Endovascular Treatment of Ruptured Intracranial Blister Aneurysms: A Systematic Review and Meta-analysis.

BACKGROUND: Endovascular treatment of blister aneurysms is a promising approach, even though they are vascular lesions challenging to treat due to their angioarchitectural characteristics. PURPOSE: Our aim was to investigate clinical and radiologic outcomes after endovascular treatment of ruptured blister aneurysms. DATA SOURCES: PubMed, Ovid MEDLINE, Ovid EMBASE, Scopus, and the Web of Science were screened. STUDY SELECTION: We performed a comprehensive review of the literature from 2010 to 2019 reporting series of patients with blister aneurysms treated with an endovascular approach. DATA ANALYSIS: Event rates were pooled across studies using a random effects meta-analysis. DATA SYNTHESIS: A total of 32 studies reporting on 684 patients (707 aneurysms) were included. Stent placement, stent-assisted coiling, and flow diversion were the most commonly described treatments (282, 256, and 155 patients, respectively). The long-term complete occlusion rate was 76.9% (95% CI, 69.2%-83.9%). The perioperative complication rate was 8.9%, and clinical outcome at final follow-up was mRS <2 in 76.6% (95% CI, 68.2%-84.2%) of patients. The mortality rate was 4.7% (95% CI, 2.30%-7.80%). Among the different techniques, stent-assisted coiling is the one that had the higher rate of immediate occlusion (63.4%); however, the occlusion rate at the final follow-up was comparable among the different techniques. LIMITATIONS: Different techniques were described and data were reported in a nonhomogeneous way, possibly representing a bias in the present study. CONCLUSIONS: This study suggests that endovascular treatment of blister aneurysms is associated with good long-term occlusion rates and reasonable complication and mortality rates. There is no consensus on the best endovascular techniques in blister aneurysm management.

Site and type of craniopharyngiomas impact differently on 24-hour circadian rhythms and surgical outcome. A neurophysiological evaluation.

This study aimed to quantify 24h body core temperature (BcT°) and sleep-wake cycle rhythm alterations in craniopharyngioma (CP) patients and to identify markers related to the postsurgical outcomes. Ten consecutive CP patients underwent neuroradiological, endocrinological and ophthalmological evaluations, 24h BcT° and sleep-wake cycle recordings before and after endoscopic endonasal surgery. The sample included four women and six men. Nocturnal sleep efficiency was pathologically reduced in eight patients before surgery. Seven out of ten patients presented one to three daytime naps. 24h BcT° rhythm was pathological in six out of ten cases. Post-surgery sleep efficiency normalized in four out of eight patients, whereas nine out of ten patients presented with two to six longer daytime naps. Diurnal naps were mainly present in patients showing pre-operative involvement of the third ventricle floor. 24h BcT° remained pathological in only one out of six cases, returned to normal in two and improved in three. 24h BcT° rhythm improved more in papillary CPs than in adamantomatous CPs. Our data confirmed that both CP and surgery frequently disrupt the sleep-wake cycle and BcT° rhythms. Tumour location and histotype may be related to a worse postsurgical outcome. Therefore, in-depth investigation including circadian monitoring is crucial for surgical outcome.

Adjuvant chemotherapy in adult medulloblastoma: is it an option for average-risk patients?

The standard treatment in children with average-risk medulloblastoma (MB) is reduced-dose radiotherapy (RT) followed by chemotherapy. However, in adults, there is no agreement on the use of adjuvant chemotherapy. We performed a retrospective analysis of adult MB patients with average-risk disease, defined as no postsurgical residual (or ≤1.5 cm(2)) and no metastatic disease (M0). Main inclusion criteria were: age >16 years, post-surgical treatment with craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). From 1988 to 2012 were accrued 43 average-risk MB patients treated with surgery and adjuvant RT. Fifteen (34.9 %) patients received also chemotherapy: 7 before RT, 5 after RT, and 3 before and after RT. Reasons to administer chemotherapy were presence of residual disease (even if ≤1.5 cm) and delay in RT. After a median follow up time of 10 years (range: 8-13), median survival was 18 years (95 % CI 9-28) in patients who receive RT alone, and was not reached in patients treated with RT plus chemotherapy. The survival rates at 5, 10 and 15 years were 100 %, 78.6 % (95 % CI 60.0-97.2 %) and 60.2 % (95 % CI 36.9-83.5 %), in patients treated with RT alone, and 100, 100 and 100 %, in patients treated with RT plus chemotherapy (p = 0.079). Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult patients. Further improvements might drive to add chemotherapy in average-risk setting with less favourable biological signatures (i.e., non-WNT group).

Pathological spectrum in recurrences of glioblastoma multiforme.

INTRODUCTION: Glioblastoma (GBM) is the most frequent primary malignant brain tumour. Despite advances in treatment its prognosis remains poor. Histological features of GBM are well known. On the contrary histological description of recurrences is still not available. The aim of this study was to describe the morphological, immunohistochemical and molecular features of recurrent GBMs. METHODS: 25 recurrent GBMs, diagnosed after 2005, were collected. All patients had undergone an adjuvant treatment regimen (temozolomide and/or radiotherapy). All cases were immunostained using anti-GFAP, Olig2 and Nogo-A antisera. MGMT and IDH1 status was reassessed. Features of the recurrences were compared with those of primary GBMs, time of recurrence and survival. RESULTS: Recurrences were divided morphologically into three groups: 1) recurrences displaying the same features of primary GBM, were highly cellular, had the fastest progression and the worst prognosis; 2) recurrences changing dramatically morphological appearance, had a slightly longer survival, 3) poorly cellular recurrences, with sparse neoplastic cells intermingled with reactive and necrotic tissue, displayed the slowest progression and longer survival. MGMT and IDH1 status remained unchanged between primary tumours and recurrences. DISCUSSION: GBM histological subtypes display different reactions to adjuvant treatments, offering a possible role in predicting different recurrence and survival time.

Endovascular treatment of distal anterior cerebral artery aneurysms: single-center experience and a systematic review.

In this study, a single center's experience of 20 patients and a systematic review and a meta-analysis of 16 studies, including 279 patients/aneurysms, assessed the safety and efficacy of endovascular treatment of distal anterior cerebral artery aneurysms. The authors conclude that endovascular treatment of distal anterior cerebral artery aneurysms is associated with high angiographic occlusion rates, but the complication rates are higher compared with other aneurysms in the circle of Willis.

Angioarchitectural features of brain arteriovenous malformations associated with seizures: a single center retrospective series.

BACKGROUND AND PURPOSE: Epileptic seizures account for 24-40% of all clinical onsets in patients with brain arteriovenous malformations (AVMs). METHODS: We retrospectively reviewed the angioarchitectural features of AVMs associated with seizures in 168 patients admitted to our Department from 1997 to 2012. Patients were dichotomized according to demographic characteristics, type of treatment, bleeding occurrence, and morphological and topographic features. Clinical status at admission and discharge was also recorded. The association of each one of these variables with seizures occurrence was statistically tested. Continuous variables and outcome were compared with Student's t-test, whereas categorical ones were compared using Fisher's exact test. The independent contribution of some seizures predictors was assessed with a logistic regression model. Associations were considered significant for P < 0.05. RESULTS: About 29% patients showed seizures and 47% bleeding. No significant difference in age and sex was observed between patients with and without seizures. AVMs > 4 cm (P = 0.001) and those fed by dilated arterial feeders (P = 0.02) were associated with increased risk of seizures. A higher risk of seizures occurrence was also observed in cortical AVMs compared with deeper ones (75.5% vs. 55.4%; P = 0.01), and in AVMs fed by middle and posterior cerebral arteries branches compared with the other vessels (81.6% vs. 45.3%; P < 0.001 and 48.9% vs. 23.5%; P = 0.002, respectively). No lobar predisposition was observed. A nidus > 4 cm also appeared as an independent risk factor of seizures occurrence (OR 2.82; 95% CI, 1.26-6.31; P = 0.009) at logistic regression analysis. CONCLUSIONS: AVM morphology, especially nidus dimension, appeared to more significantly influence seizures occurrence than their topography.

Results by motor cortex stimulation in treatment of focal dystonia, Parkinson's disease and post-ictal spasticity. The experience of the Italian Study Group of the Italian Neurosurgical Society.

Extradural motor cortex stimulation has been employed in cases of Parkinson's disease (PD), fixed dystonia (FD) and spastic hemiparesis (SH) following cerebral stroke. Symptoms of PD are improved by EMCS: results were evaluated on the basis of the UPDRS and statistically analysed. In PD EMCS is less efficacious than bilateral subthalamic nucleus (STN) stimulation, but it may be safely employed in patients not eligible for deep brain stimulation (DBS). The most rewarding effect is the improvement, in severely affected patients, of posture and gait. FD, unresponsive to bilateral pallidal stimulation, has been relieved by EDMS. In SH reduction of spasticiy by EMCS allows improvement of the motor function.

[Pediatric craniopharyngioma: long-term results in 61 cases]. / Craniofaringioma pediatrico: risultati a lungo termine in 61 casi.

AIM: The aim of this study was to analyze the long-term results of the surgical management of craniopharyngioma in children by reviewing a series of patients consecutively treated in a single institution, and to assess the efficacy of intratumoral chemotherapy with interferon-alpha. METHODS: Sixty-one paediatric patients (38 males and 23 females; mean age: 8 years) have been surgically treated in the last 20 years. The goal of surgery was to remove the tumour as much as possible. Postoperative radiotherapy was administered only to children aged more than 4 year old and with postsurgical evolutive remnant. Three patients were treated with intratumoral administration of interferon-alpha. The mean follow-up is 8.4 years (median: 7 years). RESULTS: All the 55 surviving patients enjoy a normal social life, except for 3 of them (visual and/or neurological deficits); endocrine function, compromised in 3/5 of cases, is managed by chronic hormone replacement; neuropsychological assessment is satisfactory in almost all the cases. Although obesity does not seem to be an important social limit, it represents a real management problem. Interferon-a was useful in transitorily arresting the growing cystic craniopharyngiomas. CONCLUSION: The current experience confirms the still remarkable challenges in the treatment of craniopharyngioma in childhood. Surgery should aim not only at removing the tumour, but also at preserving the late neuro-endocrinological functions. Intracystic chemotherapy with interferon-alpha might represent an effective option to postpone the surgical operation until the maturation of the hypothalamic-hypophyseal pathway is completed. However, it can not replace the traditional surgical management.

Extradural motor cortex stimulation (EMCS) for Parkinson's disease. History and first results by the study group of the Italian neurosurgical society.

The preliminary results obtained by the Study Group for Treatment of Involuntary Movements by Extradural Motor Cortex Stimulation (EMCS) of the Italian Neurosurgical Society, are reported. The series includes 16 cases of very advanced Parkinson's Disease (PD), aged 46-81; 15 of them were not eligible for Deep Brain Stimulation. Ten cases have been evaluated at 3-30 months after implantation. Unilateral, sub-threshold extradural motor cortex stimulation (2 8 Volt, 100-400 microsec., 20-120 Hz) by chronically implanted electrodes, relieves, at least partially, but sometime dramatically, the whole spectrum of symptoms of advanced PD. Tremor and rigor bilaterally in all limbs and akinesia are reduced. Standing, gait, motor performance, speech and swallowing are improved. Benefit is marked as far as axial symptoms is concerned. Also the symptoms of Long Term Dopa Syndrome -dyskinesias, motor fluctuations - and other secondary effect of levodopa administration psychiatric symptoms - are improved. Levodopa dosage may be reduced by 50%. The effect seems persistent and does not fade away with time. Improvement ranged, on the basis of the UPDRS scale, from <25% to 75%. There was only one case of complete failure. Quality of life is markedly improved in patients who were absolutely incapable of walking and unable arise out of chair. After stimulation they could walk, even if assistance was necessary. Improvement was observed also in those with disabling motor fluctuation and dyskinesias which could be abolished.

Combined treatment of glioblastoma patients with locoregional pre-targeted 90Y-biotin radioimmunotherapy and temozolomide.

AIM: In a previous phase I-II study, the safety profile and anti-tumor efficacy of pre-targeting locoregional radioimmunotherapy (LR-RIT), based on the ''3 step'' method, was assessed in 24 high-grade glioma patients. The encouraging results in terms of low toxicity and objective response rate (25%) prompted us to continue our study. METHODS: An analysis of 73 patients with hystologically confirmed glioblastoma multiforme (GBM), treated with the ''3 step'' (90)Y-biotin based LR-RIT, is herein reported. All patients had a catheter implanted at 2(nd) surgery and underwent at least 2 cycles of LR-RIT (range 2-7) with 2 months interval. Thirty-five out of 73 patients were also treated with Temozolomide (TMZ). Two cycles of TMZ (200 mg/m(2)/day, for 5/28 days) were administered in between each course of LR-RIT. Overall survival (OS) and progression free survival (PFS) were retrospectively calculated. RESULTS: Stabilization of disease was achieved in 75% of patients, while 25% progressed. In the 38 patients treated with LR-RIT alone, median OS and PFS were respectively 17.5 months (95%CI=[17-20]) and 5 months (95%CI=[4-8]), while in the 35 treated with the combined treatment (LR-RIT+TMZ) respective values were 25 months (95%CI=[23-30]) and 10 months (95%CI=[9-18] (p<0.01). The addition of TMZ to LR-RIT did not increase neurological toxicity, and no major hematological toxicity was observed. CONCLUSION: These results confirm the safety and the efficacy of (90)Y LR-RIT in recurrent GBM patients; the addition of TMZ significantly improved the overall outcomes; a further controlled prospective, randomized study is fully justified.

Spondylectomy (thoracolumbar spine) combined with dural resection for bone tumor: surgical technique.

The authors describe the technique of vertebral resection combined with resection and reconstruction of the dura mater for bone tumor. The literature relevant to this topic is reviewed.

Pre-targeted locoregional radioimmunotherapy with 90Y-biotin in glioma patients: phase I study and preliminary therapeutic results.

The aim of this study was to determine the maximum-tolerated dose, of a pre-targeting three-step (3-S) method employing 90Y-biotin in the locoregional radioimmunotherapy (RIT) of recurrent high grade glioma, and to investigate the antitumor efficacy of this new treatment. Twenty-four patients with recurrent glioma underwent second surgical debulking and implantation of a catheter into the surgical resection cavity (SRC), in order to introduce the radioimmunotherapeutic agents [biotinylated monoclonal antibody (MoAb), avidin and 90Y-biotin]. Eight patients with anaplastic astrocytoma (AA) and 16 patients with glioblastoma (GBM) were injected with biotinylated anti-tenascin MoAb (2 mg), then with avidin (10 mg; 24 h later) and finally 90Y-biotin (18 h later). Each patient received two of these treatments 8-10 weeks apart. The injected activity ranged from 0.555 to 1.110 GBq (15-30 mCi). Dosage was escalated by 0.185 GBq (5 mCi) in four consecutive groups. The treatment was well tolerated without acute side effects up to 0.740 GBq (20 mCi). The maximum tolerated activity was 1.110 GBq (30 mCi) limited by neurological toxicity. None of the patients developed hematologic toxicity. In three patients infection occurred around the catheter. The average absorbed dose to the normal brain was minimal compared with that received at the SRC interface. At first control (after 2 months), partial (PR) and minor (MR) responses were observed in three GBM (1 PR; 2 MR) and three AA patients (1 PR; 2 MR) with an overall objective response rate of 25%. Stable disease (SD) was achieved in seven GBM and five AA patients (50%). There was disease progression in six GBM patients (25%), but in none of the AA patients. At the dosage of 0.7-0.9 GBq per cycle, locoregional 3-S-RIT was safe and produced an objective response in 25% of patients. Based on these encouraging results, phase II studies employing 3-S-RIT soon after first debulking are justified.

Local treatment of malignant gliomas by direct infusion of specific monoclonal antibodies labeled with 131I: comparison of the results obtained in recurrent and newly diagnosed tumors.

Two murine monoclonal antibodies, BC-2 and BC-4, raised against tenascin and labeled with 131I were infused locally in the site of neoplastic disease by means of a removable (16 patients) or indwelling (34 patients) catheter. Fifty patients bearing a malignant glioma were treated. Twenty-six of these were suffering from recurrent disease; their tumors relapsed within 9 months (median) after treatment. The remaining 24 cases had a newly diagnosed tumor, and local radioimmunotherapy (RIT) was given immediately after surgery and radiochemotherapy. All efforts were made to reduce the tumor before the infusion of the radiopharmaceutical. Therefore, 22 cases with relapsing glioma underwent additional debulking surgery, which led to total or subtotal removal of tumor in 9 of the patients. Altogether, 28 patients had intralesional RIT when the disease was minimal or microscopic. Conversely, 22 cases underwent local RIT with a tumor the diameter of which was > 2 cm. In many cases, the infusions were repeated up to six times to achieve complete destruction of the neoplastic tissue. The local treatment did not give rise to systemic or to cerebral adverse effects. The labeled monoclonal antibodies, given directly in the site of the lesion, concentrated in very high amount in the neoplastic tissue and remained fixed in the target for a long period of time. For these reasons, the radiation dose to the tumor was remarkable (on average > 30,000 cGy/cycle) and consequently led to promising results. The median survival was, in total, 20 months (18 in recurrent tumors and 23 in newly diagnosed lesions). Moreover, median survival was 17 months in patients with bulky tumors (both recurrent and newly diagnosed tumors) and 26 months in patients with minimal or microscopic disease. The median time to progression was 3 months in recurrent and 7 months in newly diagnosed gliomas. Finally, RIT produced 3 CRs (all in recurrent tumors), 6 PRs (4 in recurrent and 2 in newly diagnosed), and 11 stabilizations of disease (4 in recurrent and 7 in newly diagnosed). In 19 cases (13 recurrent and 6 newly diagnosed) the progression of tumor was recorded. Eleven patients (2 recurrent and 9 newly diagnosed) who were treated by RIT when their disease was minimal and nondetectable by radiological methods remained disease-free and were classified as NED. The overall response rate (NED plus CR plus PR) was 40% (34.6% recurrent and 45.8% newly diagnosed).(ABSTRACT TRUNCATED AT 400 WORDS)

Intralesional administration of I-131 labelled monoclonal antibodies in the treatment of malignant gliomas.

The authors report their preliminary experience with the use of radiolabelled monoclonal antibodies (MAb) as an adjuvant treatment for 33 malignant gliomas. MAbs employed in this study are raised against Tenascin (TN) which is an antigen of the extracellular matrix of the tumour. It has also been found in neoplastic cells but never in normal brain tissue. This therapy is aimed to give a local high dose radiation (boost) while sparing healthy brain structures. This treatment has always been well tolerated and no adverse reactions at the level of CNS or major extraneural organs has been observed. Significant improvement of median survival has been obtained but this result should be cautiously evaluate since the study is non-randomized. Comparison with other current adjuvant technique is briefly discussed.

Intralesional radioimmunotherapy of malignant gliomas. An effective treatment in recurrent tumors.

BACKGROUND: Intralesional radioimmunotherapy (RAIT) may improve the management of malignant gliomas whose prognosis is, at present, very poor. Current treatment modalities (e.g., surgery, radiotherapy, and chemotherapy) may prolong survival by a few months but cannot prevent tumor recurrence. METHODS: Following one or more surgical operations, radiotherapy, and chemotherapy, 24 patients with recurrent malignant gliomas (23 brain and 1 spinal cord) underwent RAIT with 2 murine monoclonal antibodies (MoAb), BC-2 and BC-4, raised against tenascin (TN). This antigen is expressed in large amounts in the stroma of glial tumors but not normal brain tissue. The isotope used was iodine-131 (131I). The radiolabelled antibodies were injected directly into the tumor by means of a removable catheter or an indwelling catheter placed in the site of disease at the time of craniotomy. The patients were admitted to the protocol if histochemical analysis of their tumors demonstrated the presence of TN in high abundance. Biodistribution and dosimetry of an intralesional tracer dose (1 mg MoAb and 37 MBq 131I) were studied. RAIT was performed by the administration of escalating doses of radioiodine, ranging from 15 mCi to 57 mCi. In many cases, RAIT was was repeated two, three, or four times (on 8, 3 and 4 patients, respectively). RESULTS: Pharmacokinetic data resulted, on average, as follows: the 24-hour tumor/background ratio was 16.6; the percentage of injected dose concentrated per gram of tumor at 24 hours was 2.4%; and the effective half-life of the MoAb at the tumor was 74.5 hours. The mean radiation dose to the tumor was 36.48 cGy per MBq of 131I injected. Both systemic and brain toxicities were absent, while human anti-mouse antibody production after MoAb administration occurred in only a few cases. At present, 17 patients are assessable, with a median survival time of 16 months. Objective responses consisted of 5 tumor stabilizations (median time, 9 months), 3 partial remissions (11 months), and 3 complete remissions (15 months).

Glioblastoma therapy by direct intralesional administration of I-131 radioiodine labeled antitenascin antibodies.

Thirty patients with recurrent glioblastomas (29 brain, 1 spinal cord) received intralesional radioimmunotherapy aiming to control the progression of the tumor after surgery and radiotherapy. The BC-2 and/or BC-4 murine MAbs (Sorin-Biomedica, Saluggia, Italy) were utilized. They strongly react against tenascin (TN), which is an extracellular antigen expressed in large amounts by the stroma of glioblastoma but not by normal brain. The MAbs were labeled with I-131 and were injected directly into the tumor mass to maximize the antibody concentration in the tumor and to irradiate the neoplastic cells. The dose consisted, on average, of 3 mg antibody and 1100 MBq I-131. In most cases the radioimmunotherapy (RIT) applications were repeated two, three, or four times. No systemic adverse reactions were recorded. The brain tolerance to direct antibodies injection was quite good. The antibody concentration in the tumor was high and the MAb residence time in neoplastic tumor was prolonged. Consequently the mean radiation dose to the tumor was high: > 25,000 cGy/cycle. Of 23 evaluable patients, we recorded 7 tumor stabilization (lasting, on mean, 9.1 mo), 4 partial remission (10 mo), and 4 complete remission (18 mo). The overall response rate was 34.7%.

Radioimmunotherapy of gastrointestinal cancer and glioblastomas.

Two groups of patients with gastro-intestinal (GI) tumours (41) and recurrent glioblastoma (GBM), (17) underwent radioimmunotherapy after the failure of traditional treatments. A number of different MAbs were employed (anti-CEA and anti-Tenascin) which were labelled with I-131. The radiopharmaceuticals were administered by the intraperitoneal and intratumoral routes. As a rule the cycles were repeated to enhance the effectiveness of RIT. No significant early or late adverse effects were recorded. HAMA development was observed in all GI cases but only in a few GBM patients. The cumulative dose delivered to the target tumors was considerable (mean 8,900 cGy) in the GI group, and was much higher in the GBM patients (mean 51,700 cGy) owing to the particular modality of injection. Survival improved in both series of patients. The objective responses to RIT were promising: in the GI group 10 complete remissions (CR) and 6 partial remissions (PR) were observed, while in the GBM group 3 long-lasting CRs and 3 prolonged PRs were documented.