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Background:  Lesions within the primary motor cortex (M1) and the corticospinal tract (CST) represent a significant surgical challenge with a delicate functional trade-off that should be integrated in the overall patient-centered treatment plan., Methods:  Patients with lesions within the M1 and CST with preoperative cortical and subcortical mapping (navigated transcranial magnetic stimulation [nTMS] and tractography), intraoperative mapping, and intraoperative provisional histologic information (smear with and without 5-aminolevulinic acid [5-ALA]) were included. This independently acquired information was integrated in a decision-making process model to determine the intraoperative extent of resection., Results:  A total of 10 patients (6 patients with metastatic precentral tumor; 1 patient with grade III and 2 patients with grade IV gliomas; 1 patient with precentral cavernoma) were included in the study. Most of the patients (60%) had a preoperative motor deficit. The nTMS documented M1 invasion in all cases, and in eight patients, the lesions were embedded within the CST. Overall, 70% of patients underwent gross total resection; 20% of patients underwent near-total resection of the lesions. In only one patient was no surgical resection possible after both preoperative and intraoperative mapping. Overall, 70% of patients remained stable postoperatively, and previous motor weakness improved in 20%., Conclusion:  The independently acquired anatomical (anatomical MRI) and functional (nTMS and tractography) tests in patients with CST lesions provide a useful guide for resection. The inclusion of histologic information (smear with or without 5-ALA) further allows the surgical team to balance the potential functional risks within the global treatment plan. Therefore, the patient is kept at the center of the informed decision-making process., Competing Interests: None declared., (Thieme. All rights reserved.)

This study aimed at describing the first case of subcortical stimulation of the corticospinal tract leading to selective contraction of the intercostal muscles during surgery for removal of a tumour centred in the right central lobule/supplementary motor area. A 53-year-old male presented with partial motor seizures. Imaging demonstrated a low-grade glioma affecting the posterior aspect of the superior and middle frontal gyri and invading the precentral gyrus. Preoperative motor Transcranial Magnetic Stimulation and advanced diffusion tractography were performed to establish the relationship of the tumour with the motor cortex and corticospinal tract. Intraoperative motor mapping and monitoring were performed with monopolar stimulation ("train of 5" technique). At the posterior margin of resection, subcortical stimulation demonstrated a selective response from intercostal muscles, medial to responses from the lower limb and lateral to responses from the upper limb. PubMed literature search was performed to identify any case reporting similar findings. There were no cases previously reported in the literature. The location of the subcortical response for intercostal muscles confirms the somatotopy of the corticospinal tract. Intercostal muscles are controlled by selective fibres within the corticospinal tract. Damage to these fibres can lead to paralysis of voluntary respiratory muscles. Further studies are needed to define the cortico-subcortical network controlling voluntary respiratory muscles.

OBJECTIVEVenous thromboembolism (VTE) is a major cause of morbidity in patients undergoing neurosurgical intervention. The authors postulate that the introduction of a routine preoperative deep vein thrombosis (DVT) screening protocol for patients undergoing neurosurgical intervention for brain tumors would result in a more effective diagnosis of DVT in this high-risk subgroup, and subsequent appropriate management of the condition would reduce pulmonary embolism (PE) rates and improve patient outcomes.METHODSThe authors conducted a prospective study of 115 adult patients who were undergoing surgical intervention for a brain tumor. All patients underwent preoperative lower-limb Doppler ultrasonography scanning for DVT screening. Patients with confirmed DVT underwent a period of anticoagulation therapy, which was stopped prior to surgery. An inferior vena cava (IVC) filter was inserted to cover the perioperative period during which anticoagulation therapy was avoided due to bleeding risk before restarting the therapy at a later date. Patients underwent follow-up performed by a neurooncology multidisciplinary team, and subsequent complications and outcomes were recorded.RESULTSSeven (6%) of the 115 screened patients had DVT. Of these patients, one developed postoperative PE, and another had bilateral DVT postoperatively. None of the patients without preoperative DVT developed VTE postoperatively. Age, symptoms of DVT, and previous history of VTE were significantly higher in the group with preoperative DVT. There were no deaths and no complications from the anticoagulation or IVC filter insertion.CONCLUSIONSPreoperative screening for DVT is a worthwhile endeavor in patients undergoing neurosurgical intervention. A multidisciplinary approach in management of anticoagulation and IVC filter insertion is safe and can minimize further VTE in such patients.

Despite review papers claim for radical treatment of oligometastatic patients, only few surgical series have been published. In this study, we analyze results and actual role of surgical resection for the management of patients with multiple brain metastases. This retrospective study compares surgical results of two groups of patients consecutively treated in our Institute from January 2004 to June 2015. The first group comprises all 32 patients with multiple brain metastases with only 2-3 lesions who underwent surgical resection of all lesions; the second group comprises 30 patients with a single surgically treated brain mestastasis compatible with the first group (match-paired control series). Median survival was 14.6 months for patients with multiple brain metastases (range 1-28 months) and 17.4 months for patients with a single brain metastasis (range 4-38 months); the difference was not statistically significant (P = 0.2). Neurological condition improved in 59.4% of patients with multiple metastases, it remained unchanged in 37.5% and worsened in 3.1%. In our series, selected patients with only 2-3 lesions with well-controlled systemic disease, life expectancy of more than 3 months, Karnofsky's performance status > 60, and surgically accessible lesions, benefited from surgical treatment in terms of survival and quality of life, with reduction or disappearance of significant neurological deficits. The prognosis for these patients is similar to that of patients with a single metastasis. It seems that patients with breast cancer included in our series had the worst prognosis if compared to other histotypes.

Brain metastases (BMs) are the most common intracranial tumour in adults and form a significant proportion of the neuro-oncology workload. Their management has progressed significantly in the last few decades but a gold-standard evidence-based management strategy has not been defined to date and several guidelines based on available evidence exist to support clinical decision-making. This paper evaluates the decision-making process of the neuro-oncology multi-disciplinary team (MDT) in a tertiary neuro-oncology centre over a two-year period. A retrospective review of all patients with BM discussed in the MDT was conducted. Data on patient demographics, tumour characteristics and MDT decision were collected from the MDT database, clinical notes and imaging studies. Patients were stratified into the three recursive partitioning analysis (RPA) classes and according to the graded prognostic assessment (GPA) score. MDT decisions were analysed by RPA class and for GPA score as well as single versus multiple BM. There were 362 patients with BM, representing 22% of the total cases discussed at the MDT. Decision-making was largely consistent with available guidelines. A concrete treatment decision was reached in 77.5% of patients and 32.2% of these received neurosurgical input. More patients with solitary BM underwent surgery compared to multiple BM (p = 0.001), and more patients in RPA classes I and II had surgical resection compared to class III (p = 0.005 and 0.001, respectively). Surgical patients also had higher GPA scores compared to palliative patients (p = 0.005). A greater absolute number and proportion of patients in RPA class II vs. class I underwent neurosurgical intervention. These patients were stratified into class II because of their age but would otherwise have been placed into class I. Survival data were available for 195 patients (53.8%) at 1 year post MDT discussion. A pattern of declining survival was observed along RPA classes which was statistically significant (p = 0.0025). Median survival was 4.7 (0-41), 3.7 (0-23), and 2.5 (range 0-24) months for RPA class I, II and III respectively. A similar pattern that did not reach statistical significance was found between GPA scores (p = 0.101). Median survival was 3 (0-13), 4.6 (range 0-41), and 4.6 (0-35) months for GPA scores 0-1.0, 1.5-2.5 and 3-4.0, respectively. Patient selection was generally in accordance to RPA class and GPA scoring, with the exception of surgery offered to elderly patients: this can be explained by the increasing number of otherwise fit patients as population ages.

Papillary tumor of the pineal region (PTPR) is a rare variety of CNS neoplasms and, since its first definition in 2003, only 64 cases have been described. PTPR is a primary neoplasm morphologically characterized by papillary structure staining for cytokeratin, transthyretin, neurone-specific enolase and S-100 protein. We report on a case of about 4 years' clinical history and neuroradiological follow-up of PTPR, in a 47-year-old Indian patient, with the aim of increasing the knowledge of its natural history. We describe through CT and MRI scans the natural evolution of this neoplasm, enhancing changes and morphologic structures involved, together with the final surgical treatment and pathological details. A mean growth rate average was calculated for this kind of lesion. In conclusion, the inexorable progressive growing nature of this tumor leads us to advocate an aggressive attitude among neurosurgeons and radiotherapists, with a precocious surgical approach when the suspicion rises.

Unlabelled: Despite aggressive multimodality treatment the prognosis of patients with primary brain tumors (BT) remains poor. At present, there are no data about the role of palliative home-care services and their impact on quality of care. We report the results of a pilot project of palliative home care for BT patients started in 2000 in the National Cancer Institute Regina Elena of Rome. We report also the result of a cost/effectiveness analysis utilizing administrative data on re-hospitalization rate in the last two months of life., Methods: Since October 2000 until December 2009, 572 patients have been followed by our home care staff. Among 394 patients who died, 276 (70%) were followed at home until death. A cost/effectiveness analysis was carried out evaluating the rehospitalization rate in the last 2 months of life in a subgroup of patients (group 1 assisted at home, 72 patients; group 2 not assisted at home, 71). The number of hospital readmission in the last 2 months of life, and length and cost of hospitalization were retrospectively analyzed from hospital discharge records., Results: Hospitalization rate of group 1 (16.7%) was lower than group 2 (38%) (95% CI: 0.18-0.65, p = 0.001). Costs of hospitalization also differed substantially: 517 Euros (95% CI: 512-522) in group 1 vs 24, 076 Euros (95%: 24,040-24,112 Euros) in group 2., Conclusion: Home-care may represent an alternative to in-hospital care for the management of brain tumor patients and may improve the end-of-life quality of care.

Not all Glioblastoma multiforme (GBM, grade IV WHO) manifest the same clinical course. Different prognostic classes may arise from different morphologic and genetic profiles. The observation of oligodendroglial foci within GBM samples and their correlation with genetic alterations may predict a better prognosis. 450 patients affected by histologically proven supratentorial cerebral GBM were treated at our institutions from January 2000 to December 2006: all patients received at least subtotal surgical removal, followed by the same standard radio-chemotherapy adjuvant treatment. In a subgroup of 36 patients (8.0%) an oligodendroglial component was observed. Molecular assessment of these cases was performed and LOH for 1p, 19q and 10q, EGFR amplification and TP53 gene expression was determined. Median age of this subgroup was 52.1 years (range: 29-78 years) vs 62.4 years in the entire GBM population. Chromosome analysis resulted as follows: LOH 1p and/or 19q in 27 cases (75.0%), LOH of 10q in 21 cases (58.1%), EGFR amplification in 14 cases (39%) and TP53 mutation in eight patients (22.2%). OS was of 20.9 months while it was 13.6 months in the entire GBM population. Progression free survival (PFS) was 10.3 months and 7.6 months the entire group. Two-year survival was of 55%. The presence of an oligodendroglial component in GBM appears to be an important prognostic factor to which better prognosis can be related. LOH 1p and 19q was significantly associated with GBM with oligodendroglial component.

Astroblastoma is one of the rarest tumors of the central nervous system (CNS), and its classification, histogenesis, diagnosis and therapeutic management are still being debated. The typical histopathological appearance is the perivascular, astroblastic pseudorosette, which is however present in other CNS tumors. To clarify the clinical, radiological, histopathological, prognostic and therapeutic characteristics, which have been treated only recently and are not well established yet due to the rarity of this tumor, six cases of histologically proven astroblastoma were retrospectively analyzed in light of more pertinent literature and paying special attention to therapeutic remarks. Between 1996 and 2005, six patients with cerebral astroblastoma were surgically treated at the Department of Neurosciences-Neurosurgery of Sapienza University in Rome. In three cases the lesion was termed low-grade astroblastoma, and high grade in the other three, according to current standard parameters. Median age of the six patients was 36 years. The time to diagnosis ranged from 1 week to 18 months. The radiological and anatomopathological features of this lesion are described. Surgical removal was total in four cases and subtotal in two. All patients received radiotherapy: two also had chemotherapy with temozolomide (TMZ). The three patients with low-grade astroblastoma are still alive today after a follow-up of 2, 5 and 19 years, respectively. Of the three patients with high-grade lesions, one is still alive after a 7-year follow-up, while the other two survived for 17 months (progression time 15 months) and 35 months (progression-reoperation time 23 months), respectively. Conclusions radical surgical resection is the treatment of choice for astroblastomas. Radiotherapy may play an adjuvant role in the treatment of high-grade lesions. The role of chemotherapy is still very debatable. We propose an aggressive standardized treatment for those lesions that meet anaplastic criteria, owing to their postulated glial origin and the propensity to have aggressive courses, and we advocate the use of a safe adjuvant chemotherapeutic regimen with TMZ, used concomitantly and subsequently to radiotherapy, especially for the high-grade astroblastoma cases. Multicenter studies, taking into account molecular biological findings, are necessary to define a common therapeutic strategy for astroblastomas.

With the increasing number of cancer survivors, we can observe a population that will present a higher risk of developing secondary long-term toxicities related to adjuvant chemo and radiotherapy regimens. Among these, children surviving from acute lymphoblastic leukemia (ALL) that were treated with prophylactic cranial irradiation represent a group of patients at a high risk of developing secondary brain tumors. Radiation-induced intracranial tumors have been documented since 1950, and today, more than one-hundred cases have been described. We report our experience with two young patients who were hospitalized for low grade gliomas and had a positive anamnesis for ALL and consequent radiotherapy.

Background: We report a leiomyosarcoma of the uterus, an uncommon tumor with a very aggressive course and poor prognosis due to the fact that, despite complete resection, it recurs with micrometastases. The most common metastatic sites are the lung, intraperitoneal, pelvic and paraaortic lymph nodes, and liver. Brain and skull metastases are very rare., Case: A 57-year-old woman underwent a hysterectomy and bilateral salpingooophorectomy for a grade T2N0M0 uterine leiomyosarcoma. There was no evidence of other lesions. Three months later a total-body PET scan demonstrated the presence of metastases in both lungs, and the patient was started on chemotherapy. One year later a cranial MRI demonstrated a brain metastasis to the temporal lobe. Emergency complete resection of the recurrence was performed, followed by whole-brain radiation and adjuvant chemotherapy., Conclusions: Given the limited treatment options, the gold standard for uterine leiomyosarcoma brain metastasis is total surgical removal. Chemotherapy and radiation therapy may provide only palliative benefit.

The authors report their personal experience with a surgical series of 16 cases of cerebral radiation-induced gliomas, defining diagnostic criteria and surgical and clinical characteristics. There were ten males and six females, with a median age of 45.9 years. Irradiation had initially been given for acute lymphoblastic leukemia (ALL) in six cases, tinea capitis in four cases, scalp hemangioma in three cases, cutaneous hemangioma, cavernous angioma, and medulloblastoma in one case each. There were 14 cases of glioblastoma (grade IV WHO) and 2 cases of astrocytoma (grade II WHO), with a mean latency time of 17 years (range: 6-26 years). For glioblastomas mean survival time was 10.4 months, accounting for 1-3% of all the glioblastomas treated. A thorough revision of the pertinent literature revealed some clinical-biological peculiarities.

When treating patients harboring a brain tumor, it is mandatory to integrate the dogmas of epilepsy into a neuro-oncological viewpoint. The frequency of seizures differs widely between low- and high-grade tumors because of different mechanisms of epileptogenesis. The modern theories of pathological neural networks, especially in low-grade gliomas, can provide the key for an in-depth understanding of the principles of connectionism that underline both seizures, cognitive impairment and plasticity. It is a consuetude that principles of general management of patients with nontumor-related epilepsy are applied to neuro-oncology. Nevertheless, since tumors are complex evolving lesions requiring a multidisciplinary treatment approach (surgery, radiotherapy and chemotherapy), it is mandatory to have a comprehensive view of the natural history of each lesion when choosing the best antiepileptic drug. More than two thirds of patients with brain tumors and medically intractable epilepsy benefit from (sub)total surgical resection. Therefore, these patients are good surgical candidates both for oncological and epileptological considerations, in order to change the natural history of the lesion and to improve the quality of life at the same time. However, 15% of patients still have intractable medical seizures after surgery. Moreover, the insula may participate more often than usually considered in (intractable) seizures. Therefore, in these patients, invasive EEG recordings and eventually a second epilepsy surgery might be proposed.

Aims and Background: Late brain metastases from breast cancer are a rare event. Only a few cases have been reported in the English literature. The authors describe the clinical and pathological remarks, together with treatment modalities, removal extent and overall survival, of 11 patients in whom brain metastases were detected more than 10 years from the primary tumor., Patients and Methods: Between January 1997 and April 2001, we hospitalized 11 patients, all females, with a histologically proven diagnosis of brain metastasis from breast invasive ductal carcinoma. We defined 'late metastasis' as those metastases that appeared at least 10 years after the breast cancer diagnosis. The median age at the moment of brain metastasis diagnosis was 59 years (range, 47-70), with a median latency time from breast cancer diagnosis of 16 years (range, 11-30)., Results: Ten patients underwent surgery followed by adjuvant radiotherapy (whole brain radiotherapy). Two of them received, after whole brain radiotherapy, stereotaxic radio surgery treatment. One patient had stereotaxic brain biopsy, performed by neuronavigator, followed by palliative corticosteroid therapy. Median survival after brain metastasis diagnosis was 28 months (range, 3 months-4 years)., Conclusions: Although late brain metastases are a rare event, specific neurologic symptoms and neuroradiological evidence of a cerebral neoplasm should be correlated to the presence of a cerebral metastasis, in a patient with a previous history of breast cancer. The longer latency time from breast cancer to brain metastasis could be explained by the "clonal dominance" theory and by different genetic alterations of the metastatic cell, which could influence the clinical history of the disease.

Background: Gliosarcoma is a rare cerebral tumor that has only recently been classified as a separate clinico-pathological entity, even though it remains closely related to glioblastoma in terms of both its clinical and therapeutic characteristics. The onset of this tumor during childhood is particularly unusual., Discussion: The authors describe three cases of gliosarcoma in three patients of 13, 15, and 16 years old, in an attempt to identify any distinctive aspects of the "juvenile" variety. On the basis of their personal experience and in the light of the available literature, the authors review the salient features of this pathological condition in young patients to identify any distinctive aspects as well as to define the significance of the extent of the sarcomatous component and of a "meningioma-like" appearance of the lesion, in terms of survival., Conclusion: In particular, they emphasize how modern diagnostic-therapeutic protocols make it possible to achieve a massive cytoreduction of the lesion in absolute safety in many cases, while avoiding further deficits in others, thus ensuring not only significant survival times but also a good quality of life.

Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival.

Brain metastasis from prostate carcinoma occurs very rarely. We describe 13 patients with single brain metastasis from prostatic cancer. Total removal of the lesions was performed in ten patients. Three patients underwent stereotactic biopsy. All patients were treated with postoperative whole brain radiotherapy (WBRT). Eight patients died for systemic disease after a mean time of 9.2 months with a diagnosis of metastasis. Five patients are still alive at 20, 14, 11, 7 and 6 months, respectively. Even if brain metastasis from prostate cancer is often a terminal event with death occurring within few months from diagnosis, we suggest the same protocol (surgery and/or radiosurgery plus postoperative WBRT) usually adopted to treat brain metastasis from other primitive tumours. A non specific neurological symptomatology and a possible normal dosage of serum specific antigen may contribute to a delay in diagnosis. However, considering the rarity of brain metastasis from prostate carcinoma, standard brain MRI follow-up in men with prostatic cancer does not seem to be necessary yet.

The association between breast cancer and glioblastoma multiforme has not been amply analyzed in the literature. We describe 11 female patients with a diagnosis of glioblastoma multiforme who were treated when younger for breast cancer. We believe that this association is not due to chance but rather to genetic changes in hormone status and in particular to sex hormones. Another important point of view is represented by the chemotherapy treatment of breast cancer, which could have a carcinogenic effect and explain the growth of glioblastoma. This consideration, in our opinion, is important, because more effort should be made to understand the pathogenesis of glioblastoma multiforme and to improve the therapeutic approaches.

The association between multiple sclerosis and tumours of the central nervous system is unusual. The authors analyzed the clinico-pathological elements of the correlation. The pertinent literature on this subject is critically reviewed. Ten cases of patients with an history of multiple sclerosis for more than 15 years and a clinical and radiological evidence of brain tumour were submitted to surgery in order to remove the lesion and/or to chemo- and radiotherapy. The various aspects of the association were studied in detail. A patient with multiple sclerosis, particularly with atypical symptoms, should be evaluated by an annual MRI investigation with intravenous paramagnetic contrast medium. The diagnostic work-up should be: clinical and radiological assessment; MRI in the event of atypical symptoms; Sstereotactic or neuronavigation-aided biopsy in any suspected lesions. Patients with multiple sclerosis and glioma present survival times identical to those observed in patients not suffering from multiple sclerosis. The coexistence of multiple sclerosis and brain tumours does not seem to influence the clinical evolution of either of these pathologies. We believe that it is important to achieve an early diagnosis of brain tumour in such patients with a clinical and neuroradiological follow up, so that they can be treated promptly.

Aims and Background: To add a further contribution to the literature supporting the relationship between previous head trauma and development of glioma., Methods: We report on four patients who developed brain gliomas in the scar of an old brain injury., Results: All cases fulfilled the widely established criteria for brain tumors of traumatic origin. In all of our cases there was radiological evidence of absence of tumor at the time of the injury., Conclusions: We believe that in specific cases it is reasonable to acknowledge an etiological association between a severe head trauma and the development of a glioma. This assumption is further sustained if there is radiological and surgical documentation of the absence of neoplasia at the moment of the trauma.

Brain metastases from renal carcinoma may appear even a long time after surgical treatment of the primary tumor. The authors present 2 series of patients, one of which has already been published and the other new, for a total of 4 cases of brain metastasis from renal carcinoma with late onset, which occurred 13, 17, 26 and 12 years after primary surgical treatment. The other cases described in the literature were also critically reviewed.

The aim of this study was to evaluate the efficacy of multimodality treatment of glioblastoma multiforme in the elderly. Although several studies report a poor outcome in elderly patients with glioblastoma, in the light of our experience, treatment of elderly patients with glioblastoma in non-critical areas and Karnofsky Performance Status > 60 should be just as aggressive as in younger patients.