fractionated radiation therapy. Phase II trials for patients with meningioma have recently completed accrual within the Radiation Therapy Oncology Group and the European Organisation for Research and Treatment of Cancer consortia, and Phase III studies are being developed. However, at present, there are no completed prospective, randomized trials assessing the role of either surgery or radiation therapy. Successful completion of future studies will require a multidisciplinary effort, dissemination of the current knowledge base, improved implementation of WHO grading criteria, standardization of response criteria and other outcome end points, and concerted efforts to address weaknesses in present treatment paradigms, particularly for patients with progressive or recurrent low-grade meningioma or with high-grade meningioma. In parallel efforts, Response Assessment in Neuro-Oncology (RANO) subcommittees are developing a paper on systemic therapies for meningioma and a separate article proposing standardized end point and response criteria for meningioma.","container-title":"Journal of Neurosurgery","DOI":"10.3171/2014.7.JNS131644","ISSN":"1933-0693","issue":"1","journalAbbreviation":"J. Neurosurg.","language":"eng","note":"PMID: 25343186\nPMCID: PMC5062955","page":"4-23","source":"PubMed","title":"Meningiomas: knowledge base, treatment outcomes, and uncertainties. A RANO review","title-short":"Meningiomas","volume":"122","author":[{"family":"Rogers","given":"Leland"},{"family":"Barani","given":"Igor"},{"family":"Chamberlain","given":"Marc"},{"family":"Kaley","given":"Thomas J."},{"family":"McDermott","given":"Michael"},{"family":"Raizer","given":"Jeffrey"},{"family":"Schiff","given":"David"},{"family":"Weber","given":"Damien C."},{"family":"Wen","given":"Patrick Y."},{"family":"Vogelbaum","given":"Michael A."}],"issued":{"date-parts":[["2015",1]]}}}],"schema":""} 1. The discovery of asymptomatic meningiomas in particular is becoming more common ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"3O6M6PLt","properties":{"formattedCitation":"\\super 2\\nosupersub{}","plainCitation":"2","noteIndex":0},"citationItems":[{"id":53,"uris":[""],"uri":[""],"itemData":{"id":53,"type":"article-journal","abstract":"BackgroundIncidental discovery accounts for 30% of newly-diagnosed intracranial meningiomas. There is no consensus on their optimal management. This review aimed to evaluate the outcomes of different management strategies for these tumors.MethodsUsing established systematic review methods, six databases were scanned up to September 2017. Pooled event proportions were estimated using a random effects model. Meta-regression of prognostic factors was performed using individual patient data.ResultsTwenty studies (2130 patients) were included. Initial management strategies at diagnosis were: surgery (27.3%), stereotactic radiosurgery (22.0%) and active monitoring (50.7%) with a weighted mean follow-up of 49.5 months (SD = 29.3). The definition of meningioma growth and monitoring regimens varied widely impeding relevant meta-analysis. The pooled risk of symptom development in patients actively monitored was 8.1% (95% CI 2.7–16.1). Associated factors were peritumoral edema (OR 8.72 [95% CI 0.35–14.90]) and meningioma diameter ≥ 3 cm (OR 34.90 [95% CI 5.17–160.40]). The pooled proportion of intervention after a duration of active monitoring was 24.8% (95% CI 7.5–48.0). Weighted mean time-to-intervention was 24.8 months (SD = 18.2). The pooled risks of morbidity following surgery and radiosurgery, accounting for cross-over, were 11.8% (95% CI 3.7–23.5) and 32.0% (95% CI 10.6–70.5) respectively. The pooled proportion of operated meningioma being WHO grade I was 94.0% (95% CI 88.2–97.9).ConclusionThe management of incidental meningioma varies widely. Most patients who clinically or radiologically progressed did so within 5 years of diagnosis. Intervention at diagnosis may lead to unnecessary overtreatment. Prospective data is needed to develop a risk calculator to better inform management strategies.","container-title":"Journal of Neuro-Oncology","DOI":"10.1007/s11060-019-03104-3","ISSN":"1573-7373","journalAbbreviation":"J Neurooncol","language":"en","source":"Springer Link","title":"Incidental intracranial meningiomas: a systematic review and meta-analysis of prognostic factors and outcomes","title-short":"Incidental intracranial meningiomas","URL":"","author":[{"family":"Islim","given":"Abdurrahman I."},{"family":"Mohan","given":"Midhun"},{"family":"Moon","given":"Richard D. C."},{"family":"Srikandarajah","given":"Nisaharan"},{"family":"Mills","given":"Samantha J."},{"family":"Brodbelt","given":"Andrew R."},{"family":"Jenkinson","given":"Michael D."}],"accessed":{"date-parts":[["2019",1,31]]},"issued":{"date-parts":[["2019",1,17]]}}}],"schema":""} 2. These asymptomatic meningiomas may however predispose patients to potentially fatal risks ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"jds7l7H9","properties":{"formattedCitation":"\\super 2\\nosupersub{}","plainCitation":"2","noteIndex":0},"citationItems":[{"id":53,"uris":[""],"uri":[""],"itemData":{"id":53,"type":"article-journal","abstract":"BackgroundIncidental discovery accounts for 30% of newly-diagnosed intracranial meningiomas. There is no consensus on their optimal management. This review aimed to evaluate the outcomes of different management strategies for these tumors.MethodsUsing established systematic review methods, six databases were scanned up to September 2017. Pooled event proportions were estimated using a random effects model. Meta-regression of prognostic factors was performed using individual patient data.ResultsTwenty studies (2130 patients) were included. Initial management strategies at diagnosis were: surgery (27.3%), stereotactic radiosurgery (22.0%) and active monitoring (50.7%) with a weighted mean follow-up of 49.5 months (SD = 29.3). The definition of meningioma growth and monitoring regimens varied widely impeding relevant meta-analysis. The pooled risk of symptom development in patients actively monitored was 8.1% (95% CI 2.7–16.1). Associated factors were peritumoral edema (OR 8.72 [95% CI 0.35–14.90]) and meningioma diameter ≥ 3 cm (OR 34.90 [95% CI 5.17–160.40]). The pooled proportion of intervention after a duration of active monitoring was 24.8% (95% CI 7.5–48.0). Weighted mean time-to-intervention was 24.8 months (SD = 18.2). The pooled risks of morbidity following surgery and radiosurgery, accounting for cross-over, were 11.8% (95% CI 3.7–23.5) and 32.0% (95% CI 10.6–70.5) respectively. The pooled proportion of operated meningioma being WHO grade I was 94.0% (95% CI 88.2–97.9).ConclusionThe management of incidental meningioma varies widely. Most patients who clinically or radiologically progressed did so within 5 years of diagnosis. Intervention at diagnosis may lead to unnecessary overtreatment. Prospective data is needed to develop a risk calculator to better inform management strategies.","container-title":"Journal of Neuro-Oncology","DOI":"10.1007/s11060-019-03104-3","ISSN":"1573-7373","journalAbbreviation":"J Neurooncol","language":"en","source":"Springer Link","title":"Incidental intracranial meningiomas: a systematic review and meta-analysis of prognostic factors and outcomes","title-short":"Incidental intracranial meningiomas","URL":"","author":[{"family":"Islim","given":"Abdurrahman I."},{"family":"Mohan","given":"Midhun"},{"family":"Moon","given":"Richard D. C."},{"family":"Srikandarajah","given":"Nisaharan"},{"family":"Mills","given":"Samantha J."},{"family":"Brodbelt","given":"Andrew R."},{"family":"Jenkinson","given":"Michael D."}],"accessed":{"date-parts":[["2019",1,31]]},"issued":{"date-parts":[["2019",1,17]]}}}],"schema":""} 2. Its rich vascularity and increased cerebrovascular permeability from the destruction of blood-brain-barrier confer meningioma susceptibility to infection, particularly if infection is present elsewhere in the body ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"zmi1Hyjw","properties":{"formattedCitation":"\\super 3\\nosupersub{}","plainCitation":"3","noteIndex":0},"citationItems":[{"id":18,"uris":[""],"uri":[""],"itemData":{"id":18,"type":"article-journal","abstract":"Objective\nInfection associated with an intracranial meningioma is an extremely rare condition. Only six cases have been described in the literature. Because of its dual pathologies, initial radiologic diagnosis can be difficult. We present the first reported case of multiple infected intracranial meningiomas and correlate the radiologic and histologic findings.\nMethods\nA 70-year-old woman presented with sepsis and a left hemiparesis following ureteroscopy and lithotripsy. A large right parietal lesion and a smaller left frontal lesion were diagnosed on magnetic resonance imaging. Diffusion-weighted imaging and an apparent diffusion coefficient map demonstrated features of cerebral metastases.\nResults\nA 2-stage excision confirmed atypical meningiomas containing an intratumoral abscess secondary to Escherichia coli. The patient made a full neurologic recovery. Despite the additional techniques, the radiologic diagnosis was initially challenging because of the dual pathologies. Nonetheless, the radiologic appearance was consistent with the complex histologic findings.\nConclusions\nIn the appropriate clinical context, diffusion-weighted imaging and apparent diffusion coefficient map aid the diagnosis of infected intracranial meningiomas.","container-title":"World Neurosurgery","DOI":"10.1016/j.wneu.2013.07.081","ISSN":"1878-8750","issue":"3","journalAbbreviation":"World Neurosurgery","page":"651.e9-651.e13","source":"ScienceDirect","title":"Infected Intracranial Meningiomas","volume":"81","author":[{"family":"Lo","given":"William B."},{"family":"Cahill","given":"Julian"},{"family":"Carey","given":"Martyn"},{"family":"Mehta","given":"Hiten"},{"family":"Shad","given":"Amjad"}],"issued":{"date-parts":[["2014",3,1]]}}}],"schema":""} 3. The meningioma abscess in our patient developed rapidly and grew the same organism as the urine culture from the preceding urosepsis. Coupled with the evolution of events, this is strongly suggestive of haematogenous seeding of infection. The preferential seeding of infection in one but not both meningiomas in our case may well reflect the vascular heterogeneity between the two meningiomas. The meningioma abscess likely acted as the seizure trigger, given the compatibility of the clinical semiology with the lesion location and clinical improvement following definitive abscess treatment. Meningioma abscess is an important complication for clinicians to recognise, especially in patients with known meningioma in the context of systemic infection. This is especially relevant in modern neurological practice, where the growth in accessibility and use of neuroimaging makes the incidental discovery of asymptomatic meningiomas and their conservative management fairly common ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"fn6CuvYD","properties":{"formattedCitation":"\\super 4\\nosupersub{}","plainCitation":"4","noteIndex":0},"citationItems":[{"id":42,"uris":[""],"uri":[""],"itemData":{"id":42,"type":"article-journal","abstract":"With the increasing availability and use of modern brain diagnostic imaging modalities, discovery of incidental meningiomas has become fairly common. This creates a dilemma among neurosurgeons as to whether these lesions should be treated. Numerous natural history studies have been published in an effort to shed light on the potential for growth of incidental meningiomas. The available data appear to suggest that these tumors can fall into 1 of 3 main growth patterns: no growth, linear growth, or exponential growth. The therapeutic strategy selected should also consider several other factors, mainly the risk of complications from an eventual surgery, the possibility of malignancies and other pathological conditions that mimic meningiomas, and the age and medical condition of the patient. The authors believe that most asymptomatic incidental meningiomas can be observed using serial imaging and clinical follow-up evaluations. Surgical interventions are typically reserved for large, symptomatic lesions and those with documented potential for significant growth.","container-title":"Neurosurgical Focus","DOI":"10.3171/2011.9.FOCUS11220","ISSN":"1092-0684","issue":"6","journalAbbreviation":"Neurosurg Focus","language":"eng","note":"PMID: 22133182","page":"E19","source":"PubMed","title":"Incidental meningiomas","volume":"31","author":[{"family":"Chamoun","given":"Roukoz"},{"family":"Krisht","given":"Khaled M."},{"family":"Couldwell","given":"William T."}],"issued":{"date-parts":[["2011",12]]}}}],"schema":""} 4. The elderly and potentially immunosuppressed are a rapidly growing patient group which, as our case demonstrates, is particularly at risk of abscess development ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"DJxNZYpX","properties":{"formattedCitation":"\\super 5\\nosupersub{}","plainCitation":"5","noteIndex":0},"citationItems":[{"id":44,"uris":[""],"uri":[""],"itemData":{"id":44,"type":"article-journal","abstract":"Significant advances in the diagnosis and management of bacterial brain abscess over the past several decades have improved the expected outcome of a disease once regarded as invariably fatal. Despite this, intraparenchymal abscess continues to present a serious and potentially life-threatening condition. Brain abscess may result from traumatic brain injury, prior neurosurgical procedure, contiguous spread from a local source, or hematogenous spread of a systemic infection. In a significant proportion of cases, an etiology cannot be identified. Clinical presentation is highly variable and routine laboratory testing lacks sensitivity. As such, a high degree of clinical suspicion is necessary for prompt diagnosis and intervention. Computed tomography and magnetic resonance imaging offer a timely and sensitive method of assessing for abscess. Appearance of abscess on routine imaging lacks specificity and will not spare biopsy in cases where the clinical context does not unequivocally indicate infectious etiology. Current work with advanced imaging modalities may yield more accurate methods of differentiation of mass lesions in the brain. Management of abscess demands a multimodal approach. Surgical intervention and medical therapy are necessary in most cases. Prognosis of brain abscess has improved significantly in the recent decades although close follow-up is required, given the potential for long-term sequelae and a risk of recurrence.","container-title":"The Neurohospitalist","DOI":"10.1177/1941874414540684","ISSN":"1941-8744","issue":"4","journalAbbreviation":"Neurohospitalist","language":"eng","note":"PMID: 25360205\nPMCID: PMC4212419","page":"196-204","source":"PubMed","title":"Bacterial brain abscess","volume":"4","author":[{"family":"Patel","given":"Kevin"},{"family":"Clifford","given":"David B."}],"issued":{"date-parts":[["2014",10]]}}}],"schema":""} 5. Setting low thresholds for definitive imaging could lead to early detection of this potentially fatal yet highly treatable condition.Key practical messagesConsider the possibility of meningioma abscess in patients with meningioma and neurological deterioration occurring in the context of infectionConsider MRI in cases of uncertainty, even when CT brain has been unrevealingAcknowledgments We thank the patient for granting permission to publish this information.References ADDIN ZOTERO_BIBL {"uncited":[],"omitted":[],"custom":[]} CSL_BIBLIOGRAPHY 1. Rogers L, Barani I, Chamberlain M, et al. Meningiomas: knowledge base, treatment outcomes, and uncertainties. A RANO review. J Neurosurg. 2015;122(1):4-23. doi:10.3171/2014.7.JNS1316442. Islim AI, Mohan M, Moon RDC, et al. Incidental intracranial meningiomas: a systematic review and meta-analysis of prognostic factors and outcomes. J Neurooncol. January 2019. doi:10.1007/s11060-019-03104-33. Lo WB, Cahill J, Carey M, Mehta H, Shad A. Infected Intracranial Meningiomas. World Neurosurgery. 2014;81(3):651.e9-651.e13. doi:10.1016/j.wneu.2013.07.0814. Chamoun R, Krisht KM, Couldwell WT. Incidental meningiomas. Neurosurg Focus. 2011;31(6):E19. doi:10.3171/2011.9.FOCUS112205. Patel K, Clifford DB. Bacterial brain abscess. Neurohospitalist. 2014;4(4):196-204. doi:10.1177/1941874414540684Figure LegendsFigure 1. Neuroimaging scans of the patient.Pre-operative T1-weighted gadolinium-enhanced (A) and T2-weighted gadolinium-enhanced (B) MRI demonstrating the development of ring-enhancing cystic and exophytic components within the left frontal lobe meningioma. Pre-operative fluid-attenuated inversion recovery MRI (C) demonstrating extensive oedema in the subjacent white matter. T1-weighted gadolinium-enhanced MRI (D) demonstrating the indolent meningioma left intact post-operatively.Figure 2. Histopathological examination of the meningioma abscess.Haematoxylin and eosin (H&E)-stained section at 4x (A) demonstrating abscess with the surrounding meningioma rim. H&E-stained section at 20x (B) demonstrating neutrophil polymorphs within the abscess with an entrapped psammoma body. H&E-stained section at 20x (C) demonstrating typical meningothelial cells on the abscess rim. Histopathology demonstrated WHO Grade I meningioma. ................
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