Efficacy of radiotherapy and stereotactic radiosurgery as adjuvant or salvage treatment in atypical and anaplastic (WHO grade II and III) meningiomas: a systematic review and meta-analysis.

The role of radiotherapy (RT) and stereotactic radiosurgery (SRS) as adjuvant or salvage treatment in high-grade meningiomas (HGM) is still debated. Despite advances in modern neuro-oncology, HGM (WHO grade II and III) remains refractory to multimodal therapies. Published reports present aggregated data and are extremely varied in population size, exclusion criteria, selection bias, and inclusion of mixed histologic grades, making it extremely difficult to draw conclusions when taken individually. This current work aims to gather the existing evidence on RT and SRS as adjuvants following surgery or salvage treatment at recurrence after multimodality therapy failure and to conduct a systematic comparison between these two modalities. An extensive systematic literature review and meta-analysis were performed. A total of 42 papers were eligible for final analysis (RT n = 27; SRS n = 15) after searching MEDLINE via PubMed, Web-of-science, Cochrane Wiley, and Embase databases. Adjuvant regimens were addressed in 37 papers (RT n = 26; SRS n = 11); salvage regimens were described in 5 articles (RT n = 1; SRS n = 4). The primary outcomes of the study were the overall recurrence rate and mortality. Other actuarial rates (local and distant control, OS, PFS, and complications) were retrieved and analyzed as secondary outcomes. A total of 2853 patients harboring 3077 HGM were included. The majority were grade II (87%) with a mean pre-radiation volume of 8.7 cc. Adjuvant regimen: 2742 patients (76.4% RT; 23.6% SRS) with an overall grade II/III rate of 6.6/1. Lesions treated adjSRS were more frequently grade III (17 vs 12%, p < 0.001), and received subtotal resection (57 vs 27%, p = 0.001) compared to the RT cohort. AdjSRS cohort had a significantly shorter mean follow-up than adjRT (36.7 vs 50.3 months, p = 0.01). The overall recurrence rate was 38% in adjRT vs 25% in adjSRS (p = 0.01), while mortality did not differ between the groups (20% vs 23%, respectively; p = 0.80). The median time to recurrence was 1.5 times longer in the RT group (p = 0.30). Five-year local control was 55% in adjRT and 26% in adjSRS (p = 0.01), while 5-year OS was 73% and 78% (p = 0.62), and 5-year PFS was 62% and 40% in adjRT and adjSRS (p = 0.008). No difference in the incidence of complications (24% vs 14%, p = 0.53). Salvage regimen: 110 patients (37.3% RT; 62.7% SRS) with a grade II/III rate of 8.6/1. The recurrence rate was 46% in salRT vs 24% in salSRS (p = 0.39), time to recurrence was 1.8 times longer in the salRT group (35 vs 18.5 months, p = 0.74). Mortality was slightly yet not significantly higher in salRT (34% vs 12%, p = 0.54). Data on local and distant control were only available for salSRS. The 5-year OS was 49% and 83% (p = 0.90), and the 5-year PFS was 39% and 50% in salRT and salSRS (p = 0.66), respectively. High-grade meningiomas (WHO grade II and III) receiving adjuvant RT showed a higher overall recurrence rate than meningiomas receiving adjuvant SRS. The adjRT cohort, however, achieved higher 5-year LC and PFS rates, thus suggesting a potentially longer time to recurrence compared to adjSRS patients, who, meanwhile, experienced a significantly shorter follow-up. This result must also consider the higher number of grade III lesions and the smaller extent of resection achieved in the adjSRS group. Overall mortality did not differ between the two groups. No differences in outcome measures were observed in salvage regimens.

History of Evolution of Posterolateral Approaches to the Thoracic Spine: From Cure of Pott's Disease to Epidural Tumor Resection.

Since the end of the nineteenth century, the wide dissemination of Pott's disease has ignited debates about which should be the ideal route to perform ventrolateral decompression of the dorsal spine in case of paraplegia due to spinal cord compression in tuberculosis spondylitis. It was immediately clear that the optimal approach should be the one minimizing the surgical manipulation on both neural and extraneural structures while optimizing the exposure and surgical maneuverability on the target area. The first attempt was reported by Victor Auguste Menard in 1894, who described, for the first time, a completely different route from traditional laminectomy, called costotransversectomy. The technique was conceived to drain tubercular paravertebral abscesses causing paraplegia without manipulating the spinal cord. Over the following decades, many other routes have been described all over the world, thus demonstrating the wide interest on the topic. Surgical development has been marked by the new technical achievements and by instrumental/technological advancements, until the advent of portal surgery and endoscopy-assisted techniques. In this article, the authors retraced the milestones of this history up to the present days, through a systematic review on the topic.

Comparison between inferior frontal gyrus intrinsic connectivity network and verb-generation task fMRI network for presurgical language mapping in healthy controls and in glioma patients.

Task-based functional MRI (tb-fMRI) represents an extremely valuable approach for the identification of language eloquent regions for presurgical mapping in patients with brain tumors. However, its routinely application is limited by patient-related factors, such as cognitive disability and difficulty in coping with long-time acquisitions, and by technical factors, such as lack of equipment availability for stimuli delivery. Resting-state fMRI (rs-fMRI) instead, allows the identification of distinct language networks in a 10-min acquisition without the need of performing active tasks and using specific equipment. Therefore, to test the feasibility of rs-fMRI as a preoperative mapping tool, we reconstructed a lexico-semantic intrinsic connectivity network (ICN) in healthy controls (HC) and in a case series of patients with gliomas and compared the organization of this language network with the one derived from tb-fMRI in the patient's group. We studied three patients with extra-frontal gliomas who underwent functional mapping with auditory verb-generation (AVG) task and rs-fMRI with a seed in the left inferior frontal gyrus (IFG). First, we identified the functional connected areas to the IFG in HC. We qualitatively compared these areas with those that showed functional activation in AVG task derived from Neurosynth meta-analysis. Last, in each patient we performed single-subject analyses both for rs- and tb-fMRI, and we evaluated the spatial overlap between the two approaches. In HC, the IFG-ICN network showed a predominant left fronto-temporal functional connectivity in regions overlapping with the AVG network derived from a meta-analysis. In two patients, rs- and tb-fMRI showed comparable patterns of activation in left fronto-temporal regions, with different levels of contralateral activations. The third patient could not accomplish the AVG task and thus it was not possible to make any comparison with the ICN. However, in this patient, task-free approach disclosed a consistent network of fronto-temporal regions as in HC, and additional parietal regions. Our preliminary findings support the value of rs-fMRI approach for presurgical mapping, particularly for identifying left fronto-temporal core language-related areas in glioma patients. In a preoperative setting, rs-fMRI approach could represent a powerful tool for the identification of eloquent language areas, especially in patients with language or cognitive impairments.

Pediatric cerebellar pilocytic astrocytoma presenting with spontaneous intratumoral hemorrhage.

Pilocytic astrocytomas (PAs) are benign glial tumors and one of the most common childhood posterior fossa tumors. Spontaneous intratumoral hemorrhage in PAs occurs occasionally, in about 8-20% of cases. Cerebellar hemorrhages in pediatric population are rare and mainly due to head injuries, rupture of vascular malformations, infections, or hematological diseases. We have investigated the still controversial and unclear pathophysiology underlying intratumoral hemorrhage in PAs. Bleeding in low-grade tumors might be related to structural abnormalities and specific angio-architecture of tumor vessels, such as degenerative mural hyalinization, "glomeruloid" endothelial proliferation, presence of encased micro-aneurysms, and glioma-induced neoangiogenesis. The acute hemorrhagic presentation of cerebellar PA in childhood although extremely uncommon is of critical clinical importance and necessitates promptly treatment. We described a case of hemorrhagic cerebellar PA in a 9-year-old child and reviewed the English-language literature that reported spontaneous hemorrhagic histologically proven cerebellar PA in pediatric patients (0-18 years). According to our analysis, the mortality was not related to symptom onset, tumor location, hemorrhage distribution, presence of acute hydrocephalous, and timing of surgery, while the GCS at hospital admission resulted to be the only statistically significant prognostic factor affecting survival outcome. The abrupt onset of signs and symptoms of acute hydrocephalous and consequent raised intracranial pressure are life-threatening conditions, which need emergent medical and neurosurgical treatments. At a later time, the identification of posterior fossa hemorrhage etiology is crucial to select the appropriate treatment and address the surgical strategy, optimizing the postoperative results.

Sublabial transsphenoidal microsurgical technique to treat congenital transsphenoidal encephalocele: a technical note.

Encephalocele is a rare malformation consisting in herniation of cranial contents through a cranial defect. A transsphenoidal location is uncommon, representing 5% of all basal encephaloceles. The surgical treatment of transsphenoidal encephaloceles is challenging. An optimal approach has not yet been determined, and it varies according to the surgical experience. We report the surgical management of a transsphenoidal encephalocele. The encephalocele and the sellar defect were repaired through a sublabial transsphenoidal microsurgical approach (TSM). Preoperative magnetic resonance imaging (MRI) and computed tomography (CT) scans were crucial for surgical planning. The sublabial transsphenoidal microsurgical approach offered a good and complete exposure of both the sac and the bone defect. Therefore, the congenital defect was successfully repaired with complete resolution of the encephalocele without any surgical or medical complications. Postoperative CT scan and MRI showed the restoration of the bone defect and the recovery of a normal anatomy with herniated structures pushed back into the sella. The described sublabial transsphenoidal microsurgical approach represents a minimally invasive, safe, and effective treatment strategy for transsphenoidal encephalocele.

Radiosurgical treatment of arteriovenous malformations in a retrospective study group of 33 children: the importance of radiobiological scores.

PURPOSE: Arteriovenous malformations' (AVMs) obliteration depends on several factors; among the many factors that must be considered to obtain a high rate of obliteration and a low rate of complications, Flickinger-Pollock Score (FPS) seems to have an important role but still have to be validated in the pediatric population while Paddick-Conformity Index (PCI) still has no demonstration of its utility on the outcome and is considered only as a treatment quality marker. METHODS: We retrospectively analyzed 33 consecutive children (2-18 years) with an AVM, treated with stereotactic radiosurgery Gamma Knife (SRS-GK) from 2001 to 2014 in our institution. We assess angiographic (DSA) Obliteration Rate (OR) as well FPS and PCI to draw conclusions. RESULTS: DSA-OR was 60.6% with a rate of hemorrhage of 0%. median target volume (TV) was 3.60 cc (mean 4.32 ± 3.63; range 0.15-14.2), median PD was 22 Gy (mean 21.4 ± 2.6; range 16.5-25). Median percentage of coverage was 98% (mean 97 ± 3; range 84-100). The median modified FPS was 0.78 (mean 0.89 ± 0.52; range 0.21-2.1) and highly correlate with OR (p = 0.01). The median PCI was 0.65 (mean 0.65 ± 0.14; range 0.34-0.95) A PCI lower than 0.57 highly correlates with final OR (p = 0.02). CONCLUSION: SRS-GK was safe and gradually effective in children. A prescription dose-like that used in adult population (i.e. > 18 and between 20 and 25 Gy) is essential to achieve obliteration. A PD of 23 Gy and 22 Gy did impact OR, respectively (p = 0.02) and (p = 0.05). FPS and PCI are valuable scores that seem to correlate with the OR also in the pediatric population although further prospective studies are needed to confirm these observations.

Usefulness of Ultrasound-Guided Microsurgery in Cavernous Angioma Removal.

BACKGROUND: Primary elements of surgical treatment of cavernous angiomas (CAs) are precise lesion identification and optimal trajectory determination. Navigation techniques allow for better results compared to microsurgery alone. In this study, we examined the benefits of intraoperative ultrasound (IOUS) use as an adjunct to standard localization systems. METHODS: We retrospectively analyzed 59 CAs, comparing outcomes in 2 groups of patients: 34 who underwent frame-based or frameless navigation-assisted microsurgery (no-IOUS group) and 25 who underwent IOUS-guided microsurgery associated with these techniques (IOUS group). RESULTS: The use of IOUS did not significantly increase the surgery time (mean, 172 ± 1.7 minutes in the IOUS group and 192.6 ± 11.5 in no-IOUS group; P = 0.08). In all 25 patients in the IOUS group, IOUS allowed for ready identification of CA as a hyperechoic mass. At the last follow-up (mean, 41.7 ± 3.5 months postsurgery), 95.2% of the IOUS group and 80.8% of the no-IOUS group had a modified Rankin Scale score of 0-1 and an Extended Glasgow Outcome Scale score of 7-8 (P = 0.2), with 100% and 64%, respectively, included in Engel outcome scale class IA (P = 0.006). Complete removal, as confirmed on postoperative magnetic resonance imaging, was achieved in all patients in the IOUS group and in almost all (97.1%; P = 0.4) patients in the no-IOUS group. CONCLUSIONS: IOUS is a valid tool for the intraoperative identification of CAs. Implementation of standard localization methods with IOUS guidance was associated with complete resection in all cases, without increasing surgical time. Compared with microsurgery without IOUS guidance, long-term functional outcomes showed better trends, and the epilepsy-free rate was significantly higher.

Cyst-cisternal shunting for cystic multirecurrent brainstem epidermoid: case report and literature review.

BACKGROUND: Surgical treatment of recurrent, posterior cranial fossa epidermoids in multioperated patients carries significant morbidity, mainly due to tumor adhesion to cranial nerves and vessels, and brainstem involvement. Radical resection is often not feasible; therefore surgery should aim to restore cerebrospinal fluid circulation, release engulfed neurovascular structures, and relieve brainstem compression. Intra-axial epidermoids are extremely rare. We present an innovative surgical technique of a cyst-cisternal shunting to treat cystic recurrent, unresectable brainstem epidermoids. METHODS: The surgical technique is stepwise described and a case illustration is reported. The pertinent literature has been reviewed. RESULTS: Few cases of brain stem epidermoid tumors have been described to date. The surgical steps of this technique and related intraoperative images are provided. One case illustration regarding the resection of a large recurrent cystic intra-axial brainstem epidermoid is reported to demonstrate the application of the technique in a clinical setting. The patient was followed up for 14 years and did not experience any recurrence, showing a stable disease at the last follow-up control. A systematic review of the competent literature has been provided. CONCLUSIONS: Cyst-cisternal shunting in case of recurrent, brainstem epidermoid is a safe and long-term effective technique to relieve mass effect into the brainstem.

Prosepective Study to Evaluate Rate and Frequency of Perturbations of Implanted Programmable Hakim Codman Valve After 1.5-Tesla Magnetic Resonance Imaging.

BACKGROUND: Exposure to magnetic fields may alter the settings of programmable ventriculoperitoneal shunt valves or even cause permanent damages to these devices. There is little information about this topic, none on live patients. OBJECTIVE: To investigate the effects of 1.5-tesla magnetic resonance imaging (MRI) on Hakim-Codman (HC) pressure programmable valves implanted in our hospital. METHODS: A single-center prospective study to assess the rate of perturbations of HC programmable valve implanted. One hundred consecutive patients implanted for different clinical reasons between 2008 and 2012 were examined. A conventional skull x-ray before and after a standard MRI on 1.5 tesla. We evaluated before and after results, analyzed modification rate, and verified eventual damages to the implanted devices. RESULTS: Implanted HC valves are extremely handy and durable, even if they are likely to change often due to the exposure to magnetic fields. None of the patients complained of heating effects. Oscillations range from 10-30 mm H2O with a patient who reached 50 mm H2O and 1 who reached 60 mm H2O. Global alteration rate was 40%: 10 patients (10%) experienced a 10 mm H2O change; 14 patients (14%) had a 20 mm H2O change; 6 patients (6%) had a 30 mm H2O change; 8 patients (8%) had a 40 mm H2O change; 1 patient had a 50 mm H2O change; and 1 patient had a 60 mm H2O change. CONCLUSIONS: HC valves presented a variable perturbation rate, with an alteration rate of 40% with 1.5-telsa MRI. We have not observed malfunctioning hardware as a result of magnetic influence. We claim ​ a cranial x-ray immediately after the MRI because of a high risk (40%) of decalibration, especially in patients with low ventricles compliance.

Neurosurgical treatment of craniopharyngioma in adults and children: early and long-term results in a large case series.

OBJECT: Craniopharyngioma accounts for 2%-5% of all primary intracranial neoplasms. The optimal management of craniopharyngioma remains controversial. The authors evaluated the early results of surgery and the longterm risk of tumor recurrence in a large series of patients undergoing resection of craniopharyngiomas. METHODS: Between 1990 and 2008, 112 consecutive patients (57 male and 55 female patients with a mean [± SEM] age of 33.3 ± 1.8 years) underwent resection of craniopharyngiomas at the authors' hospital. Recurrence or growth of residual tumor tissue during follow-up was assessed using MR imaging. RESULTS: There were 3 perioperative deaths (2.7%). Severe adverse events were more frequent in patients who underwent operations via the transcranial route (37%) than the transsphenoidal approach (5.6%; p < 0.001). Magnetic resonance imaging showed radical resection of the tumor in 78 (71.6%) of the remaining 109 patients. Previous surgery and maximum tumor diameter were associated with persistence of disease after surgery. Craniopharyngioma recurred in 26 (24.5%) of 106 patients. Presence of residual tumor on the first postoperative MR imaging, male sex, and no postoperative radiation therapy were associated with a risk of tumor recurrence. Quality-of-life data were assessed in the 91 patients who attended the authors' institution for follow-up visits. Among them, 8.8% patients were partially or completely dependent on others for daily living activities before surgery. This percentage increased to 14.3% at the last follow-up visit. The 5- and 10-year overall survival rates were 94.4% (95% CI 90.0%-98.8%) and 90.3% (95% CI 83.4%-97.3%), respectively. CONCLUSIONS: Complete surgical removal of craniopharyngioma can be achieved with reasonable safety in more than 70% of patients. Recurrence of craniopharyngioma may occur even after apparent radical excision. Prompt management of residual or recurring disease by radiotherapy, repeat surgery, or a combination of both is usually successful in controlling further tumor growth.

A case of melanotic desmoplastic ganglioglioma.

We describe a case of desmoplastic infantile ganglioglioma (DIG) in a 9-month-old boy located in the temporal lobe. Grossly the tumor was brown and superficially located. Histologically the tumor contained pigment in numerous neoplastic cells, shown to be melanosomal melanin by ultrastructural examination. Pigmented neoplasms have been reported at various sites in the central and peripheral nervous system. Previous reports on pigmented neuroepithelial tumors include neoplasms containing melanin, while others have contained neuromelanin and or lipofuscin. This case represents the first description of pigmented neoplastic cells in DIG, enlarging the spectrum of pigmented primary CNS tumors.

No salvage using high-dose chemotherapy plus/minus reirradiation for relapsing previously irradiated medulloblastoma.

PURPOSE: Myeloablative regimens were frequently used for medulloblastoma relapsing after craniospinal irradiation (CSI): in 1997-2002, we used repeated surgery, standard-dose and myeloablative chemotherapy, and reirradiation. METHODS AND MATERIALS: In 10 patients, reinduction included sequential high-dose etoposide, high-dose cyclophosphamide/vincristine, and high-dose carboplatin/vincristine, then two myeloablative courses with high-dose thiotepa (+/- carboplatin); 6 other patients received two of four courses of cisplatin/etoposide. Hematopoietic precursor mobilization followed high-dose etoposide or high-dose cyclophosphamide or cisplatin/etoposide therapy. After the overall chemotherapy program, reirradiation was prescribed when possible. RESULTS: Seventeen patients were treated: previous treatment included CSI of 19.5-36 Gy with posterior fossa/tumor boost and chemotherapy in 16 patients. Fifteen patients were in their first and 2 in their second and third relapses, respectively. First progression-free survival had lasted a median of 26 months. Relapse sites included leptomeninges in 9 patients, spine in 4 patients, posterior fossa in 3 patients, and brain in 1 patient. Three patients underwent complete resection of recurrence, and 10 underwent reirradiation. Twelve of 14 patients with assessable tumor had an objective response after reinduction; 2 experienced progression and were not given the myeloablative courses. Remission lasted a median of 16 months. Additional relapses appeared in 13 patients continuing the treatment. Fifteen patients died of progression and 1 died of pneumonia 13 months after relapse. The only survivor at 93 months had a single spinal metastasis that was excised and irradiated. Survival for the series as a whole was 11-93 months, with a median of 41 months. CONCLUSIONS: Despite responses being obtained and ample use of surgery and reirradiation, second-line therapy with myeloablative schedules was not curative, barring a few exceptions. A salvage therapy for medulloblastoma after CSI still needs to be sought.