The importance of considering competing risks in recurrence analysis of intracranial meningioma.

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Approaching glioblastoma during COVID-19 pandemic: current recommendations and considerations in Brazil.

BACKGROUND: Cancer patients in general and glioblastoma patients, in particular, have an increased risk of developing complications from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and reaching a balance between the risk of exposure to infection and the clinical benefit of their treatment is ideal. The aggressive behavior of this group of tumors justifies the need for a multidisciplinary team to assist in clinical decisions during the current pandemic. Brazil is now ranked #2 in the number of cases and deaths from COVID-19 pandemic, and existing disparities in the treatment of neuro-oncology patients in Brazil will challenge the clinical and surgical decisions of this population, possibly affecting global survival. OBJECTIVE: To search the literature about the management of glioblastomas during COVID-19 pandemic to guide surgical and clinical decisions in this population of patients in Brazil. METHODS: We performed a systematic search on the PubMed electronic database targeting consensus statements concerning glioblastoma approaches during COVID-19 pandemic up to July 18, 2020. RESULTS: When approaching glioblastoma during the COVID-19 pandemic, important parameters that help in the decision-making process are age, performance status, tumor molecular profile, and patient consent. Younger patients should follow the standard protocol after maximal safe resection, mainly those with MGMT methylated tumors. Aged and underperforming patients should be carefully evaluated, and probably a monotherapy scheme is to be considered. Centers are advised to engage in telemedicine and to elaborate means to reduce local infection. CONCLUSION: Approaching glioblastoma during the COVID-19 pandemic will be challenging worldwide, but particularly in Brazil, where a significant inequality of healthcare exists.

Adult Pilocytic Astrocytomas: A Brazilian Series.

OBJECTIVE: Pilocytic astrocytoma (PA) is rare in adults comprising 5.1% of the primary central nervous system tumors. The aim is to describe the first Brazilian series of adult patients with PA and compare its features with the available literature. METHODS: We retrospectively review all patients 18 years or older with PA from our institution's database from 1991 to 2018. We analyzed information regarding clinical presentation, location, imaging features, extent of resection, adjuvant treatments, and follow-up. RESULTS: Twenty-three patients with PA were analyzed: 60.9% male; median age 26 years. The most frequent symptoms were headache (34.8%) and seizure (26.1%). Temporal and parietal lobes were the most common locations, 21.7% each. All patients underwent a surgical procedure, gross total resection in 40.9%, subtotal resection in 22.7%, and biopsy in 27.3%. Adjuvant treatment with radiotherapy was performed in 2 patients. Only 4 patients had disease progression, 2 after gross total resection and 2 after subtotal resection. They were all alive and without evidence of new progression at the last follow-up (October 2018). Median overall survival was not reached after a median follow-up time of 88.9 months. CONCLUSIONS: This is the first Brazilian series regarding adults with PA, and our patients had a favorable outcome as reported in recent literature reviews. The tumor's prevalence reduces within older patients and supratentorial lesions are more frequent, especially on the temporal lobe. There was no significant relationship between location and progression, although according to the literature the extent of resection remains the most important prognostic factor.

Intravenous Grafts of Human Amniotic Fluid-Derived Stem Cells Reduce Behavioral Deficits in Experimental Ischemic Stroke.

Amniotic fluid has been investigated as new cell source for stem cells in the development of future cell-based transplantation. This study reports isolation of viable human amniotic fluid-derived stem cells, labeled with multimodal iron oxide nanoparticles, and its effect on focal cerebral ischemia-reperfusion injury in Wistar rats. Middle cerebral artery occlusion of 60 min followed by reperfusion for 1 h, 6 h, and 24 h was employed in the present study to produce ischemia and reperfusion-induced cerebral injury in rats. Tests were employed to assess the functional outcome of the sensorimotor center activity in the brain, through a set of modified neurological severity scores used to assess motor and exploratory capacity 24 h, 14, and 28 days after receiving cellular therapy via tail vein. In our animal model of stroke, transplanted cells migrated to the ischemic focus, infarct volume decreased, and motor deficits improved. Therefore, we concluded that these cells appear to have beneficial effects on the ischemic brain, possibly based on their ability to enhance endogenous repair mechanisms.

Intravenous grafts of human amniotic fluid-derived stem cells reduce behavioral deficits in experimental ischemic stroke

Amniotic fluid has been investigated as new cell source for stem cells in the development of future cell-based transplantation. This study reports isolation of viable human amniotic fluid-derived stem cells, labeled with multimodal iron oxide nanoparticles, and its effect on focal cerebral ischemia–reperfusion injury in Wistar rats. Middle cerebral artery occlusion of 60 min followed by reperfusion for 1 h, 6 h, and 24 h was employed in the present study to produce ischemia and reperfusion-induced cerebral injury in rats. Tests were employed to assess the functional outcome of the sensorimotor center activity in the brain, through a set of modified neurological severity scores used to assess motor and exploratory capacity 24 h, 14, and 28 days after receiving cellular therapy via tail vein. In our animal model of stroke, transplanted cells migrated to the ischemic focus, infarct volume decreased, and motor deficits improved. Therefore, we concluded that these cells appear to have beneficial effects on the ischemic brain, possibly based on their ability to enhance endogenous repair mechanisms.

Intravenous grafts of human amniotic fluid-derived stem cells reduce behavioral deficits in experimental ischemic stroke

Amniotic fluid has been investigated as new cell source for stem cells in the development of future cell-based transplantation. This study reports isolation of viable human amniotic fluid-derived stem cells, labeled with multimodal iron oxide nanoparticles, and its effect on focal cerebral ischemia–reperfusion injury in Wistar rats. Middle cerebral artery occlusion of 60 min followed by reperfusion for 1 h, 6 h, and 24 h was employed in the present study to produce ischemia and reperfusion-induced cerebral injury in rats. Tests were employed to assess the functional outcome of the sensorimotor center activity in the brain, through a set of modified neurological severity scores used to assess motor and exploratory capacity 24 h, 14, and 28 days after receiving cellular therapy via tail vein. In our animal model of stroke, transplanted cells migrated to the ischemic focus, infarct volume decreased, and motor deficits improved. Therefore, we concluded that these cells appear to have beneficial effects on the ischemic brain, possibly based on their ability to enhance endogenous repair mechanisms.

Necrosis is a consistent factor to recurrence of meningiomas: should it be a stand-alone grading criterion for grade II meningioma?

The purpose of this study was to evaluate spontaneous necrosis as a possible isolated factor for progression and recurrence in grade I meningiomas classified according to the current World Health Organization (WHO) classification. Meningiomas are the most frequently reported primary intracranial tumours, accounting for more than 35%. The 2016 WHO classification of central nervous system tumors stratifies meningiomas in grades I (benign), II (atypical), and III (malignant), according to histopathological aspects and the risk of progression or recurrence. Among 110 patients with intracranial meningiomas, 70 were WHO grade I meningiomas with no findings of atypia (G1WON), 15 were WHO grade I with necrosis (G1WN), 21 were WHO grade II (G2), and 4 were WHO grade III (G3). The mean follow-up was 5.9 ± 0.2 years. High performance scale (KPS ≥ 80) was different (p < 0.001) between WHO grade I meningiomas without (81.4%) and with (60%) necrosis. The 5-year mortality rate was 1.4, 6.7 and 5.9% for G1WON, G1WN and G2, respectively, with significant difference (p = 0.011) related to the presence of necrosis. The risk of recurrence was 3.7 times higher in G1WN than in G1WON (p = 0.017), and 4.2 times in G2 (p = 0.010). Progression-free survival (PFS) was clearly higher in patients with G1WON compared to G1WN and G2 (p = 0.002 and p < 0.001, respectively). There was no significant difference in PFS between G1WN and G2 (p = 0.692). Retreatment was also superior in meningioma with necrosis. Our findings provide clear statistical data to consider that patients with benign meningiomas and histologic findings of spontaneous necrosis are at increased risk of progression and recurrence compared to those with benign lesion without atypical features. Statistical analysis curves also suggest that these lesions behave more similarly to those currently classified as WHO grade II meningioma.

Unusual Intracerebral Presentation of a Myxoid Neurofibroma.

BACKGROUND: Neurofibromas are benign nerve sheath tumors that usually affect peripheral nerves and are related to neurofibromatosis type 1; however, they have not been described as a cause of intraparenchymal brain tumor. CASE DESCRIPTION: We report a case of intracranial myxoid neurofibroma in a 19-year-old female patient manifested as an intense and progressive cephalea, followed by nausea, vomiting, photophobia, and phonophobia. Computed tomography and magnetic resonance imaging showed an extant, expansive left frontoparietal parafalcine/parasagittal tumor. Histopathologic examination determined S-100 protein and CD34 positivity, as well as sparse expression of Ki67 protein, and indicated Schwann cells with characteristic wavy nuclei and intraneural fibroblasts in a myxoid background. Together, these observations characterized the tumor as myxoid neurofibroma. The tumor was excised, and the patient recovered without deficits and with no signs of recurrence after 6 years of follow-up. CONCLUSIONS: This is a novel presentation of a myxoid neurofibroma. The tumorigenesis mechanisms are likely complex and possibly involve the differentiation of Schwann cells present in adrenergic autonomic nerves in the subarachnoid arterial branches or in trigeminal nerves present in the meningeal convexity.

Low-Grade Oligodendroglioma of the Pineal Region: Case Report.

Background Although germ cell tumors and pineal cell tumors account for most of the histologic tumor subtypes, > 17 different tumors can arise in this location. We report a rare case of a low-grade oligodendroglioma that arose in the pineal region. Clinical Presentation A young woman complaining of a headache underwent magnetic resonance imaging that showed a mass in the pineal region and mild hydrocephalus. A ventriculoperitoneal shunt was performed followed by a near-total tumor removal, due to tumor invasion of the tectal plate and thalamus. The histologic examination confirmed the diagnosis of a low-grade oligodendroglioma. The patient then underwent chemotherapy and radiotherapy as adjuvant therapies. Conclusion Although the pineal region is a common place for a large number of tumoral lesions, low-grade oligodendrogliomas are extremely rare in this location. This case is only the second account of a benign oligodendroglioma of the pineal region reported in the literature.

Meningioma cordóide da região pineal / Pineal region chordoid meningioma

Objetivo: Meningiomas correspondem a apenas 8% dos tumores da região pineal. O meningioma cordóide (CM) representa0,5 a 1,0% de todos os meningiomas intracranianos, sendo ainda mais raro na região pineal. Na literatura, apenas seis casosde CMs são relatados. Apresentação clínica: Descrevemos o caso de um paciente com cefaleia, confusão mental, disartria eataxia de marcha. O exame oftalmológico revelou paresia do olhar vertical e dissociação do reflexo pupilar fotomotor e deconvergência. A RM revelou uma lesão expansiva na região da pineal com impregnação heterogênea pelo contraste. O tumorfoi totalmente ressecado pela abordagem occipital transtentorial lateral em posição três-quartos prona. A análise histológicarevelou um CM. Conclusão: Meningioma cordóide é uma variante rara de meningioma pouco descrita na região pineal, masque deve ser considerada como diagnóstico diferencial das patologias localizadas nessa região. Este estudo contribui para ummelhor entendimento do diagnostico e manejo destes tumores.

Multifocal intradural extramedullary ependymoma. Case report.

In this paper, the authors present the case of a patient with multifocal intradural extramedullary ependymoma, and they review 18 previously reported cases. A 32-year-old man presented to the authors' institution with a 1-month history of partial medullary syndrome. Magnetic resonance imaging of the neuraxis revealed multifocal intradural extramedullary lesions at the bulbomedullary junction and C2-3, T5-11, L-2, L-4, L-5, and sacrum. Histological examination revealed a WHO Grade II ependymoma. The literature survey yielded 18 cases of ependymoma at the same location; none of them were multifocal at presentation. The authors analyzed the epidemiological, clinical, and surgical features of all 19 cases reported to date, including the present case. Patients' ages ranged from 24 to 69 years; 15 patients were women and 4 were men. The time elapsed from symptom onset to diagnosis ranged from 1 month to 8 years. Pain (in 13 patients) and medullary syndrome (in 12) were reported as the initial symptoms (information was not provided for 1 patient). Tumors were predominantly located in the thoracic spine (11), but they also occurred in the cervicothoracic (3), cervical (2), and lumbar (2) spine. The remaining tumor was multifocal. Solitary extramedullary tumors were found intraoperatively in 13 patients; 3 were described as exophytic and 3 as extramedullary with some degree of medullary invasion. Histological examination revealed 9 WHO Grade II tumors, 4 Grade III tumors, and 1 myxopapillary tumor. Data obtained for the remaining cases proved inconclusive. The clinical condition improved in 11 patients, remained stable in 2, and worsened (recurrence or progression) in 6. Of the 4 patients with Grade II tumors who presented with recurrence or neuraxis spreading, 3 had meningeal infiltration or adhesion to the pia mater, which does not rule out the possibility of neoplastic remnants in that area. Intradural extramedullary ependymomas are rare, they predominate in women in the 5th decade of life, and pain is the most frequent initial symptom. The extent of resection and the presence of meningeal infiltration seem to be key determinants of prognosis. The present case is the first intradural extramedullary ependymoma (with the exception of those occurring at the conus medullaris and terminal filum) with multiple lesions at presentation.

Supra-orbital keyhole removal of anterior fossa and parasellar meningiomas.

The improvement of surgical techniques as well as the introduction of new surgical instruments promoted the use of keyhole craniotomies in neurosurgery. We evaluated the technical aspects of the supra-orbital keyhole approach considering the indications, limitations, and complications of this approach to treat anterior cranial fossa and parasellar meningiomas. Twenty-four patients (21 females; mean age, 53 + or - 8.6 years) operated on between 2002 and 2006 through a supra-orbital eyebrow approach were studied. Maximal tumor diameter ranged from 1.6 to 6 cm. Gross total resection was done in 20 (83.3%). All tumors were histologically benign. Two patients (8%) experienced CSF rinorhea and another two patients suffered transitory diabetes insipidus (8%). One patient experienced transitory hemiparesis. There was one case of meningitis and one mortality. Follow-up ranged between 6 to 66 months (mean 31.5 + or - 20.1 months), with no recurrence. The supra-orbital keyhole craniotomy is a useful minimally invasive approach to treat selected anterior fossa and parasellar meningiomas.

Supra-orbital keyhole removal of anterior fossa and parasellar meningiomas / Minicraniotomia supra-orbitária superciliar no tratamento de meningiomas na fossa craniana anterior e para-selares

The improvement of surgical techniques as well as the introduction of new surgical instruments promoted the use of keyhole craniotomies in neurosurgery. We evaluated the technical aspects of the supra-orbital keyhole approach considering the indications, limitations, and complications of this approach to treat anterior cranial fossa and parasellar meningiomas. Twenty-four patients (21 females; mean age, 53±8.6 years) operated on between 2002 and 2006 through a supra-orbital eyebrow approach were studied. Maximal tumor diameter ranged from 1.6 to 6 cm. Gross total resection was done in 20 (83.3 percent). All tumors were histologically benign. Two patients (8 percent) experienced CSF rinorhea and another two patients suffered transitory diabetes insipidus (8 percent). One patient experienced transitory hemiparesis. There was one case of meningitis and one mortality. Follow-up ranged between 6 to 66 months (mean 31.5±20.1 months), with no recurrence. The supra-orbital keyhole craniotomy is a useful minimally invasive approach to treat selected anterior fossa and parasellar meningiomas.

A evolução técnica e a introdução de instrumentais cirúrgicos mais delicados proporcionaram o uso de craniotomias menores no tratamento de patologias intracranianas. Avaliamos os aspectos técnicos da minicraniotomia supra-orbitária superciliar, considerando as indicações, limitações e complicações no tratamento de meningiomas na fossa craniana anterior e para-selares. Vinte e quarto pacientes (21 mulheres; idade média, 53±8,6 anos) operados entre 2002 e 2006 foram estudados. O diâmetro tumoral máximo variou de 1,6 a 6 cm. Ressecção total foi obtida em 20 (83,3 por cento). Todos os tumores eram histologicamente benignos. Dois pacientes (8 por cento) apresentaram fistula liquórica pós-operatória e outros dois diabetes insipido transitórioa (8 por cento). Um paciente evoluiu com hemiparesia transitória. Houve um caso de meningite e um de evolução fatal. O seguimento variou de 6 a 66 meses (média 31,5±20,1 meses), não houve recidiva. A minicraniotomia supra-orbitária superciliar é uma via de abordagem eficaz para o tratamento de meningiomas da fossa craniana anterior e para-selares selecionados.

Endonasal transsphenoidal surgery and multimodality treatment for giant pituitary adenomas.

OBJECTIVE: Giant pituitary adenomas (> or =40 mm) pose a major management challenge. We describe the experience of a single surgeon and a dedicated neuro-endocrine team with multimodality treatment of these tumours in three specialized institutions. DESIGN: Retrospective data set analyses. PATIENTS: Fifty-one consecutive patients with a giant adenoma (39 endocrine-inactive, 12 endocrine-active; mean tumour diameter 45 mm) treated over 10 years by an endonasal transsphenoidal approach were included. All patients had surgical resection followed by radiotherapy and/or medical therapy as judged necessary. MEASUREMENTS: Hormonal and visual status, extent of resection, tumour control rates, complications and use of medical and radiotherapy were evaluated. RESULTS: Surgery resulted in gross total, near total and subtotal removal in21 (41%), 10 (20%) and 20 (39%) patients respectively. Complete tumour removal was associated with absence of cavernous sinus invasion (P < 0.001). Long-term endocrine function improved in 49% of patients and new endocrinopathy occurred in 14.6%; 76% required long-term hormone replacement therapy. Vision improved in 81.5% of the patients and there was no visual worsening. At the last follow up (median 30 months), tumour control was achieved in 96% of patients: 59% with surgery alone, 20% with surgery plus focussed radiotherapy, 18% with surgery and medical therapy and two with all three modalities. CONCLUSIONS: Endonasal surgery provides effective initial treatment for patients with giant adenomas. Multimodality therapy was needed in almost 50% of patients and this rate will likely increase with longer follow up. Close collaboration of neurosurgeons with endocrinologists and radiation oncologists is essential for optimal treatment of patients with these challenging tumours.

[Anterior and lateral foramen magnum meningiomas]. / Meningiomas anteriores e antero-laterais do forame magno.

We report our experience with 11 cases of foramen magnum meningiomas, eight originating inside the posterior fossa and three in the caudal region. The mean age of the patients was 50.8 years and the main complaint was cervical headache for at least 18.6 months and at the neurological examination, tetraparesis and deficit of the lower cranial nerves were very often observed. All patients were submitted to surgical treatment, always with exposition of the vertebral artery at the entry zone in the dura mater of the posterior fossa, with partial removal of the occipital condyle in only three cases. Total resection was obtained in seven patients and partial removal in the other four due to adherences to vessels and nerves. The prognostic was related to the neurological condition before surgery.

Aggressive intracranial fibromatosis: case report.

UNLABELLED: Fibromatosis is a locally aggressive, proliferative fibroblastic lesion affecting musculoaponeurotic structures, most often in the limbs and trunk. Intracranial fibromatosis is extremely rare and requires aggressive treatment to prevent recurrence. CASE DESCRIPTION: We present the case of a 20 year old woman with aggressive skull base fibromatosis. The lesion extended through the sphenoid, ethmoid sinus and nasal cavity, destroying the right roof of the orbit and penetrating in anterior skull base. A combined anterior craniofacial approach was performed; complete resection with surgical margin was impossible due to the localization of the tumor and relation to important neurovascular structures. Complete resection with surgical margin is often impossible because of its widely infiltrative nature. Radiotherapy and chemotherapy are often required to improve local control of the lesion.

[Giant intracranial aneurysm in three years old boy: case report]. / Aneurisma intracraniano gigante em menino de três anos: relato de caso.

Cerebral aneurysms are rare in the pediatric age group and differ from adults' aneurysms in size, localization and incidence. We report a 3-year-old boy with giant middle cerebral artery aneurysms who presented with subarachnoid hemorrhage. The patient was submitted to surgical treatment and the postoperative period was uneventful.

Meningiomas anteriores e antero-laterais do forame magno / Anterior and lateral foramen magnum meningiomas

Relatamos nossa experiência com 11 pacientes portadores de meningiomas do forame magno, oito cranioespinhais e três espinocraniais. A média de idade foi 50,8 anos, o sintoma mais comum foi cefaléia occipital com duração média de 18,6 meses. Os principais achados neurológicos foram tetraparesia e comprometimento dos nervos cranianos baixos. O tratamento foi cirúrgico, sempre com exposição da artéria vertebral em sua entrada na dura-máter da fossa posterior e ressecção de parte do côndilo occipital apenas em três casos. Ressecção total foi possível em sete pacientes e parcial nos demais, devido às aderências a vasos e nervos. O prognóstico esteve relacionado com as condições neurológicas pré-operatórias.

Aggressive intracranial fibromatosis: case report

Fibromatose é lesão fibroblástica proliferativa com agressividade localizada, afetando as estruturas músculo-aponeuróticas e acometendo, mais freqüentemente, os membros e tronco. A fibromatose intracraniana é rara e requer tratamento agressivo para evitar recidiva. Descrevemos uma paciente de 20 anos portadora de fibromatose agressiva de base de crânio. A lesão se estendia através da cavidade nasal, seios esfenoidal e etmoidal, destruindo o teto da órbita direita e invadindo a porção anterior da base do crânio. A paciente foi submetida a uma via craniofacial anterior combinada, não sendo possível uma ressecção completa devido ao envolvimento de estruturas neurovasculares. A ressecção completa é, freqüentemente, impossível devido sua natureza infiltrativa. Radioterapia e quimioterapia são indicadas para melhorar o controle da lesão.

Aneurisma intracraniano gigante em menino de três anos: relato de caso / Giant intracranial aneurysm in three years old boy: case report

Aneurismas cerebrais são raros na faixa etária pediátrica. A apresentação destas lesões difere significativamente em relação á população adulta no que se refere a tamanho, localização e incidência. Relatamos caso de menimo de três anos de idade que apresentou quadro de hemorragia subaracnóidea sem história de infecções ou traumatismos prévios sendo, posteriormente, diagnosticado aneurisma gigante localizado na artéria cerebral média. Foi submetido a tratamento cirúrgico com boa evolução pós-operatória.