Topographic Patterns of Intracranial Meningioma Recurrences-Systematic Review with Clinical Implication.

BACKGROUND: While several risk factors for recurrences have been defined, the topographic pattern of meningioma recurrences after surgical resection has been scarcely investigated. The possibility of theoretically predicting the site of recurrence not only allows us to better understand the pathogenetic bases of the disease and consequently to drive the development of new targeted therapies, but also guides the decision-making process for treatment strategies and tailored follow-ups to decrease/prevent recurrence. METHODS: The authors performed a comprehensive and detailed systematic literature review of the EMBASE and MEDLINE electronic online databases regarding the topographic pattern of recurrence after surgical treatment for intracranial meningiomas. Demographics and histopathological, neuroradiological and treatment data, pertinent to the topography of recurrences, as well as time to recurrences, were extracted and analyzed. RESULTS: Four studies, including 164 cases of recurrences according to the inclusion criteria, were identified. All studies consider the possibility of recurrence at the previous dural site; three out of four, which are the most recent, consider 1 cm outside the previous dural margin to be the main limit to distinguish recurrences closer to the previous site from those more distant. Recurrences mainly occur within or close to the surgical bed; higher values of proliferation index are associated with recurrences close to the original site rather than within it. CONCLUSIONS: Further studies, including genomic characterization of different patterns of recurrence, will better clarify the main features affecting the topography of recurrences. A comparison between topographic classifications of intracranial meningioma recurrences after surgery and after radiation treatment could provide further interesting information.

Single versus multiple reoperations for recurrent intracranial meningiomas.

PURPOSE: To identify the risk factors and management of the multiple recurrences and reoperations for intracranial meningiomas. METHODS: Data of a neurosurgical series of 35 patients reoperated on for recurrent intracranial meningiomas were reviewed. Analyzed factors include patient age and sex, tumor location, extent of resection, WHO grade, Ki67-MIB1 and PR expression at initial diagnosis, time to recurrence; pattern of regrowth, extent of resection, WHO grade and Ki67-MIB1 at first recurrence were also analyzed. All these factors were stratified into two groups based on single (Group A) and multiple reoperations (Group B). RESULTS: Twenty-four patients (69%) belonged to group A and 11 (31%) to group B. The age < 65 years, male sex, incomplete resection at both initial surgery and first reoperation, and multicentric-diffuse pattern of regrowth at first recurrence are risk factors for multiple recurrences and reoperations. In group B, the WHO grade and Ki67-MIB1 increased in further recurrences in 54% and 64%, respectively. The time to recurrence was short in 7 cases (64%), whereas 4 patients (36%) further recurred after many years. Eight patients (73%) are still alive after 7 to 22 years and 2 to 4 reoperations. CONCLUSION: The extent of resection and the multicentric-diffuse pattern of regrowth at first recurrence are the main risk factors for multiple recurrences and reoperations. Repeated reoperations might be considered even in patients with extensive recurrent tumors before the anaplastic transformation occurs. In such cases, even partial tumor resections followed by radiation therapy may allow long survival in good clinical conditions.

Time to Recurrence of Intracranial Meningiomas from a Monoinstitutional Surgical Series.

BACKGROUND: Meningiomas show variable tendency to recur. While risk factors of recurrence have been largely investigated in literature, a paucity of data is available on the time to recurrence. Our purpose was to identify main factors affecting the time to recurrence to assist preoperative treatment decision-making strategy and to define a tailored clinical and neuroradiological follow-up. METHODS: Data of 35 patients with intracranial meningioma recurrences have been retrospectively reviewed. Demographic (patient age at initial diagnosis and sex), radiologic (meningioma location, pattern of regrowth and topography of recurrences at first reoperation), pathologic (WHO grade and Ki67-MIB1 at initial surgery and at first reoperation, progesterone receptor [PR] expression), and surgical (extent of resection at initial surgery according to Simpsons grading system, number of reoperations) factors were analyzed. RESULTS: Time to recurrence ranged from 20 to 120 months. Extent of resection at initial surgery was Simpson grade I in 7 patients (20%), grade II in 10 (28.5%), grade III in 14 (40%), and grade IV in 4 (11.5%). Longer median time to recurrence was observed for skull base localization (P < 0.01), Simpson grades I and II versus grades III (P = 0.01) and IV (P = 0.02), values of Ki67-MIB1 ≤ 4% (P = 0.001), and PR > 60% (P = 0.03); conversely, sex, age, number of reoperations, unchanged/progression of Ki67, and/or World Health Organization grade between first surgery and reoperation did not correlate in statistically significant way with time to recurrence. CONCLUSIONS: The extent of resection and the Ki67-MIB1 represent the most important factors predicting shorter recurrence time of intracranial meningiomas. Patients with incomplete (Simpson grades III and IV) resection and high Ki67-MIB1 values, especially at non-skull base localization and with low PR values, require a closer short-term clinical and radiologic follow-up in the first years after surgery.

Atypical Teratoid/Rhabdoid Tumor of the Nervous System in Adults: Location-Related Features and Outcome.

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) of the nervous system is a rare and highly malignant neoplasm, mainly affecting children, first recognized as a pathologic entity in 1996 and added to the World Health Organization Classification of the Tumors of the Central Nervous System in 2000. AT/RT is even rarer among adults and is associated with a worse prognosis. The aim of the present study was to analyze the different tumor features according to the location in adults. METHODS: A comprehensive and detailed literature review of AT/RTs in adults was made. The demographic, management, and outcome data associated with tumor location were analyzed and compared; histopathologic and molecular features were also discussed. Furthermore, we added our personal case with brain hemispheric localization and reported a progression-free survival of 103 months after gross total resection and adjuvant radiotherapy showing a peculiar histopathologic pattern. RESULTS: Female sex is mainly affected by AT/RT on median localizations, both intracranial and spinal, and by all sellar region cases. Gross total resection is mainly achieved among lateral compared with median localizations. Combined radiotherapy and chemotherapy is the most adopted adjuvant treatment in all tumor localizations and is related to better outcome. Postoperative death is reported only among sellar region localizations, whereas brain hemispheric cases show the best overall survival. CONCLUSIONS: AT/RTs show different and peculiar features according to their location, which significantly affects the outcome; precise knowledge of them helps the neurosurgeon in planning the best strategy for treatment.

Update on the Diagnosis and Management of Meningiomas.

This series of five articles (one original article and four reviews) focuses on the most recent and interesting research studies on the biomolecular and radiological diagnosis and the surgical and medical management of meningiomas [...].

Meningiomas of the rolandic region: risk factors for motor deficit and role of intra-operative monitoring.

OBJECTIVE: Meningiomas of the rolandic region are associated to high risk of postoperative motor deficits. This study discusses the factors affecting motor outcome and recurrences from the analysis of a monoinstitutional case series and eight studies from a literature review. METHODS: Data of 75 patients who underwent surgery for meningioma of the rolandic region were retrospectively reviewed. The analyzed factors included tumor location and size, clinical presentation, magnetic resonance imaging (MRI) and surgical findings, brain-tumor interface, extent of resection, postoperative outcome and recurrence. Eight studies from literature on rolandic meningiomas treated with or without intraoperative monitoring (IOM) were reviewed with the aim to define the impact of IOM on the extent of resection and motor outcome. RESULTS: Among the 75 patients of the personal series, the meningioma was on the brain convexity in 34 (46%), at the parasagittal region in 28 (37%) and at the falx in 13 (17%). The brain-tumor interface was preserved in 53 cases (71%) at MRI and in 56 (75%) at surgical exploration. Simpson grade I resection was obtained in 43% of patients, grade II in 33%, grade III in 15% and grade IV in 9%. The motor function worsened postoperatively in 9 among 32 cases with preoperative deficit (28%) and in 5 among 43 with no preoperative deficit (11.5%); definitive motor deficit was evidenced in overall series at follow-up in 7 (9.3%). Patients with meningioma with lost arachnoid interface had significant higher rates of worsened postoperative motor deficit (p = 0.01) and seizures (p = 0.033). Recurrence occurred in 8 patients (11%). The analysis of the 8 reviewed studies (4 with and 4 without IOM) shows in the group without IOM higher rates of Simpson grades I and II resection (p = 0.02) and lower rates of grades IV resection (p = 0.002); no significant differences in postoperative immediate and long-term motor deficits were evidenced between the two groups. CONCLUSIONS: Data from literature review show that the use of IOM does not affect the postoperative motor deficit Therefore, its role in rolandic meningiomas resection remains to be determined and will be defined in further studies.

Cervical epidural abscess complicated by a pharyngoesophageal perforation after anterior cervical spine surgery for subaxial spondylodiscitis.

Background: The anterior approach to the cervical spine is safe and effective, but not without risks. The pharyngoesophageal perforation (PEP) is a rare but potentially life-threatening complication of this surgical route. A prompt diagnosis and adequate treatment are crucial for the prognosis; nevertheless, there is no unique consent about the best management. Case Description: A 47-year-old woman was referred to our neurosurgical unit for clinical and neuroradiological signs of multilevel cervical spine spondylodiscitis, which was conservatively treated with long-term antibiotic therapy and cervical immobilization after computed tomography-guided biopsy. Nine months later, when the infection was resolved, the patient underwent C3-C6 spinal fusion with anterior plate and screws through anterior approach to the cervical spine for degenerative vertebral changes causing severe myelopathy, and C5- C6 retrolisthesis with instability. Five days after surgical procedure, the patient developed a pharyngoesophageal-cutaneous fistula, detected through wound drainage, and confirmed by swallowing contrast study, without systemic signs of infection. The PEP was conservatively treated, with antibiotic therapy and parenteral nutrition, and it was monitored through seriate swallowing contrast and magnetic resonance studies up to the complete resolution. Conclusion: The PEP is a potentially fatal complication of the anterior cervical spine surgery. We suggest an accurate intraoperative control of the pharyngoesophageal's tract integrity at the end of the surgical procedure and a longtime follow-up, because the risk of occurrence is up to several years after surgery.

Intracranial Meningiomas in Patients Aged ≥80 Years: Pathological Features and Surgical Problems.

BACKGROUND: Patients aged >80 years frequently have intracranial meningiomas. In the present study, we have discussed the pathological features, comorbidities, and surgical complications for this age group from a surgical series and literature review. METHODS: In the present study, we reviewed a surgical series of 354 intracranial meningiomas and compared the oldest age group (age, ≥80 years) of 17 patients with 73 patients aged 70-79 years and 264 patients aged <70 years. From a literature review, we selected 10 studies of meningiomas in patients aged ≥80 years. The analyzed factors included sex, meningioma location, World Health Organization grade, Ki-67 MIB1, progesterone receptor expression, comorbidities, American Society of Anesthesiologists class, Karnofsky performance scale score, postoperative complications, and death. RESULTS: Patients aged ≥80 years had had higher rates of World Health Organization grade II meningioma, higher rates of Ki-67 expression of >4% and <20%, and progesterone receptor expression <15%. Of the postoperative complications, only neurological deficits and acute bronchopneumonia were significantly more frequent in patients aged ≥80 years. The incidence of intracerebral hematoma, lung embolism, acute heart ischemia, and death were not significantly different between the patients aged ≥80 years and those aged 70-79 years and <70 years. CONCLUSIONS: Patients aged ≥80 years must be considered a true elderly group with higher rates of comorbidities. The very old age is not a limitation to surgery; however, careful patient selection is necessary. In addition, for the oldest age group, the surgical decision should not be delayed because of advancing age.

Management of the skull base invasion in spheno-orbital meningiomas.

BACKGROUND: The tumor invasion of the skull base structures is very frequent in spheno-orbital meningiomas. The aim of the present study is to evaluate the invasion rate of skull base structures and the best surgical approach and management. METHODS: The surgical series of 80 spheno-orbital meningiomas was reviewed. The tumors were classified according to the intraorbital location with respect to the optic nerve axes into three types: I-lateral: II-medial; III-diffuse. The invasion of the orbital apex, optic canal, superior orbital fissure, anterior clinoid, ethmoid-sphenoid sinuses, and infratemporal fossa was evaluated. The rate and extension of involvement of these structures was correlated with the intraorbital location and the surgical approach. The preoperative ophtalmological symptoms and signs and their outcome were also evaluated. RESULTS: Proptosis was found in 79 patients (97%), variable decrease of the visual function in 47 patients (59%), and deficits of the eye movements in 28(35%). The invasion of the optic canal (74%), superior orbital fissure (65%), anterior clinoid (60%), and orbital apex (59%) was more frequently found, whereas the tumor extension into the ethmoid-sphenoid sinuses (4%) and infratemporal fossa (4%) was rare. Types II and III meningiomas showed significantly higher involvement of the skull base structures than type I ones, which only had 15% invasion of the optic canal. Remission or significant improvement of the visual function occurred postoperatively in 24 among 47 cases (51%), with a higher rate for type I meningiomas vs. other types (p = 0.021, p = 0.019) and worsening in 7 (15%). CONCLUSIONS: Spheno-orbital meningiomas growing in the lateral orbital compartment show no involvement of the skull base structures excepting the optic canal as compared to those growing medially or diffusely. The surgical resection of tumor invading the skull base structures should be more extensive as possible, but the risk of optic and oculomotor deficits must be avoided.

Regorafenib beyond the Second Line in Relapsed Glioblastoma: A Case Report and Literature Review.

Glioblastoma multiforme (GBM) is one of the most frequent and aggressive primary tumors in the central nervous system, representing more than 60% of all brain tumors in adults. Primary GBM remains incurable with a poor prognosis both for limited therapeutic alternatives and for a high risk of progression or recurrence. In fact, at recurrence, the few treatment options available, and often characterized by limited effectiveness, have always been an Achilles' heel. The recent approval of second line of regorafenib, a multikinase inhibitor, has given hope after several years of darkness for new therapies in the treatment of GBM. Indeed, in the REGOMA trial, a phase 2 study, regorafenib was the first drug to show a statistically significant improvement in median overall survival compared with lomustine group, usually used in the second-line treatment after temozolomide failure. We report a case of a 43-year-old patient affected by GBM in treatment with regorafenib in third line of therapy with good disease control and long PFS.

Brain Gliomas and Ollier Disease: Molecular Findings as Predictive Risk Factors?

Background: Ollier disease (OD) is a rare nonhereditary type of dyschondroplasia characterized by multiple enchondromas, with typical onset in the first decade of life. Surgery is the only curative treatment for primary disease and its complications. Patients with OD are at risk of malignant transformation of enchondromas and of occurrence of other neoplasms. Methods: A wide literature review disclosed thirty cases of glioma associated with OD, most of them belonging to the pre-molecular era. Our own case was also included. Demographic, clinical, pathologic, molecular, management, and outcome data were analyzed and compared to those of sporadic gliomas. Results: Gliomas associated with OD more frequently occur at younger age, present higher rates of multicentric lesions (49%), brainstem localizations (29%), and significantly lower rates of glioblastomas (7%) histotype. The IDH1 R132H mutation was detected in 80% of gliomas of OD patients and simultaneously in enchondromas and gliomas in 100% of cases. Conclusions: The molecular data suggest a higher risk of occurrence of glioma in patients with enchondromas harboring the IDH1 R132H mutation than those with the IDH1 R132C mutation. Thus, we suggest considering the IDH1 R132H mutation in enchondromas of patients with OD as a predictive risk factor of occurrence of glioma.

Spinal cervical extradural hemangioblastoma.

Spinal cervical extradural and intra-extradural hemangioblastomas are exceptional, with only nine reported cases. This study reviews the diagnostic and surgical problems of this rare entity. Two female patients, aged 80 years and 25 years, respectively, one with Von Hippel-Lindau disease (VHLD), experienced brachial pain and weakness. On magnetic resonance imaging, a dumbbell intra-extraspinal hemangioblastoma was evidenced. The surgical resection through posterior laminectomy resulted in clinical remission of brachial pain and weakness. The magnetic resonance aspect of a dumbbell lesion suggests a neurogenic tumor; the correct preoperative diagnosis is possible in individuals with VHLD. The surgical problems include high tumor vascularity, vertebral artery control, and nerve root preservation. However, the surgical excision results in clinical remission.

Recurrences of Spheno-Orbital Meningiomas: Risk Factors and Management.

BACKGROUND: The extent of resection constitutes one of the most important predictive risk factors of recurrence for spheno-orbital meningiomas; although gross total resection represents the gold standard, it is not always achievable, with a consequent high rate of recurrence. Management of these tumors is a surgical challenge and is represented by maximal safe resection with preservation of function. The aim of the present study is to discuss the risk factors for recurrence and the best management of the recurrent tumors. METHODS: Eighty patients operated on for spheno-orbital meningiomas were retrospectively reviewed. Two groups were identified: group 1 comprised 30 patients (37.5%) who experienced recurrence and group 2 comprised 50 patients with no recurrence from 5 to 28 years after the initial surgery. The analyzed factors in both groups include the involvement of the skull base structures, the extent of resection, and World Health Organization grade. In the recurrence group, the pattern of tumor regrowth, the entity of resection, and the management were also analyzed. RESULTS: The invasion of the whole orbit, the involvement of the orbital apex, superior orbital fissure, infratemporal fossa, and sphenoidal-ethmoidal sinuses, and World Health Organization grade II are risk factors of recurrence. All 30 patients with recurrence underwent reoperation, 9 of whom had 2 or 3 reoperations. Overall, 70 of the 80 patients (88%) had tumor control and no progression after one or more reoperations. CONCLUSIONS: We suggest re-surgery for spheno-orbital meningioma recurrences to prevent worsening of visual function and proptosis. Because of their slow natural course, even multiple reoperations may be performed, resulting in long overall survival with stable symptoms and good quality of life.

The Role of Surgery in Spinal Intradural Metastases from Renal Cell Carcinoma: A Literature Review.

BACKGROUND: Due to the few reported cases of spinal intradural metastases from renal cell carcinoma (RCC), there is no unanimous consensus on the best treatment strategy, including the role of surgery. METHODS: A wide and accurate literature review up to January 2022 has disclosed only 51 cases of spinal intradural metastases from RCC. Patients with extramedullary (19) and those with intramedullary (32) localization have been separately considered and compared. Demographics, clinical, pathological, management, and outcome features have been analyzed. RESULTS: Extramedullary lesions more frequently showed the involvement of the lumbar spine, low back pain, and solitary metastasis at diagnosis. Conversely, the intramedullary lesions were most often detected in association with multiple localizations of disease, mainly in the brain. Surgery resulted in improvement of clinical symptoms in both groups. CONCLUSION: Several factors affect the prognosis of metastatic RCC. The surgical removal of spinal metastases resulted in pain relief and the arresting of neurological deficit progression, improving the quality of life and overall survival of the patient. Considering the relative radioresistant nature of the RCC, the surgical treatment of the metastasis is a valid option even if it is subtotal, with a consequent increased risk of recurrence, and/or a nerve root should be sacrificed.

Gliosarcoma with direct involvement of the oculomotor nerve: Case report and literature review.

Gliosarcoma is a rare malignant brain tumor, characterized by a biphasic tissue pattern with alternating areas displaying glial and mesenchymal differentiation. We first report a case of temporo-mesial gliosarcoma, extended to the crural and ambient cisterns, with direct involvement of the ipsilateral third cranial nerve and encasement of anterior choroidal, posterior communicant and posterior cerebral arteries, presenting without symptoms of peripheral neuropathy. A 61-year-old woman with 1-month history of intense bilateral frontal-temporal headache resistant to pharmacological therapy and paresis of the left lower midface underwent surgical resection, through pterional trans-sylvian approach, of a right temporo-mesial gliosarcoma which directly involved the ipsilateral oculomotor nerve. Reported cases of gliomas with direct involvement of a cranial nerve, from the third to the twelfth, are very rare, whit no cases of gliosarcoma described. Because of its rarity, sometimes this entity is not considered as diagnostic hypothesis and is misdiagnosed, both during preoperative diagnostic evaluation and during the surgery. Gliosarcoma is a strong challenge for neurosurgeons and neurooncologists because of low incidence, poor prognosis and limited reported cases on literature. This case shows unique features for localization, pattern of growth and clinical presentation.

Microsurgical repair by autografting in traumatic injuries of peripheral nerves.

BACKGROUND: Peripheral nerve injuries (PNI) with traumatic origin in upper and lower extremities are pathologies with an important quality-of-life considerations. For neurosurgeons, it is mandatory to understand their physiopathological mechanism and a proper treatment. The authors describe a series of 50 patients with traumatic PNI who underwent microsurgical reconstruction by autologous graft between 1993 and 2014. METHODS: Patients aged less than 65, who had neurological deficit in a range 3-12 months and severe and persistent nerve injury at electrophysiological examination were included in the study. After grafting, the overall functional recovery of the neurological deficit, the main prognostic factors (age, injured nerve, damage mechanism, gap length and surgical timing) and the postoperative functional outcome were analyzed. Neurological and electrophysiological follow-up was at 6-/12-/24-/48 months after surgery. RESULTS: The results showed that the best neurological recovery can be found in young patients with cut injuries of the upper limbs and that the outcome mainly depends on involved nerve, lesion type and minimum gap length. Moreover, follow-up for these pathologies should last till 48 months. CONCLUSIONS: In the future, these results could be further improved by the rising new techniques of nerve repair and the advances in neurobiology.

Malignant intraventricular meningioma: literature review and case report.

Malignant intraventricular meningiomas (IVMs) are very rare with only a few reported cases. A midline search up to December 2020 selected 40 articles for a total of 65 patients. The inclusion criteria were series and case reports in English language, as well as papers written in other languages, but with abstracts written in English. Malignant IVMs at the first diagnosis (group A, 50 patients) and those with anaplastic transformation from previous WHO grades I and II tumors (group B, 15 patients) were separately analyzed. The unique personal case among 1285 meningiomas (0.078%) is also added. Malignant IVMs mainly occur in women (61%) with a median age of 45 years and are mainly located in the lateral ventricle (93%) and trigonal region (74%), with no cases in the fourth ventricle. Irregular borders (80%), heterogeneous enhancement (83%), and perilesional edema (76%) are the most frequent radiological findings. The histology was mainly pure anaplastic (85%), whereas papillary (7%), rhabdoid (5%), and mixed forms (3%) are very rare. The CSF spread was found in 60% of the cases. The prognosis is very dismal, with an overall median survival of 17.5 months after surgery for the anaplastic forms. Malignant IVMs at initial diagnosis (group A) show better overall survival (25 months) than those occurring from anaplastic transformation of lower grade tumors (group B) (10.1 months).

Meningioma during pregnancy: what can influence the management? A case series and review of the literature.

Purpose: Meningioma is a benign tumor, more frequent in female population. During pregnancy, distinguishing a meningioma from other common conditions presenting with similar symptoms (headache, vomiting, visual impairment) is challenging. Moreover, the management must consider not only maternal but also fetal health. The rarity of the condition does not allow to define the features to which look in order to stratify the risk for the need of surgery during pregnancy. We reported three cases of meningioma in pregnant women treated at our department and reviewed those previously reported in the literature. The aim of this review is to evaluate which factors are more determinant in such management.Methods: Electronic databases were searched from year 2000 until June 2020, to identify clinical studies on management of meningioma diagnosed during pregnancy. The primary outcome was surgical timing. Secondary outcomes were delivery methods, maternal and neonatal outcomes.Results: Surgery after pregnancy is more frequently performed in PR + tumor (p-value 0.038) and with HA (p-value 0.0445), as well as in meningioma diagnosed during the third trimester, compared to those diagnosed before (p-value 0.0012). Surgery during pregnancy was more frequent in patients with visual loss (p-value 0.006). No significant differences were found in surgical management, according to age, WHO grade, tumor location, lesion diameter and ER positivity. Delivery method is independent from both hormonal receptor status and main symptoms, but women who had neurosurgery during pregnancy delivered more frequently with spontaneous vaginal delivery (p-value <0.01).Conclusion: The decision regarding surgical timing of meningioma diagnosed during pregnancy depends on PR + and impending symptoms as visual loss or headache. It seems that timing of neurosurgery does not affect the delivery method. A multidisciplinary approach is always useful to perform a rapid and appropriate diagnosis and to better evaluate pros and cons of surgery during pregnancy and following management both for maternal and fetal wellness.