今日の臨床サポート 今日の臨床サポート

著者: 橋本直哉 京都府立医科大学 大学院医学研究科 脳神経外科

監修: 甲村英二 公立学校共済組合 近畿中央病院

著者校正/監修レビュー済:2024/03/06
参考ガイドライン:
  1. 脳ドックのガイドライン2019改訂委員会編:脳ドックのガイドライン2019
患者向け説明資料

改訂のポイント:
  1. 臨床での重要ポイントについて「概要・推奨」にまとめ、実臨床に役立つように改訂、推奨度・エビデンスレベルを追加した。
  1. 髄膜腫の病理分類としてWHOの脳腫瘍分類2016年版および2021年版も参考にして図表も含めて更新した。ただし、記載の増えた分子遺伝学的分類については実臨床に導入し難いため、本稿には記載を控えた。
  1. 治療の項目に新規抗てんかん薬としてラコサミド(ビムパット)を追加した。
  1. 髄膜腫の自然歴について前版以降のエビデンスレベルの高い文献を追加し、以下について新たに記載した。
  1. 2020年のメタアナリシスでは、989症例の解析で約2/3の症例が体積増加を示したが、4~5年で増大しなくなり、46例(4.7%)のみが症候化した。年間の体積変化が2.1 cm3より大きいものは症候化しやすいとされた(Nakasu S, et al. Neurol Med Chir (Tokyo). 2020 Mar 15;60(3):109-120.)。同じく2020年の報告では55カ月の追跡で441例中44例のみが増大したが、4~5年の追跡で増大しなくなるとされた(Islim AI, et al. Neuro Oncol. 2020 Feb 20;22(2):278-289.)。

概要・推奨   

  1. 頭痛などの訴えや神経学的所見から速やかに造影MRIによる診断を行う(推奨度1)
  1. 症候性髄膜腫は治療適応であり、年齢・部位・症状・腫瘍サイズ等から総合的に手術適応の有無を決定する(推奨度1)
  1. 症候性髄膜腫で手術適応がない場合は何らかの放射線治療(定位照射を含む)を選択する(推奨度1)。ただし、軽微な症状、高齢者、合併症など種々の理由による総合的判断により治療を行わない場合は、経過観察を行う(推奨度2)
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病態・疫学・診察 

疾患情報(疫学・病態)  
  1. 髄膜腫は髄膜皮細胞(meningothelial cell)(クモ膜細胞 arachnoid cell)から発生する腫瘍で、頻度が高く、多くは良性であるが悪性のものもあり、臨床的に重要な腫瘍群である。
  1. 日本の全国脳腫瘍統計(2005~2008年)[1]によると、原発性脳腫瘍のなかで最も頻度の高い腫瘍で、23.8%を占める(o:観察研究)。
  1. 男性:女性は29.9%:70.1%で女性に多い。成人に好発する腫瘍であり、ピークは50~60歳台である。15歳未満の小児例は少ない(o)。
  1. 頭蓋および脊椎の硬膜、いずれからも発生するが、好発部位は円蓋部、傍矢状洞、蝶形骨縁、大脳鎌の順である。
  1. 発生部位ごとの局所神経症状(巣症状)、頭蓋内内圧亢進症状と症候性てんかんが主な症状である。
  1. 画像診断の進歩により無症状で発見される機会が増加している(無症候性髄膜腫)。
  1. 一般人口における頻度は0.9%から2.3%と報告されており(疫学および剖検データ)、人口の1~2%は無症候性髄膜腫を有すると考えられる[2][3](o)。
 
  1. 髄膜腫の好発部位と発生の危険因子:
  1. 髄膜腫は髄膜皮細胞の存在するいずれの部位からも発生するが、好発部位がある。また、発生の危険因子が指摘されている。
  1. 髄膜腫の好発部位は、円蓋部が最も多く24.4%とおおよそ1/4を占める。次いで、傍矢状洞(11.4%)、蝶形骨縁(11.0%)、大脳鎌(9.8%)が多く、後頭蓋窩では小脳橋角部(8.2%)、斜台/錐体斜台部(6.0%)小脳テント(5.3%)が多い。脳室内(2.0%)や大孔部(1.4%)の頻度は低く、頭蓋脊椎管外の発生もまれにあり皮膚からの発生が多い(o)。
  1. 発生の危険因子としては放射線照射が(放射線誘発腫瘍)がよく知られている[4]。電磁波との明確な関連は未だ示されていない。女性に発生が多いことから、女性ホルモンの関与が注目されている。プロゲステロン受容体(PR)は48~88%で、エストロゲン受容体(ER)は5~33%で陽性であるとされている[5][6][7][8](o)。
 
髄膜腫の好発部位 (日本脳腫瘍統計2005~2008)

髄膜腫の好発部位とその頻度。

出典

Brain Tumor Registry of Japan (2005-2008).
Neurol Med Chir (Tokyo). 2017;57(Supplement-1):9-102. doi: 10.2176/nmc.sup.2017-0001.
Abstract/Text
PMID 28420810
 
  1. 髄膜腫の発生部位と症状1:
  1. 円蓋部は広大なため、発生部位によってその局所神経症状(巣症状)は異なるが、てんかん発作や頭蓋内圧亢進症状はほかの部位と同様である。
  1. 傍矢状洞髄膜腫の場合、前、中1/3に発生したものでは運動野に近く、Jackson型で始まるけいれん発作の頻度が高い。前1/3に発生した場合には、前頭葉症状としての行動異常、人格障害が多いとされる。
  1. 大脳鎌髄膜腫では、傍矢状洞の場合と似ているが、比較的下肢の麻痺が強い傾向にある。
  1. 蝶形骨縁に沿って発生した髄膜腫は、内側から外側に1/3ずつ発生母地を分割して分類されている。外側に発生したものは、板状の発育を示すことが多く、骨肥厚による眼球突出や視力障害が認められる。
  1. 一方、蝶形骨縁内側、特に前床突起部に発生したものは、視神経の圧排による視力視野障害が特徴的である。
  1. 嗅溝部/蝶形骨平面から発生した髄膜腫では、古典期にはFoster-Kennedy症候群が有名であるが実際にはまれで、嗅覚脱失に加えて前頭葉症状としての精神症状などが多い。後方へ進展すれば視力障害が出現する。
  1. 鞍結節部髄膜腫は、鞍結節部あるいは鞍隔膜から発生し視神経を下方から圧排し、高率に視神経管内へ浸潤するため、左右差のある視力視野障害を来すことが多い。
 
  1. 髄膜腫の発生部位と症状2:
  1. 脈絡叢に随伴する髄膜組織から発生する脳室内髄膜腫は、2%程度の発生頻度であるが、そのうち側脳室内に77.8%、第3脳室内に15.6%、第4脳室内に6.6%が発生すると報告されている[9](o)。
  1. 側脳室内髄膜腫では、頭蓋内圧亢進症状に加え、脳室周囲を走行する視放線障害による視野欠損が最も多い。第3脳室内髄膜腫は前半部に多く発生し、この場合は頭蓋内圧亢進症状に加えて精神障害、内分泌障害を伴う。後半部に発生した場合は眼球運動障害を来すことがある。
  1. 海綿静脈洞部髄膜腫では同部位を走行するさまざまな脳神経が障害され、動眼神経麻痺、滑車神経麻痺、三叉神経障害、外転神経麻痺を来し、自覚的には複視を訴える。
  1. 小脳橋角部髄膜腫では耳鳴、難聴、眩暈、三叉神経障害が多くみられるが、内耳道前方型では三叉神経から下位脳神経までの障害が、後方型では小脳症状が前景に立つ。
  1. テント髄膜腫は発生部位により異なるが、全体としては小脳圧排や頭蓋内圧亢進による頭痛、ふらつき、歩行障害、意識障害などが多い。
  1. 小脳半球円蓋部に発生した場合は、水頭症に加え小脳の圧排による平衡障害をみる。
 
  1. 髄膜腫の発生部位と症状3:
  1. メッケル腔から頚静脈孔の線より内側で斜台上部2/3にある髄膜腫を錐体斜台部髄膜腫と呼び、脳神経障害を高率に来す。三叉神経障害、聴神経障害が最も多く、そのほか頭痛、歩行障害、小脳症状も多い。
  1. 大孔部髄膜腫は診断が困難な腫瘍として知られているが、症状も多彩である。後頚部を含む四肢の感覚障害が自覚症状の主体であり、上肢を中心とした不規則な麻痺が出現する。解離性感覚障害、副神経麻痺、C2領域の痛覚低下などが特徴である。
  1. 頚静脈孔髄膜腫はまれな腫瘍であるが、難聴、嗄声、ふらつき、嚥下障害が多い[10](o)。
問診・診察のポイント  
  1. 頭痛などの訴えや神経学的所見から速やかにMRIかCTによる画像診断を行う。

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最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
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文献 

Brain Tumor Registry of Japan (2005-2008).
Neurol Med Chir (Tokyo). 2017;57(Supplement-1):9-102. doi: 10.2176/nmc.sup.2017-0001.
Abstract/Text
PMID 28420810
Meike W Vernooij, M Arfan Ikram, Hervé L Tanghe, Arnaud J P E Vincent, Albert Hofman, Gabriel P Krestin, Wiro J Niessen, Monique M B Breteler, Aad van der Lugt
Incidental findings on brain MRI in the general population.
N Engl J Med. 2007 Nov 1;357(18):1821-8. doi: 10.1056/NEJMoa070972.
Abstract/Text BACKGROUND: Magnetic resonance imaging (MRI) of the brain is increasingly used both in research and in clinical medicine, and scanner hardware and MRI sequences are continually being improved. These advances are likely to result in the detection of unexpected, asymptomatic brain abnormalities, such as brain tumors, aneurysms, and subclinical vascular pathologic changes. We conducted a study to determine the prevalence of such incidental brain findings in the general population.
METHODS: The subjects were 2000 persons (mean age, 63.3 years; range, 45.7 to 96.7) from the population-based Rotterdam Study in whom high-resolution, structural brain MRI (1.5 T) was performed according to a standardized protocol. Two trained reviewers recorded all brain abnormalities, including asymptomatic brain infarcts. The volume of white-matter lesions was quantified in milliliters with the use of automated postprocessing techniques. Two experienced neuroradiologists reviewed all incidental findings. All diagnoses were based on MRI findings, and additional histologic confirmation was not obtained.
RESULTS: Asymptomatic brain infarcts were present in 145 persons (7.2%). Among findings other than infarcts, cerebral aneurysms (1.8%) and benign primary tumors (1.6%), mainly meningiomas, were the most frequent. The prevalence of asymptomatic brain infarcts and meningiomas increased with age, as did the volume of white-matter lesions, whereas aneurysms showed no age-related increase in prevalence.
CONCLUSIONS: Incidental brain findings on MRI, including subclinical vascular pathologic changes, are common in the general population. The most frequent are brain infarcts, followed by cerebral aneurysms and benign primary tumors. Information on the natural course of these lesions is needed to inform clinical management.

Copyright 2007 Massachusetts Medical Society.
PMID 17978290
S Nakasu, A Hirano, T Shimura, J F Llena
Incidental meningiomas in autopsy study.
Surg Neurol. 1987 Apr;27(4):319-22. doi: 10.1016/0090-3019(87)90005-x.
Abstract/Text Two hundred thirty-one cases of incidental meningiomas found at autopsy at the Montefiore Medical Center during the period from 1950 to 1982 were reviewed. The prevalence of incidental meningiomas increased with age, and was highest in people 80 years of age or older. The male to female ratio was 1 to 3. The relative size of the tumors also increased with age. Multiple meningiomas were found in 8.2% of the cases; none of them had stigmata of neurofibromatosis.

PMID 3824137
Siegal Sadetzki, Pazit Flint-Richter, Tehila Ben-Tal, Dvora Nass
Radiation-induced meningioma: a descriptive study of 253 cases.
J Neurosurg. 2002 Nov;97(5):1078-82. doi: 10.3171/jns.2002.97.5.1078.
Abstract/Text OBJECT: Ionizing radiation is the only established risk factor recognized today in the causation of meningioma. The aim of the present report is to describe the demographic and clinical characteristics of a large series of 253 patients with radiation-induced meningiomas (RIMs). These parameters were compared with those of 41 patients with meningiomas in whom there was no previous history of irradiation (non-RIM group) and with other series of patients presented in the literature.
METHODS: The cases of RIM were recruited from a cohort of approximately 11,000 individuals who had been treated with ionizing radiation during childhood for tinea capitis and from a group of individuals who, as adults, applied for compensation because of that treatment. The non-RIM group was identified through the Israeli Cancer Registry. Exposure to radiation was carefully validated among all cases of RIM and absence of previous irradiation was verified for all patients in the non-RIM group. Significantly, a lower patient age at diagnosis, higher prevalence of calvarial tumors, higher proportion of multiple meningiomas, and a nonsignificant higher recurrence rate were observed among patients with RIM compared with the non-RIM group. The mean latency period from date of radiation exposure to development of a meningioma among the RIM group was approximately 36 years.
CONCLUSIONS: The findings of this study agree with those of other studies indicating the demographic, clinical, and even genetic variability between RIM and non-RIM cases. The existence of two different subtypes of meningiomas may have profound implications for screening, early diagnosis, and therapy of meningiomas.

PMID 12450029
Patricia Guevara, Elizabeth Escobar-Arriaga, David Saavedra-Perez, Abelardo Martinez-Rumayor, Diana Flores-Estrada, Daniel Rembao, Alejandra Calderon, Julio Sotelo, Oscar Arrieta
Angiogenesis and expression of estrogen and progesterone receptors as predictive factors for recurrence of meningioma.
J Neurooncol. 2010 Jul;98(3):379-84. doi: 10.1007/s11060-009-0086-z. Epub 2009 Dec 15.
Abstract/Text Meningiomas are benign tumors, with low rate of recurrence after surgery. The most important factor predicting recurrence is the extent of surgical resection; other factors have been studied with conflicting results. Angiogenesis, an important substratum for growth and spread of neoplasic cells, and the expression of estrogen and progesterone receptors (ER, PR), could play a role in the recurrence of meningioma. We evaluated 42 patients with meningioma diagnosis (confirmed by histopathology) treated exclusively by surgery between January 1995 and December 1999, and compared the recurring and non-recurring groups after a ten-year follow-up period. Recurrence was associated with several factors including vascular density (VD), cell proliferation index (CPI), ER, PR, and cyclin E (CE) tissue expression, as evaluated by immunohistochemistry. Complete surgical resection was achieved in 41% of patients. Recurrence of meningioma was found in 17 patients (40%). Median + or - standard deviation (SD) of recurrence time was 32 + or - 5 months. When recurrence versus no recurrence was compared, mean + or - SD of VD and CPI were 9 + or - 3.6 and 607.6 + or - 233 (40x/10 fields) respectively. Tissue expression was positive for ER, PR, and CE in 28, 62 and 91% of patients, respectively. The sole significant recurrence-associated factors were extent of resection (P = 0.003) and VD (P = 0.004). ER, PR, and CE-tissue expression were not statistically significant. The most important factor associated with meningioma relapse was vascular density, independently of hormonal status and extent of surgical resection. Patients with a high risk of recurrence could benefit from additional treatment.

PMID 20013146
Katariina Korhonen, Tiina Salminen, Jani Raitanen, Anssi Auvinen, Jorma Isola, Hannu Haapasalo
Female predominance in meningiomas can not be explained by differences in progesterone, estrogen, or androgen receptor expression.
J Neurooncol. 2006 Oct;80(1):1-7. doi: 10.1007/s11060-006-9146-9. Epub 2006 May 13.
Abstract/Text The female predominance in meningioma incidence and association between meningioma and breast cancer suggest that growth of meningiomas is hormone-dependent. There are several discrepancies in literature about the proliferative effect of sex hormones on meningiomas. This study aims to evaluate the hormone receptor status of meningiomas and assess its relation to age, sex, histological grade, recurrence, and proliferation activity. The material was based on consecutive patients operated for meningioma at Tampere University Hospital in 1989-1999. The occurrence of progesterone, estrogen and androgen receptor in patients with primary and recurrent meningiomas was studied immunohistochemically by using specific monoclonal antibodies. Hormonal status was determined in 510 tumor samples. 443 samples were from primary meningiomas and 67 from recurrent tumors. Of the samples, 455 were benign (WHO grade I), 49 atypical (grade II), and 6 malignant (grade III). Of the primary tumor samples, 88% were progesterone receptor positive, 40% were positive for estrogen and 39% for androgen receptors. Grade I meningiomas had significantly higher incidence for estrogen and androgen receptors than higher grade meningiomas. Estrogen positive tumor samples had significantly higher proliferation index than estrogen negative samples. No difference in expression of sex hormone receptors was observed by sexes or age group. Estrogen and androgen receptors may have more influence on the pathogenesis of meningiomas than earlier thought. The higher incidence of meningiomas in women can not be explained by differences of sex hormone receptor expression.

PMID 16703453
Svetlana Pravdenkova, Ossama Al-Mefty, Jeffrey Sawyer, Muhammad Husain
Progesterone and estrogen receptors: opposing prognostic indicators in meningiomas.
J Neurosurg. 2006 Aug;105(2):163-73. doi: 10.3171/jns.2006.105.2.163.
Abstract/Text OBJECT: The preponderance of progesterone receptors (PRs) and the scarcity of estrogen receptors (ERs) in meningiomas are well known. The expression of PRs may relate to tumor grade and recurrence. Cytogenetic abnormalities are associated with aggressive behavior, recurrence, and progression. In this study, the authors focus on the prognostic implications of hormone receptors in meningiomas to help determine the clinical and biological aggressiveness of tumors and their correlations with cytogenetic abnormalities.
METHODS: Two hundred thirty-nine patients with meningiomas were separated into three groups. Group 1 (PR-positive group) comprised patients whose meningiomas displayed expression of PRs alone. Group 2 (receptor-negative group) included patients whose lesions did not have receptors for either progesterone or estrogen. Group 3 (ER-positive group) included patients whose tumors displayed expression of ERs. Clinical and histological findings, proliferative indices, tumor recurrence, and cytogenetic findings were analyzed by performing the Fisher exact test. Compared with the receptor-negative (Group 2) and ER-positive (Group 3) groups, the PR-positive group (Group 1) had a statistically significant lower proliferative index and a smaller number of patients in whom there were aggressive histopathological findings or changes in karyotype. In Groups 1, 2, and 3, the percentages of cases with aggressive histopathological findings were 10, 31, and 33%, respectively; the percentages of cases with chromosomal abnormalities were 50, 84, and 86%, respectively; and the percentages of cases in which there initially was no residual tumor but recurrence was documented were 5, 30, and 27%, respectively. A statistically significant increase in the involvement of chromosomes 14 and 22 was identified in receptor-negative and ER-positive de novo meningiomas, when compared with the PR-positive group. Abnormalities on chromosome 19 were statistically significantly higher in receptor-negative meningiomas than in PR-positive tumors.
CONCLUSIONS: The expression of the PR alone in meningiomas signals a favorable clinical and biological outcome. A lack of receptors or the presence of ERs in meningiomas correlates with an accumulation of qualitative and quantitative karyotype abnormalities, a higher proportional involvement of chromosomes 14 and 22 in de novo tumors, and an increasing potential for aggressive clinical behavior, progression, and recurrence of these lesions. Sex hormone receptor status should routinely be studied for its prognostic value, especially in female patients, and should be taken into account in tumor grading. The initial receptor status of a tumor may change in progression or recurrence of tumor.

PMID 17219818
F Roser, M Nakamura, M Bellinzona, S K Rosahl, H Ostertag, M Samii
The prognostic value of progesterone receptor status in meningiomas.
J Clin Pathol. 2004 Oct;57(10):1033-7. doi: 10.1136/jcp.2004.018333.
Abstract/Text BACKGROUND: Meningiomas are known to recur frequently, and their longterm management remains controversial. Previous studies indicate that progesterone and its receptors can play a role in the recurrence of meningiomas, but the correlation between the presence of these receptors and patients' outcome is unclear.
AIM: To conduct a retrospective analysis to investigate the prognostic relevance of progesterone receptor (PR) expression in meningiomas.
METHODS: Five hundred and eighty eight meningiomas operated on over a period of 10 years were examined immunohistochemically to determine the PR status using monoclonal antibodies. Several factors including recurrence (mean follow up of 65 month), sex, tumour tissue consistency, location, vascularity, and en plaque appearance were analysed.
RESULTS: PR status showed comparable values for men and women. World Health Organisation (WHO) grade II and III tumours had significantly fewer receptors than benign meningiomas. There was no significant correlation between PR status and recurrence rates in WHO grade I totally removed meningiomas. However, a combination of PR status and proliferation indices was shown to predict recurrence reliably.
CONCLUSIONS: Together with routine histological evaluation, PR status can help to describe the biological behaviour of meningiomas. Only a combination of clinical and biological features can describe the behaviour of meningiomas, predict their recurrence, and help to devise more effective follow up strategies.

PMID 15452155
Makoto Nakamura, Florian Roser, Melena Struck, Peter Vorkapic, Madjid Samii
Tuberculum sellae meningiomas: clinical outcome considering different surgical approaches.
Neurosurgery. 2006 Nov;59(5):1019-28; discussion 1028-9. doi: 10.1227/01.NEU.0000245600.92322.06.
Abstract/Text OBJECTIVE: Tuberculum sellae meningiomas present a special challenge because of their proximity to arteries of the anterior circulation, anterior visual pathways, and the hypothalamus. The authors report on the clinical outcome after surgical treatment of tuberculum sellae meningiomas in our neurosurgical department.
METHODS: A retrospective study was conducted analyzing the charts of the patients, including surgical records, discharge letters, histological records, follow-up records, and imaging studies. Patients with associated neurofibromatosis Type 2 were excluded from the study.
RESULTS: One thousand eight hundred meningiomas were operated on between 1978 and 2002. Seventy-two of these patients had tuberculum sellae meningiomas; four had undergone previous surgical procedures in outside hospitals. Fifty-five patients were women; 17 were men. Their mean age was 54.3 years (range, 30-86 yr). All patients had visual disturbances at presentation. Tumors were operated through the bifrontal approach (n = 21, from 1978 through 1995), the pterional/frontotemporal approach (n = 21, from 1982 through 2002), and the frontolateral approach (n = 30, from 1984 through 2002). Total tumor removal was achieved in most patients (Simpson 1 + 2, 91.7%). The perioperative mortality rate was 2.8% (two out of 72 patients). Immediate postoperative improvement of visual disturbance was observed in 65% of patients. Visual improvement was dependent on the duration of preoperative visual symptoms, but not on preoperative visual acuity or tumor size. The visual improvement rate was significantly better in patients who underwent frontolateral tumor resection (77.8%) compared with those who underwent bifrontal craniotomy (46.2%). The overall recurrence rate was 2.8% (two out of 72 patients). The mean follow-up time for all patients was 4 to 238 months (mean, 45.3 mo [3.8 yr]).
CONCLUSION: From 1978 through 2002, tuberculum sellae meningiomas were removed microsurgically using three different surgical approaches. Considering the operative morbidity and mortality, the frontolateral and pterional approach provided remarkable improvement compared with the bifrontal approach. These approaches allowed quick access to the tumor and were minimally invasive with less brain exposure, but still engendered high rates of total tumor removal. By comparison, the frontolateral approach provided the best results concerning visual outcome while representing the least invasive surgical approach.

PMID 17143236
Mario Sanna, Andrea Bacciu, Maurizio Falcioni, Abdelkader Taibah, Paolo Piazza
Surgical management of jugular foramen meningiomas: a series of 13 cases and review of the literature.
Laryngoscope. 2007 Oct;117(10):1710-9. doi: 10.1097/MLG.0b013e3180cc20a3.
Abstract/Text OBJECTIVE: Primary meningiomas occurring within the jugular foramen are exceedingly rare lesions presumed to originate from arachnoid-lining cells situated within the jugular foramen. The objective of this study is to analyze the management and outcome in a series of 13 primary jugular foramen meningiomas collected at a single center.
STUDY DESIGN: Retrospective study.
SETTING: Quaternary referral otology and skull base private center.
METHODS: Charts belonging to 13 consecutive patients with pathologically confirmed jugular foramen meningioma surgically treated between September 1991 and May 2005 were examined retrospectively. The follow-up of the series ranged from 12 to 120 (mean, 42.8 +/- 27.5) months.
RESULTS: Four (28.5%) patients underwent single-stage tumor removal through the petro-occipital transigmoid (POTS) approach. In two patients with preoperative unserviceable hearing, a combined POTS-translabyrinthine approach was adopted. Two patients underwent a combined POTS-transotic approach because of massive erosion of the carotid canal. A modified transcochlear approach type D with posterior rerouting of the facial nerve and transection of the sigmoid sinus and jugular bulb was performed in two patients with a huge cerebellopontine angle tumor component with extension to the prepontine cistern together with massive involvement of the petrous bone and middle ear and encasement of the vertical and horizontal segments of the intrapetrous carotid artery. In one patient with evidence of a dominant sinus on the site of the tumor, a subtotal tumor removal via an enlarged translabyrinthine approach (ETLA) was planned to resect the intradural component of the tumor. Two patients in our series underwent a planned staged procedure on account of a huge tumor component in the neck. One of these patients underwent a first-stage infratemporal fossa approach type A to remove the tumor component in the neck; the second-stage intradural removal of the tumor was accomplished via an ETLA. The last patient underwent a first-stage modified transcochlear type D approach to remove the intradural tumor component followed by a second-stage transcervical procedure for removal of the extracranial component. Gross total tumor removal (Simpson grade I-II) was achieved in 11 (84.6%) cases. Subtotal removal of the tumor was accomplished in two patients. Good facial nerve function (grades I and II) was achieved in 46.1% of cases, whereas acceptable function (grade III) was achieved in the remaining cases 1 year after tumor removal. Hearing was preserved at the preoperative level in all four patients who underwent surgery via the POTS approach. After surgery, no patient recovered function of the preoperatively paralyzed lower cranial nerves. A new deficit of one or more of the lower cranial nerves was recorded in 61.5% of cases.
CONCLUSIONS: Surgical resection is the treatment of choice for jugular foramen meningiomas. Among the various surgical techniques proposed for dealing with these lesions, we prefer the POTS approach alone or combined with the translabyrinthine or transotic approaches. Despite the advances in skull base surgery, new postoperative lower cranial nerve deficits still represent a challenge.

PMID 17690614
O Tucha, C Smely, K W Lange
Effects of surgery on cognitive functioning of elderly patients with intracranial meningioma.
Br J Neurosurg. 2001 Apr;15(2):184-8.
Abstract/Text Few data are available concerning the outcome of surgical removal of intracranial meningioma in elderly patients. Surgical criteria and prognostic factors are considerations in the decision as to whether neurosurgical removal should be attempted in elderly patients. The present study appears to be the first to examine the cognitive functioning of patients (n = 33) with intracranial meningiomas in the seventh and eighth decades of life prior to and following surgery. The time period between pre- and postoperative assessment was between 12 and 23 weeks. Twenty healthy subjects were also examined. For neuropsychological assessment, standardized test procedures including the examination of memory, attention, visuo-constructive abilities and executive functions were used. No significant deterioration of cognitive functioning was found following surgery. Elderly patients should not therefore be denied meningioma surgery purely on the basis of the risk of postoperative deterioration of mental functioning.

PMID 11360390
G Wilms, M Lammens, G Marchal, F Van Calenbergh, C Plets, L Van Fraeyenhoven, A L Baert
Thickening of dura surrounding meningiomas: MR features.
J Comput Assist Tomogr. 1989 Sep-Oct;13(5):763-8.
Abstract/Text Thickening of the dura in continuity with a convexity meningioma was noted on T1-weighted magnetic resonance (MR) images in seven patients. In five cases the corresponding CT image of the lesions was typical of meningioma. In two other cases the CT image of the lesions was atypical, owing to cyst formation in one and extensive edema in the other. After intravenous injection of paramagnetic contrast medium in four patients, the thickened dura demonstrated contrast enhancement at a variable distance from the tumor. In three patients the thickened dura was confirmed surgically. Pathology, available in one case, showed the thickened dura to correspond to tumoral extension within or around the dura. Magnetic resonance demonstration of thickening of the dura in continuity with a mass at the cerebral convexity may prove to be of importance in the differentiation of atypical lesions on CT and MR, especially with lower field magnets. Moreover, it could provide useful information to the neurosurgeon for more complete resection of the tumor.

PMID 2778133
F Maiuri, G Iaconetta, O de Divitiis, S Cirillo, F Di Salle, M L De Caro
Intracranial meningiomas: correlations between MR imaging and histology.
Eur J Radiol. 1999 Jul;31(1):69-75.
Abstract/Text The authors have examined the relationship between magnetic resonance imaging (MRI) and histopathological features in 35 surgically verified intracranial meningiomas. Tumor signals on T1-weighted images were rather similar regardless of the histologic subtype of the tumors. On T2-weighted images, hypointense meningiomas were mainly fibroblastic and hyperintense tumors were mainly syncytial and angioblastic, and partly transitional. Isointense tumors were mainly transitional and partly fibroblastic and syncytial. The authors conclude that the signal intensity of the MRI may be useful in the preoperative characterization of intracranial meningiomas. T1-weighted images may predict the presence of cysts and intratumoral blood vessels; whereas T2-weighted images can give information about histological subtype, vascularity and consistency. Meningiomas hyperintense to the cortex on T2 are usually soft, more vascular and more frequently of syncytial or angioblastic subtype; tumors hypointense or hypo-isointense on T2 tend to have a more hard consistency and are more often of fibroblastic or transitional subtype.

PMID 10477102
G Odake
Cystic meningioma: report of three patients.
Neurosurgery. 1992 Jun;30(6):935-40.
Abstract/Text Three patients with cystic meningioma are reported. The computed tomographic scans or magnetic resonance images of these tumors resembled those of a glial or metastatic tumor with cystic or necrotic changes. There is no definitive method for preoperatively differentiating cystic meningiomas from the more common malignant glioma. Angiographic evaluation and collaboration with a neuropathologist are important for the recognition of these potentially curable neoplasms.

PMID 1614600
José Carlos Lynch, Leandro Alcy Sales Ferreira, Leonardo Welling, Renata Cardoso Schulz
Multiple intracranial meningiomas: diagnosis, biological behavior and treatment.
Arq Neuropsiquiatr. 2008 Sep;66(3B):702-7.
Abstract/Text UNLABELLED: Multiple intracranial meningiomas (MIM) are a rare pathology when not associated with neurofibromatosis. The prevalence rate of those tumors varied from 2.3 to 8.9% of all intracranial meningiomas.
OBJECTIVE: To present, analyze and discuss the cases of seven patients diagnosed with multiple intracranial meningiomas, describing their clinical and histological characteristics, as well as their biological behavior.
METHOD: The patients records, surgical descriptions, imaging studies and the histopathological exams were retrospectively reviewed. This is the largest series of MIM publisted in Brazil.
RESULTS: This sample consists of five women and two men. The age varied from 42 to 84 (average 53.8). Twenty-two meningiomas were identified and varied from 1.5 to 192 cm(3), with an 62.8 cm(3) average volume. The number of procedures varied from 1 to 5 per patient. No surgical death occurred in this series.
CONCLUSION: Despite the multiplicity of tumors, number of recurrences, the new tumors, repeated operations and re-operations, radiotherapy and a number of postoperative complications, the patients experienced a long survival in conjunction with a fairly good quality of life.

PMID 18949266
S Okuno, H Touho, H Ohnishi, J Karasawa
Falx meningioma presenting as acute subdural hematoma: case report.
Surg Neurol. 1999 Aug;52(2):180-4.
Abstract/Text BACKGROUND: Acute subdural hematomas caused by meningiomas have been rarely encountered. Pathophysiologic mechanisms and clinical considerations in these patients have not been sufficiently explored. We addressed the possible mechanism of spontaneous hemorrhage in our case and briefly discuss the optimal treatment.
CASE DESCRIPTION: This case of falx meningioma presenting as an acute subdural hematoma in a 78-year-old woman is described. On initial computed tomography (CT), an enhancing tumor of the falx appeared to be the cause of hemorrhage. Only faint contrast staining in the periphery of the tumor was seen on right external carotid arteriograms, with no evidence of other vascular supply. Extravasation of contrast material during the procedure occurred suddenly and was successfully treated by endovascular embolization using a microcatheter. The hematoma was emergently evacuated with gross total removal of the tumor. Pathologic examination confirmed a transitional meningioma with abundant hyalinized structures. Disruption of a thin-walled vessel adjacent to the tumor capsule was assumed to be the site of hemorrhage.
CONCLUSIONS: The longstanding ischemia of the tumor was considered to have produced the deposition of hyalin in the tissue, which changed the hemodynamics within the tumor, producing vascular stress leading to rupture. The prognosis of patients with meningiomas complicated by acute subdural hematoma is generally poor, with mortality reported in approximately one-half of such patients. Surgical exploration is the most effective treatment and should be conducted before irreversible brain damage has occurred.

PMID 10447287
WHO classification of Tumours of the Central Nervous System, 2016.Revised 4th edition.
S J Schnitt, H Vogel
Meningiomas. Diagnostic value of immunoperoxidase staining for epithelial membrane antigen.
Am J Surg Pathol. 1986 Sep;10(9):640-9.
Abstract/Text Meningiomas are composed of cells which display both mesenchymal and epithelial features. To investigate the epithelial nature of these cells, we studied the distribution of epithelial membrane antigen (EMA) in 22 meningiomas; for comparison, we also studied eight central schwannomas, neoplasms with which meningiomas sometimes may be confused histologically. All 22 meningiomas (12 transitional, six meningotheliomatous, three fibroblastic, and one psammomatous) demonstrated immunoreactive EMA, whereas all eight schwannomas were EMA-negative. There was no consistent relationship between histologic growth pattern and nature of EMA staining in the meningiomas: meningothelial areas, spindle cell areas, and whorls all showed EMA immunoreactivity of varying degrees. We also evaluated the distribution of S-100 protein and keratin in these tumors. All schwannomas showed diffuse S-100 positivity, which was often more intense in the nuclei than in the cytoplasm. In nine meningiomas (41%), S-100 immunostaining was observed, but this was usually focal, and nuclear staining was never more intense than cytoplasmic staining. One meningioma, but none of the schwannomas, showed clusters of keratin-positive cells. We conclude the following: EMA immunoreactivity is a characteristic feature of meningiomas, regardless of pattern of growth, and the combination of immunoperoxidase staining for EMA and S-100 protein may be used to distinguish meningiomas from schwannomas in problematic cases.

PMID 2428264
A Perry, B W Scheithauer, S L Stafford, P C Abell-Aleff, F B Meyer
"Rhabdoid" meningioma: an aggressive variant.
Am J Surg Pathol. 1998 Dec;22(12):1482-90.
Abstract/Text It is has been suggested that rhabdoid morphology is associated with a poor prognosis, regardless of tumor histogenesis. We report a series of 15 meningiomas with rhabdoid features. Nine patients had undergone multiple resections. In six, the rhabdoid component was histologically apparent only in recurrences. Rhabdoid morphology was defined as sheets of loosely cohesive cells with eccentric nuclei and hyaline, paranuclear inclusions. Ultrastructurally, the latter consisted of whorls of intermediate filaments often entrapping lysosomes or other organelles. Meningothelial features included whorl formation and nuclear pseudoinclusions, immunohistochemical coexpression of vimentin and epithelial membrane antigen, and the ultrastructural finding of interdigitating cell membranes and intercellular junctions. At the histologic level, a conventional meningioma component was noted in most tumors; only four lesions were entirely rhabdoid. Histologic malignancy (brain invasion or anaplasia) was observed in nine cases, another two tumors being considered malignant on the basis of extracranial metastasis. In the majority, increased cell proliferation was evidenced by a high mitotic rate or MIB-1 LI. At last follow-up, 13 patients (87%) had experienced at least one recurrence and 8 (53%) were dead of disease. Median time to death was 5.8 years after initial surgery and 3.1 years after the first appearance of rhabdoid morphology. Our findings corroborate those from a smaller series recently reported by Kepes et al. on the same entity (Kepes JJ, Moral LA, Wilkinson SB, Abdullah A, Llena JF. Rhabdoid transformation of tumor cells in meningiomas: A histologic indication of increased proliferative activity. Report of four cases. Am J Surg Pathol 1998;22:231-8). They further suggest that rhabdoid meningiomas are highly aggressive tumors and that the rhabdoid phenotype represents a marker of malignant transformation in meningiomas.

PMID 9850174
V J Amatya, Y Takeshima, K Sugiyama, K Kurisu, T Nishisaka, T Fukuhara, K Inai
Immunohistochemical study of Ki-67 (MIB-1), p53 protein, p21WAF1, and p27KIP1 expression in benign, atypical, and anaplastic meningiomas.
Hum Pathol. 2001 Sep;32(9):970-5. doi: 10.1053/hupa.2001.27119.
Abstract/Text Histologic grading of meningiomas has prognostic and clinical therapeutic implications. Meningiomas were histologically classified into 3 different World Health Organization grades. Grade II, an atypical meningioma, was defined by major and various minor histologic criteria. However, these histologic criteria sometimes are not fulfilled, and other criteria are necessary. We studied and analyzed the immunohistochemical expression of MIB-1, p53, p21WAF1, p27KIP1 proteins in 146 cases of meningiomas, including 109 benign, 27 atypical, and 10 anaplastic meningiomas. Most of the benign meningiomas expressed low MIB-1 labeling index (mean, 1.5%), and fewer cases had p53 protein expression. In contrast, the anaplastic meningiomas had a high labeling index of MIB-1 (mean, 19.5%) and always expressed p53 protein, with a mean labeling index of 6.3%. The atypical meningiomas had MIB-1 and p53 labeling indexes in the range between benign and anaplastic meningiomas, with mean labeling indexes of 8.1% and 3.5%, respectively. These expressions were statistically significant among benign, atypical, and anaplastic meningiomas (P <.001). We conclude that the immunohistochemistry of MIB-1 and p53 protein will be valuable in discriminating atypical meningiomas from benign or anaplastic meningiomas, at least in histologically borderline cases. In addition, we also found direct correlation of p21 and inverse correlation of p27 expressions in meningiomas with increasing histologic grade and proliferative index.

Copyright 2001 by W.B. Saunders Company
PMID 11567227
Donald Ming-Tak Ho, Chih-Yi Hsu, Ling-Tan Ting, Hung Chiang
Histopathology and MIB-1 labeling index predicted recurrence of meningiomas: a proposal of diagnostic criteria for patients with atypical meningioma.
Cancer. 2002 Mar 1;94(5):1538-47.
Abstract/Text BACKGROUND: Although various histopathologic features have been associated with aggressive behavior or recurrence of meningiomas, there is little agreement about which features are the most important and in what combination. The objective of this study was to formulate diagnostic criteria for atypical meningioma.
METHODS: Eighty-three patients with meningiomas who underwent macroscopic total resection and had been followed until they developed recurrent disease or for at least 10 years were studied. Thirteen histopathologic parameters that related to recurrence of the tumor were evaluated in each patient. All possible combinations of histologic parameters that were related significantly to recurrence were used to formulate scoring models. The model that included the fewest parameters and that could distinguish tumor recurrence best within 10 years was chosen as the final model.
RESULTS: The final model included three parameters: loss of architecture, mitoses > or= 1.5/mm2, and necrosis. Of the 52 tumors with a score < 2 (0 or 1 of the 3 parameters), all except 1 tumor did not recur within 10 years, and they were all considered benign meningiomas. Of the 31 tumors with a score > or = 2 (2 or 3 of the 3 parameters), 94% recurred within 10 years (76% recurred within 5 years), and they were considered atypical meningiomas. The estimated 5-year and 10-year recurrence rates for the benign meningiomas were 0.0% and 1.9%, respectively, for benign meningiomas and 71.0% and 93.5%, respectively, for atypical meningiomas (P < 0.001). The estimated 5-year and 10-year mortality rates also were significantly different (0.0% and 0.0% vs. 22.1% and 26.7%, respectively; P < 0.001). The MIB-1 labeling index (LI) for the entire group studied ranged from 0.4 to 33.5 (mean LI, 8.4). Fifty-two tumors with an LI of < 10 did not recur within 10 years. Of the 31 tumors with an LI > or = 10, 97% recurred (71% within 5 years).
CONCLUSIONS: Histopathology and MIB-1 LI were able to predict clinical outcomes of patients with meningioma. The authors propose that atypical meningioma may be diagnosed when two of the following three criteria are present: loss of architecture, mitoses > or = 1.5/mm2, and necrosis.

Copyright 2002 American Cancer Society.
PMID 11920512
F Roser, M Samii, H Ostertag, M Bellinzona
The Ki-67 proliferation antigen in meningiomas. Experience in 600 cases.
Acta Neurochir (Wien). 2004 Jan;146(1):37-44; discussion 44. doi: 10.1007/s00701-003-0173-4. Epub 2003 Dec 22.
Abstract/Text BACKGROUND: Meningiomas are mostly benign tumours that can be cured by surgical resection. Because meningiomas tend to recur, long term management in patients with subtotal tumour resection remains controversial. Previous studies have shown that the proliferation potential of meningiomas by Ki-67 labelling indices (LI) might predict their natural history. The purpose of this study was to analyse the reliability of Ki-67-labelling index in predicting the behaviour of meningiomas, and to help the neurosurgeon in establishing better follow up criteria and long term management strategies for these patients.
METHOD: From 1990 to 2000 1328 meningiomas have been operated in our Neurosurgical Department. A total of 600 tumours were examined immunohistochemically using the Mib-1 monoclonal antibody. Clinical charts of the patients including surgical, histological and follow up records, as well as imaging studies were analysed retrospectively. Ki-67 LI were correlated with neuroradiological findings, 3D volumetric studies, histological subtype, recurrence-free survival, grade of resection, consistency of tumour tissue, location, osseous involvement, en plaque appearance, vascularity and progesterone-receptor status.
FINDINGS: Among the 600 patients analysed, there were 66% females (mean LI 3.8%) and 34% males (mean LI 5.7%), including 20 neurofibromatosis-type-2 (NF-II) patients with a mean LI of 5.2%. Histological grading revealed 91% WHO degrees I meningiomas (mean LI 3.28%), 7% WHO degrees II (mean LI 9.95%) and 2% WHO degrees III (mean LI 12.18%). Labelling indices in recurrent meningiomas increased from initial resection to a fourth local resection. A significant correlation between negative progesteron-receptor status and high tumour vascularity with high Ki-67 LI was seen. Ki67 was not a statistically significant predictor of survival time in totally excised WHO degrees I meningiomas.
INTERPRETATION: Mib-1 is one important tool in addition to routine histological evaluation, but a combination of clinical factors and particularly the extent of surgical resection, along with the biological features of the tumour, should influence the decision of the neurosurgeon to the patient follow up.

PMID 14740263
E Karamitopoulou, E Perentes, M Tolnay, A Probst
Prognostic significance of MIB-1, p53, and bcl-2 immunoreactivity in meningiomas.
Hum Pathol. 1998 Feb;29(2):140-5.
Abstract/Text Sixty biopsy specimens of meningiomas, including 37 benign, 10 atypical, and 13 malignant meningiomas, were examined immunohistochemically using the monoclonal antibodies MIB-1 (a cell proliferation marker), p53, and bcl-2 (two apoptosis-associated markers). Benign meningiomas were subdivided into two groups: group 1, 29 tumors without recurrence; and group 2, eight tumors with recurrence after complete surgical resection. The mean MIB-1 labeling index (LI) values+/-SD were 1.3+/-3.2% for the benign, 9.3+/-6.9% for the atypical, and 15.0+/-16.9% for the anaplastic meningiomas. The mean MIB-1 LI+/-SD in group 1 tumors (n = 29) was 1.06+/-1.15%, and in group 2 tumors (n = 8), 2.3+/-4.76% (P = .028). p53 protein expression was found in 10.8% of the benign (10.34% of group 1 and 12.5% of group 2), 50% of the atypical, and 77% of the anaplastic meningiomas. bcl-2 protein expression was observed in 21.6% of the benign, 20% of the atypical, and 46.1% of the anaplastic meningiomas. Among the benign meningiomas, group 2 tumors expressed significantly more often bcl-2 protein (62.5%) than group 1 neoplasms (10.3%). Our results indicate that (1) in meningiomas, a good correlation exists between histological grading, MIB-1 and p53 protein expression, and (2) in benign meningiomas, the presence of bcl-2 protein expression together with high MIB-1 LI are associated with unfavorable prognosis of the disease.

PMID 9490273
S K Ludwin, L J Rubinstein, D S Russell
Papillary meningioma: a malignant variant of meningioma.
Cancer. 1975 Oct;36(4):1363-73.
Abstract/Text A series of 17 meningiomas histologically characterized by a papillary pattern is reported. This pattern was invariably associated with other histologic features of malignancy. The tumors often displayed aggressive clinical behavior marked by a high rate of local recurrence or the development of distant metastases. A relatively large proportion occurred in children. It is suggested that this variant of meningioma is sufficiently characteristic to justify its separation as a distinct clinicopathologic entity.

PMID 1175134
Douglas Kondziolka, David Mathieu, L Dade Lunsford, Juan J Martin, Ricky Madhok, Ajay Niranjan, John C Flickinger
Radiosurgery as definitive management of intracranial meningiomas.
Neurosurgery. 2008 Jan;62(1):53-8; discussion 58-60. doi: 10.1227/01.NEU.0000311061.72626.0D.
Abstract/Text OBJECTIVE: Stereotactic radiosurgery has become an important primary or adjuvant minimally invasive management strategy for patients with intracranial meningiomas with the goals of long-term tumor growth prevention and maintenance of patient neurological function. We evaluated clinical and imaging outcomes of meningiomas stratified by histological tumor grade.
METHODS: The patient cohort consisted of 972 patients with 1045 intracranial meningiomas managed during an 18-year period. The series included 70% women, 49% of whom had undergone a previous resection and 5% of whom had received previous fractionated radiation therapy. Tumor locations included middle fossa (n = 351), posterior fossa (n = 307), convexity (n = 126), anterior fossa (n = 88), parasagittal region (n = 113), or other (n = 115).
RESULTS: The overall control rate for patients with benign meningiomas (World Health Organization Grade I) was 93%. In those without previous histological confirmation (n = 482), tumor control was 97%. However, for patients with World Health Organization Grade II and III tumors, tumor control was 50 and 17%, respectively. Delayed resection after radiosurgery was necessary in 51 patients (5%) at a mean of 35 months. After 10 years, Grade 1 tumors were controlled in 91% (n = 53); in those without histology, 95% (n = 22) were controlled. None of the patients developed a radiation-induced tumor. The overall morbidity rate was 7.7%. Symptomatic peritumoral imaging changes developed in 4% of the patients at a mean of 8 months.
CONCLUSION: Stereotactic radiosurgery provided high rates of tumor growth control or regression in patients with benign meningiomas with low risk. This study confirms the role of radiosurgery as an effective management choice for patients with small to medium-sized symptomatic, newly diagnosed or recurrent meningiomas of the brain.

PMID 18300891
Federico Colombo, Leopoldo Casentini, Carlo Cavedon, Paolo Scalchi, Stefania Cora, Paolo Francescon
Cyberknife radiosurgery for benign meningiomas: short-term results in 199 patients.
Neurosurgery. 2009 Feb;64(2 Suppl):A7-13. doi: 10.1227/01.NEU.0000338947.84636.A6.
Abstract/Text OBJECTIVE: To present initial, short-term results obtained with an image-guided radiosurgery apparatus (CyberKnife; Accuray, Inc., Sunnyvale, CA) in a series of 199 benign intracranial meningiomas.
METHODS: Selection criteria included lesions unsuitable for surgery and/or remnants after partial surgical removal. All patients were either symptomatic and/or harboring growing tumors. Ninety-nine tumors involved the cavernous sinus; 28 were in the posterior fossa, petrous bone, or clivus; and 29 were in contact with anterior optic pathways. Twenty-two tumors involved the convexity, and 21 involved the falx or tentorium. One hundred fourteen patients had undergone some kind of surgical removal before radiosurgery. Tumor volumes varied from 0.1 to 64 mL (mean, 7.5 mL) and radiation doses ranged from 12 to 25 Gy (mean, 18.5 Gy). Treatment isodoses varied from 70 to 90%. In 150 patients with lesions larger than 8 mL and/or with tumors situated close to critical structures, the dose was delivered in 2 to 5 daily fractions.
RESULTS: The follow-up periods ranged from 1 to 59 months (mean, 30 months; median, 30 months). The tumor volume decreased in 36 patients, was unchanged in 148 patients, and increased in 7 patients. Three patients underwent repeated radiosurgery, and 4 underwent operations. One hundred fifty-four patients were clinically stable. In 30 patients, a significant improvement of clinical symptoms was obtained. In 7 patients, neurological deterioration was observed (new cranial deficits in 2, worsened diplopia in 2, visual field reduction in 2, and worsened headache in 2).
CONCLUSION: The introduction of the CyberKnife extended the indication to 63 patients (>30%) who could not have been treated by single-session radiosurgical techniques. The procedure proved to be safe. Clinical improvement seems to be more frequently observed with the CyberKnife than in our previous linear accelerator experience.

PMID 19165077
Michael E Sughrue, Nader Sanai, Gopal Shangari, Andrew T Parsa, Mitchel S Berger, Michael W McDermott
Outcome and survival following primary and repeat surgery for World Health Organization Grade III meningiomas.
J Neurosurg. 2010 Aug;113(2):202-9. doi: 10.3171/2010.1.JNS091114.
Abstract/Text OBJECT: Despite an increased understanding of the biology of malignant meningioma tumor progression, there is a paucity of published clinical data on factors affecting outcomes following treatment for these lesions. The authors present the largest case series to date dealing with these tumors, providing analysis of 63 patients.
METHODS: The authors identified all patients undergoing resection of WHO Grade III tumors at their institution over a 16-year period. They analyzed clinical data from these patients, and performed Kaplan-Meier and Cox regression analyses to determine the impact of different clinical characteristics and different treatment modalities on survival following initial and repeat surgery for these lesions.
RESULTS: Sixty-three patients met inclusion criteria and were analyzed further. The median clinical follow-up time was 5 years (range 1-22 years). The 2-, 5-, and 10-year overall survival rates following initial operation were 82, 61, and 40%, respectively. Kaplan-Meier analysis demonstrated a marked survival benefit with repeat operation (53 vs 25 months, p = 0.02). Interestingly, patients treated with near-total resection experienced improved overall survival when compared with patients treated with gross-total resection at initial (p = 0.035) and repeat operations (p = 0.005). Twelve (19%) of 63 patients experienced significant neurological morbidity referable to the resection of their tumors.
CONCLUSIONS: Surgery is an effective treatment for WHO Grade III meningiomas at presentation and recurrence; however, aggressive attempts to achieve gross-total resection can be associated with significant neurological risk.

PMID 20225922
P Black, S Kathiresan, W Chung
Meningioma surgery in the elderly: a case-control study assessing morbidity and mortality.
Acta Neurochir (Wien). 1998;140(10):1013-6; discussion 1016-7.
Abstract/Text GOAL: To assess the morbidity and mortality of meningioma surgery in patients over age 65 and compare our results with matched controls and with the present literature on meningioma surgery in the elderly.
METHODS: An evaluation of 114 patients undergoing meningioma resection divided into two groups: 57 patients aged 65-87, and a control group of 57 patients aged 25-64 matched by ASA status and tumor site. Operative complications, 30-day mortality, and pre- and postoperative neurologic status were assessed with follow up one to three months.
RESULTS: Complication rates in the two groups were similar and were low. Four out of fifty-seven elderly patients (7.0%) had a surgical complication compared with five younger patients (8.8%) Excluding asymptomatic DVT detected by screening, three elderly patients had medical complications (5.2%) compared with two controls (3.5%). The vast majority of patients-93% of the elderly group and 89.4% in the controls--experienced either improvement or no change in neurologic status at followup one to three months after surgery. There was one death among elderly patients within thirty days for a mortality rate of 1.8% compared with no mortality in the case control group. The elderly patient who died was an 80-year old man who died of pneumonia in a rehabilitation hospital three weeks after surgery. Our study group of 57 patients was compared by tumor site and preoperative general health status to other series in the literature. In a review from the literature of 417 patients over age 65 who underwent meningioma surgery, the average 30-day mortality was 16%. The complication rate averaged 39%.
DISCUSSION: Our lower morbidity and mortality rates after meningioma surgery in the elderly may be a result of patient selection, surgical technique, or excellent pre- and post-operative care by the resident staff, anesthesiologists, and nurses. It suggests, however, that elderly patients can have meningioma surgery safely.

PMID 9856244
R Buhl, A Hasan, A Behnke, H M Mehdorn
Results in the operative treatment of elderly patients with intracranial meningioma.
Neurosurg Rev. 2000 Mar;23(1):25-9.
Abstract/Text With life expectancy in the industrial nations increasing during recent years, the number of patients older than 70 years with intracranial tumours and, especially, meningiomas is rising. To evaluate the indications for operative treatment, we reviewed 66 patients older than 70 years who were operated upon for intracranial meningioma in our department between 1991 and 1997. The mean age was 75 years. The oldest patients were 86 years old. Thirteen patients with recurrent meningiomas were operated upon. The mortality rate was 7.6%. Neurological symptoms improved in 38 patients (57.6%), were unchanged in 11 (16.6%), and deteriorated in 12 (18.2%). Patients with recurrent meningiomas seem to have a higher operative risk and their outcome is worse than after a primary operation. In general, there were good postoperative results in patients with few concomitant diseases, small meningiomas, small edema, short time of operation, and accessible location (convexity rather than skull base). Age in general is not a contraindication for operation. In cases of incidental findings of small meningiomas, we recommend observation and MRI follow-up. Symptomatic meningiomas should be removed whenever there is an acceptable risk from an internal or anaesthesiological point of view.

PMID 10809483
日本脳神経外科学会、日本病理学会編:脳腫瘍取扱い規約第4版.金原出版、2018..
日本脳ドック学会/脳卒中・認知症予防のための医学会 脳ドックのガイドライン2019改訂委員会編:脳ドックのガイドライン2019.改訂第5版. 響文社. 2019.
Tetsuo Hashiba, Naoya Hashimoto, Shuichi Izumoto, Tsuyoshi Suzuki, Naoki Kagawa, Motohiko Maruno, Amami Kato, Toshiki Yoshimine
Serial volumetric assessment of the natural history and growth pattern of incidentally discovered meningiomas.
J Neurosurg. 2009 Apr;110(4):675-84. doi: 10.3171/2008.8.JNS08481.
Abstract/Text OBJECT: Due to advances in neuroimaging and the increasing use of imaging to screen for brain disease ("brain checkups"), meningiomas are now often detected as an incidental finding. The natural history of these asymptomatic meningiomas remains unclear, however. In this study, the authors investigated the natural history and growth pattern of incidentally detected meningiomas using serial volumetric assessment and regression analysis.
METHODS: In 70 patients with incidentally discovered meningiomas who underwent follow-up for longer than 1 year, tumor volumes were calculated volumetrically at each follow-up visit, and tumor growth was determined. In patients with tumor growth, regression analysis was performed to determine the pattern of growth.
RESULTS: Forty-four tumors exhibited growth and 26 did not. In a regression analysis, 16 of the tumors that grew followed an exponential growth pattern and 15 exhibited linear growth patterns. The presence of calcification was the only imaging characteristic that significantly distinguished the group with tumor growth from that without, although no radiological characteristics significantly distinguished the exponential growth group from the linear growth group. Two patients with obvious tumor growth underwent surgical removal and the pathological specimens extracted showed a high proliferative potential.
CONCLUSIONS: The authors found that incidentally discovered meningiomas did not always follow an exponential growth pattern but often exhibited more complex patterns of growth. Serial monitoring of tumor volumes and regression analysis may reveal the growth pattern of incidental meningiomas and provide information useful for determining treatment strategy.

PMID 19061353
Soichi Oya, Seon-Hwan Kim, Burak Sade, Joung H Lee
The natural history of intracranial meningiomas.
J Neurosurg. 2011 May;114(5):1250-6. doi: 10.3171/2010.12.JNS101623. Epub 2011 Jan 21.
Abstract/Text OBJECT: Despite the increased detection of incidental or small meningiomas, the lesion's natural history is largely unknown.
METHODS: One year or longer of follow-up was conducted in 244 patients with 273 meningiomas managed conservatively by a single surgeon between 2003 and 2008. Data were stratified according to age, sex, tumor location, symptoms, initial tumor diameter, calcification, MR imaging intensity, and edema. Linear tumor growth was defined as a 2-mm or larger increase in the maximum diameter in any direction of the tumor. Volumetric analysis (ImageJ version 1.43) was also conducted in 154 of 273 meningiomas for which complete radiological data were available in the form of DICOM files throughout the follow-up period. A volume increase greater than 8.2% was regarded as significant because the preliminary volumetry based on 20 randomly selected meningiomas showed that the average SD was 4.1%.
RESULTS: Linear growth was observed in 120 tumors (44.0%) with a mean follow-up of 3.8 years. Factors related to tumor growth were age of 60 or younger (p = 0.0004), absence of calcification (p = 0.027), MR imaging T2 signal hyperintensity (p = 0.021), and edema (p = 0.018). Kaplan-Meier analysis and Cox proportional hazards regression analysis revealed that age 60 or younger (hazard ratio [HR] 1.54, 95% CI 1.05-2.30, p = 0.026), initial tumor diameter greater than 25 mm (HR 2.23, 95% CI 1.44-3.38, p = 0.0004), and the absence of calcification (HR 4.57, 95% CI 2.69-8.20, p < 0.0001) were factors associated with a short time to progression. Volumetric growth was seen in 74.0% of the cases. Factors associated with a higher annual growth rate were male sex (p = 0.0002), initial tumor diameter greater than 25 mm (p < 0.0001), MR imaging T2 signal hyperintensity (p = 0.0001), presence of symptoms (p = 0.037), and edema (p < 0.0001).
CONCLUSIONS: Although the authors could obtain variable results depending on the measurement method, the data demonstrate patients younger than 60 years of age and those with meningiomas characterized by hyperintensity on T2-weighted MR imaging, no calcification, diameter greater than 25 mm, and edema need to be observed more closely. Volumetry was more sensitive to detecting tumor growth than measuring the linear diameter.

PMID 21250802
Michael E Sughrue, Martin J Rutkowski, Derick Aranda, Igor J Barani, Michael W McDermott, Andrew T Parsa
Treatment decision making based on the published natural history and growth rate of small meningiomas.
J Neurosurg. 2010 Nov;113(5):1036-42. doi: 10.3171/2010.3.JNS091966. Epub 2010 Apr 30.
Abstract/Text OBJECT: Definitive data allowing clinicians to predict which meningioma patients will fail to respond to conservative management are lacking. To address this need, the authors systematically reviewed the published literature regarding the natural history of small, untreated meningiomas.
METHODS: The authors performed a systematic review of the existing literature on untreated meningiomas that were followed with serial MR imaging. They summarize the published linear rates of tumor growth, and the risk factors for development of new or worsened symptoms during follow-up by using a stratified chi-square test.
RESULTS: The search methods identified 22 published studies reporting on 675 patients with untreated meningiomas followed by serial MR imaging. Linear growth rates varied significantly: no growth was the most common rate, although reports of more aggressive tumors noted growth rates of up to a 93% linear increase in size per year. The authors found that few patients with initial tumor diameters < 2 cm went on to develop new or worsened symptoms over a median follow-up period of 4.6 years. Patients with initial tumor diameters of 2-2.5 cm demonstrated a marked difference in the rate of symptom progression if their tumors grew > 10% per year, compared with those tumors growing ≤ 10% per year (42% vs 0%; p < 0.001, chi-square test). Patients with tumors between > 2.5 and 3 cm in initial size went on to develop new or worsened symptoms 17% of the time.
CONCLUSIONS: This systematic review of the literature regarding the clinical behavior of untreated meningiomas suggests that most meningiomas ≤ 2.5 cm in diameter do not proceed to cause symptoms in the approximately 5-year period following their discovery. Those that do cause symptoms can usually be predicted with close radiographic follow-up. Based on these findings, the authors suggest the importance of observation in the early course of treatment for small asymptomatic meningiomas, especially those with an initial diameter < 2 cm.

PMID 20433281
Naoya Hashimoto, Carter S Rabo, Yoshiko Okita, Manabu Kinoshita, Naoki Kagawa, Yasunori Fujimoto, Eiichi Morii, Haruhiko Kishima, Motohiko Maruno, Amami Kato, Toshiki Yoshimine
Slower growth of skull base meningiomas compared with non-skull base meningiomas based on volumetric and biological studies.
J Neurosurg. 2012 Mar;116(3):574-80. doi: 10.3171/2011.11.JNS11999. Epub 2011 Dec 16.
Abstract/Text OBJECT: The precise natural history of incidentally discovered meningiomas (IDMs) remains unknown. It has been reported that for symptomatic meningiomas, tumor location can be used to predict growth. As to whether the same is true for IDMs has not been reported. This study aims to answer this question and provide biological evidence for this assumption by extending the study to involve symptomatic cases.
METHODS: A total of 113 IDMs were analyzed by fine volumetry. A comparison of growth rates and patterns between skull base and non-skull base IDMs was made. Subsequently, materials obtained from 210 patients with symptomatic meningiomas who were treated in the authors' hospital during the same period were included for a biological comparison between skull base and non-skull base tumors using the MIB-1 index.
RESULTS: The 110 patients with IDMs included 93 females and 17 males, with a mean follow-up period of 46.9 months. There were 38 skull base (34%) and 75 non-skull base (66%) meningiomas. Forty-two (37%) did not exhibit growth of more than 15% of the volume, whereas 71 (63%) showed growth. Only 15 (39.5%) of 38 skull base meningiomas showed growth, whereas 56 (74.7%) of 75 non-skull base meningiomas showed growth (p = 0.0004). In the 71 IDMs (15 skull base and 56 non-skull base), there was no statistical difference between the 2 groups in terms of mean age, sex, follow-up period, or initial tumor volume. However, the percentage of growth (p = 0.002) was significantly lower and the doubling time (p = 0.008) was significantly higher in the skull base than in the non-skull base tumor group. In subsequently analyzed materials from 94 skull base and 116 non-skull base symptomatic meningiomas, the mean MIB-1 index for skull base tumors was markedly low (2.09%), compared with that for non-skull base tumors (2.74%; p = 0.013).
CONCLUSIONS: Skull base IDMs tend not to grow, which is different from non-skull base tumors. Even when IDMs grow, the rate of growth is significantly lower than that of non-skull base tumors. The same conclusion with regard to biological behavior was confirmed in symptomatic cases based on MIB-1 index analyses. The authors' findings may impact the understanding of the natural history of IDMs, as well as strategies for management and treatment of IDMs and symptomatic meningiomas.

PMID 22175721
Satoshi Nakasu, Yoko Nakasu
Natural History of Meningiomas: Review with Meta-analyses.
Neurol Med Chir (Tokyo). 2020 Mar 15;60(3):109-120. doi: 10.2176/nmc.ra.2019-0213. Epub 2020 Jan 31.
Abstract/Text Observation has been a mainstay in asymptomatic meningiomas, but it may increase the risk associated with treatment due to tumor enlargement and the aging of patients. Understanding the natural course of meningiomas is important to provide appropriate treatment. The majority of previous studies investigated factors related to their growth, but failed to demonstrate their relationship with symptomatic progression (sympP) because of its rarity. We reviewed and meta-analyzed 27 studies that investigated natural courses in asymptomatic or untreated meningiomas to find clinico-radiological factors predictive of radiological progression (radioP), growth speed, and sympP. In results of time-growth analysis, two-thirds of meningiomas showed radioP defined by a volume criterion and the rate approached a plateau at 4-5 years. In growth curve analyses, about half of incidental meningiomas presented decelerating or no growth, while less than one-quarter of them grew exponentially. RadioP, growth speed [annual volume change (AVC) or relative growth rate], and sympP each had different factors related to them. Younger age, non-calcification, and high intensity on T2-weighted image were related to radioP and rapid growth speed, but not to sympP. Tumors in males and those of larger size were likely to be symptomatic in the meta-analysis. AVC (≥2.1 cm3/year) was the strongest indicator of sympP. Apart from perifocal edema, radiological features at up-front imaging may not be useful for predicting sympP. This may be due to dynamic changes of those radiological markers in the long term. Quantified tumor size and growth speed, especially AVC, are important markers for deciding on treatment.

PMID 32009127
Abdurrahman I Islim, Ruwanthi Kolamunnage-Dona, Midhun Mohan, Richard D C Moon, Anna Crofton, Brian J Haylock, Nitika Rathi, Andrew R Brodbelt, Samantha J Mills, Michael D Jenkinson
A prognostic model to personalize monitoring regimes for patients with incidental asymptomatic meningiomas.
Neuro Oncol. 2020 Feb 20;22(2):278-289. doi: 10.1093/neuonc/noz160.
Abstract/Text BACKGROUND: Asymptomatic meningioma is a common incidental finding with no consensus on the optimal management strategy. We aimed to develop a prognostic model to guide personalized monitoring of incidental meningioma patients.
METHODS: A prognostic model of disease progression was developed in a retrospective cohort (2007-2015), defined as: symptom development, meningioma-specific mortality, meningioma growth or loss of window of curability. Secondary endpoints included non-meningioma-specific mortality and intervention.
RESULTS: Included were 441 patients (459 meningiomas). Over a median of 55 months (interquartile range, 37-80), 44 patients had meningioma progression and 57 died (non-meningioma-specific). Forty-four had intervention (at presentation, n = 6; progression, n = 20; nonprogression, n = 18). Model parameters were based on statistical and clinical considerations and included: increasing meningioma volume (hazard ratio [HR] 2.17; 95% CI: 1.53-3.09), meningioma hyperintensity (HR 10.6; 95% CI: 5.39-21.0), peritumoral signal change (HR 1.58; 95% CI: 0.65-3.85), and proximity to critical neurovascular structures (HR 1.38; 95% CI: 0.74-2.56). Patients were stratified based on these imaging parameters into low-, medium- and high-risk groups and 5-year disease progression rates were 3%, 28%, and 75%, respectively. After 5 years of follow-up, the risk of disease progression plateaued in all groups. Patients with an age-adjusted Charlson comorbidity index ≥6 (eg, an 80-year-old with chronic kidney disease) were 15 times more likely to die of other causes than to receive intervention at 5 years following diagnosis, regardless of risk group.
CONCLUSIONS: The model shows that there is little benefit to rigorous monitoring in low-risk and older patients with comorbidities. Risk-stratified follow-up has the potential to reduce patient anxiety and associated health care costs.

© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.
PMID 31603516
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、渡邉裕次、井ノ口岳洋、梅田将光および日本医科大学多摩永山病院 副薬剤部長 林太祐による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
橋本直哉 : 未申告[2024年]
監修:甲村英二 : 特に申告事項無し[2024年]

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