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Background: Angiocentric glioma (AG) is a rare, benign, and slow-growing tumor. First described in 2005, it is now gaining attention with respect to the possibility of being diagnosed. Even with no statistical differences between sex, it has been reported both in children and the elderly. A total of 120 cases have been described in the literature. The aim of this study is to provide new data for a new statistical assessment of the prevalence and incidence of AG in populations. Case report: An 8-year-old male patient with no history of epilepsy and no need for antiepileptic therapy underwent surgery for a left-parietal brain lesion, revealed through MRI. Imaging was acquired after his first absence episode. The lesion was completely resected. Histological findings indicated angiocentric glioma. No signs of recurrency after two years of follow-up. Conclusion: AG is usually an epilepsy-related low-grade glioma. Few cases exhibit disease progression and exitus. Surgical management should aim for a gross total resection to avoid recurrence and persisting epilepsy. Surgery represents the gold standard in diagnosis and treatment and must be performed as soon as possible in consideration of its healing properties and its useful diagnosis.

Arteriovenous malformation of the brain (bAVM) is a vascular phenotype related to brain defective angiogenesis. Involved vessels show impaired expression of vascular differentiation markers resulting in the arteriolar to venule direct shunt. In order to clarify aberrant gene expression occurring in bAVM, here we describe results obtained by methylome analysis performed on endothelial cells (ECs) isolated from bAVM specimens, compared to human cerebral microvascular ECs. Results were validated by quantitative methylation-specific PCR and quantitative realtime-PCR. Differential methylation events occur in genes already linked to bAVM onset, as RBPJ and KRAS. However, among differentially methylated genes, we identified EPHB1 and several other loci involved in EC adhesion as well as in EC/vascular smooth muscle cell (VSMC) crosstalk, suggesting that only endothelial dysfunction might not be sufficient to trigger the bAVM phenotype. Moreover, aberrant methylation pattern was reported for many lncRNA genes targeting transcription factors expressed during neurovascular development. Among these, the YBX1 that was recently shown to target the arteridin coding gene. Finally, in addition to the conventional CpG methylation, we further considered the role of impaired CHG methylation, mainly occurring in brain at embryo stage. We showed as differentially CHG methylated genes are clustered in pathways related to EC homeostasis, as well as to VSMC-EC crosstalk, suggesting as impairment of this interaction plays a prominent role in loss of vascular differentiation, in bAVM phenotype.

Among autophagic-related proteins, p62/SQSTM1/Sequestosome-1 represents a relevant actor in cellular proliferation and neoplastic growth. Although, recently, p62 expression has been analyzed in different neurodegenerative and glial neoplastic diseases, no available information have been reported in meningiomas, which have an high epidemiological relevance being the second most common category of intracranial tumors after gliomas. Generally meningiomas have a benign behavior, but their recurrence is not uncommon mainly when atypical or anaplastic varieties occur. However, intranuclear vacuoles have been ultrastructurally observed in meningiomas, and they were labelled by p62 antibodies. Therefore, in the present study, we have investigated p62 immunohistochemical pattern in a cohort of 133 cases representative of low- and high-grade meningiomas, to verify if p62 expression may be related to clinicopathological data, thus achieving a potential prognostic role. The p62 immunoexpression was frequently found in the nucleus and cytoplasm of neoplastic elements, and utilizing an intensity-distribution score, 55 (41.3%) cases were considered as high expressors while 78 (58.7%) cases were instead recorded as low expressors. Fifteen cases exhibited recurrences of the disease, 14 of which were codified as high expressors. Moreover, a direct relationship between p62 and Mib-1 immunoexpression as well as between p62 and neoplastic grade have been documented. Finally, we suggest that impaired autophagic flux with an increase in p62 expression may be involved in the activation of NRF2 also contributing in the development of recurrence in meningioma patients.

Introduction: Intraoperative Neurophysiological Monitoring (IOM) is widely used in neurosurgery but specific guidelines are lacking. Therefore, we can assume differences in IOM application between Neurosurgical centers. Research question: The section of Functional Neurosurgery of the Italian Society of Neurosurgery realized a survey aiming to obtain general data on the current practice of IOM in Italy. Materials and methods: A 22-item questionnaire was designed focusing on: volume procedures, indications, awake surgery, experience, organization and equipe. The questionnaire has been sent to Italian Neurosurgery centers. Results: A total of 54 centers completed the survey. The annual volume of surgeries range from 300 to 2000, and IOM is used in 10–20% of the procedures. In 46% of the cases is a neurologist or a neurophysiologist who performs IOM. For supra-tentorial pathology, almost all perform MEPs (94%) SSEPs (89%), direct cortical stimulation (85%). All centers perform IOM in spinal surgery and 95% in posterior fossa surgery. Among the 50% that perform peripheral nerve surgery, all use IOM. Awake surgery is performed by 70% of centers. The neurosurgeon is the only responsible for IOM in 35% of centers. In 83% of cases IOM implementation is adequate to the request. Discussion and conclusions: The Italian Neurosurgical centers perform IOM with high level of specialization, but differences exist in organization, techniques, and expertise. Our survey provides a snapshot of the state of the art in Italy and it could be a starting point to implement a consensus on the practice of IOM.

Introduction: Planning cranioplasty (CPL) in patients with suspected or proven post-traumatic hydrocephalus (PTH) poses a significant management challenge due to a lack of clear guidance. Research question: This project aims to create a European document to improve adherence and adapt to local protocols based on available resources and national health systems. Methods: After a thorough non-systematic review, a steering committee (SC) formed a European expert panel (EP) for a two-round questionnaire using the Delphi method. The questionnaire employed a 9-point Likert scale to assess the appropriateness of statements inherent to two sections: ''Diagnostic criteria for PTH'' and ''Surgical strategies for PTH and cranial reconstruction.'' Results: The panel reached a consensus on 29 statements. In the ''Diagnostic criteria for PTH'' section, five statements were deemed ''appropriate'' (consensus 74.2−90.3 %), two were labeled ''inappropriate,'' and seven were marked as ''uncertain.''In the ''Surgical strategies for PTH and cranial reconstruction'' section, four statements were considered ''appropriate'' (consensus 74.2−90.4 %), six were ''inappropriate,'' and five were ''uncertain.'' Discussion and conclusion: Planning a cranioplasty alongside hydrocephalus remains a significant challenge in neurosurgery. Our consensus conference suggests that, in patients with cranial decompression and suspected hydrocephalus, the most suitable diagnostic approach involves a combination of evolving clinical conditions and neuroradiological imaging. The recommended management sequence prioritizes cranial reconstruction, with the option of a ventriculoperitoneal shunt when needed, preferably with a programmable valve. We strongly recommend to adopt local protocols based on expert consensus, such as this, to guide patient care.

Skull primary intraosseous cavernous hemangiomas (PICHs) are uncommon, benign, and slowgrowing tumors. These lesions are not widely known, specifically as regards the pathogenesis. The researchers wanted to describe the clinical presentations and radiological characteristics through a literature review of 140 cranial patients who received surgical treatment and histological diagnosis. Although PICH is uncommon, it should always be considered when a hard, steadily expanding skull lesion is seen. Surgical resection should be the first line of therapy for symptomatic individuals and aesthetic motivation, and their long-term results following complete removal are excellent. Moreover, we describe four patients with PICH to enrich the literature.

Background: The COVID-19 pandemic and its impact on hospitals' activity and organization has imposed a vast change in standard neurosurgical oncology practice to accommodate for shifting resources. Aims: This investigation aims to analyse the nationwide capability in reorganizing the surgical neuro-oncological activity during the COVID-19 pandemic to evaluate whether COVID-19-pandemic influenced the surgical management in these patients. Method: A web-based dataset model organized by the Italian Neurosurgical Society (SINCh) was sent to all the Italian neurosurgical departments in May 2021, requesting to report the types and numbers of surgical procedures performed in the pre-pandemic period (from March 9th 2019 to March 9th 2020) compared to the pandemic period (from March 10th 2020 to March 10th 2021). Results: This multicentre investigation included the surgical activity of 35 Italian Neurosurgical Departments in a pre-pandemic year versus a pandemic year. During the COVID period, 699 fewer neuro-oncological patients were operated on than in the pre-COVID period. We noted a slight increase in urgency and a more severe decrease in elective and benign pathology. None of these differences was statistically significant. Surgically treated patients who tested positive for SARS-CoV-2 were 36, of which 11 died. Death was found to be COVID-related only in 2 cases. Conclusion: The reorganization of the Italian Neurosurgical Departments was able to guarantee a redistribution of the CNS tumors during the inter-pandemic periods, demonstrating that patients even in the pandemic era could be treated without compromising the efficacy and safety of the surgical procedure.

By regulating several phases of gene expression, RNA editing modifications contribute to maintaining physiological RNA expression levels. RNA editing dysregulation can affect RNA molecule half-life, coding/noncoding RNA interaction, alternative splicing, and circular RNA biogenesis. Impaired RNA editing has been observed in several pathological conditions, including cancer and Alzheimer’s disease. No data has been published yet on the editome profile of endothelial cells (ECs) isolated from human cerebral cavernous malformation (CCM) lesions. Here, we describe a landscape of editome modifications in sporadic CCM-derived ECs (CCM-ECs) by comparing editing events with those observed in human brain microvascular endothelial cells (HBMECs). With a whole transcriptome-based variant calling pipeline, we identified differential edited genes in CCM-ECs that were enriched in pathways related to angiogenesis, apoptosis and cell survival, inflammation and, in particular, to thrombin signalling mediated by protease-activated receptors and non-canonical Wnt signalling. These pathways, not yet associated to CCM development, could be a novel field for further investigations on CCM molecular mechanisms. Moreover, enrichment analysis of differentially edited miRNAs suggested additional small noncoding transcripts to consider for development of targeted therapies.

Eagle Syndrome (ES) is an often misdiagnosed syndrome due to its wide spectrum of signs and symptoms. Recent works have pointed out the relation between ES and some types of craniofacial pain often misdiagnosed with migraine or temporomandibular disorders. Moreover, the presence of Vascular ES as a cause of Carotid Artery Dissection in same cases of stroke as well as cause of intracranial venous hypertension resulting in migraine and other pains has been recently discussed. A multidisciplinary approach is mandatory to allow clinicians to better understand the pathophysiology and clinical main patterns of ES. The aim of the work is to perform a comprehensive review all the clinical patterns and available diagnostic tools to guide clinicians through lights and shadows of such an underestimated syndrome. Finally, a novel flow-chart for comprehensive diagnosis of ES is proposed, including “dynamic” imaging investigating the relationship between stiloyd processes and the neurovascular structures of the neck during head movements.

Background: Brain tumors can cause different changes in excitation and inhibition at the neuronal network level. These changes can be generated from mechanical and cellular alterations, often manifesting clinically as seizures.Objective/Hypothesis: The effects of brain tumors on cortical excitability (CE) have not yet been well-evaluated. The aim of the current study was to further investigate cortical–cortical and cortical–spinal excitability in patients with brain tumors using a more extensive transcranial magnetic stimulation protocol.Methods: We evaluated CE on 12 consecutive patients with lesions within or close to the precentral gyrus, as well as in the subcortical white matter motor pathways. We assessed resting and active motor threshold, short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), long-latency afferent inhibition, cortical silent period, and interhemispheric inhibition.Results: CE was reduced in patients with brain tumors than in healthy controls. In addition, SICI, ICF, and SAI were lower in the affected hemisphere compared to the unaffected and healthy controls.Conclusions: CE is abnormal in hemispheres affected by brain tumors. Further studies are needed to determine if CE is related with motor impairment.

IntroductionThe goal of brain tumor surgery is the maximal resection of neoplastic tissue, while preserving the adjacent functional brain tissues. The identification of functional networks involved in complex brain functions, including visuospatial abilities (VSAs), is usually difficult. We report our preliminary experience using a preoperative planning based on the combination of navigated transcranial magnetic stimulation (nTMS) and DTI tractography to provide the preoperative 3D reconstruction of the visuospatial (VS) cortico-subcortical network in patients with right parietal lobe tumors.Material and MethodsPatients affected by right parietal lobe tumors underwent mapping of both hemispheres using an nTMS-implemented version of the Hooper Visual Organization Test (HVOT) to identify cortical areas involved in the VS network. DTI tractography was used to compute the subcortical component of the network, consisting of the three branches of the superior longitudinal fasciculus (SLF). The 3D reconstruction of the VS network was used to plan and guide the safest surgical approach to resect the tumor and avoid damage to the network. We retrospectively analyzed the cortical distribution of nTMS-induced errors, and assessed the impact of the planning on surgery by analyzing the extent of tumor resection (EOR) and the occurrence of postoperative VSAs deficits in comparison with a matched historical control group of patients operated without using the nTMS-based preoperative reconstruction of the VS network.ResultsTwenty patients were enrolled in the study (Group A). The error rate (ER) induced by nTMS was higher in the right vs. the left hemisphere (p=0.02). In the right hemisphere, the ER was higher in the anterior supramarginal gyrus (aSMG) (1.7%), angular gyrus (1.4%) superior parietal lobule (SPL) (1.3%), and dorsal lateral occipital gyrus (dLoG) (1.2%). The reconstruction of the cortico-subcortical VS network was successfully used to plan and guide tumor resection. A gross total resection (GTR) was achieved in 85% of cases. After surgery no new VSAs deficits were observed and a slightly significant improvement of the HVOT score (p=0.02) was documented. The historical control group (Group B) included 20 patients matched for main clinical characteristics with patients in Group A, operated without the support of the nTMS-based planning. A GTR was achieved in 90% of cases, but the postoperative HVOT score resulted to be worsened as compared to the preoperative period (p=0.03). The comparison between groups showed a significantly improved postoperative HVOT score in Group A vs. Group B (p=0.03).ConclusionsThe nTMS-implemented HVOT is a feasible approach to map cortical areas involved in VSAs. It can be combined with DTI tractography, thus providing a reconstruction of the VS network that could guide neurosurgeons to preserve the VS network during tumor resection, thus reducing the occurrence of postoperative VSAs deficits as compared to standard asleep surgery.

Background: Stereotactic irradiation is proposed for treatment of pituitary adenomas (PAs) in patients with tumor progression/recurrence after surgery and in cases not eligible for other therapies. In the literature several papers have been published on the role of the Gamma-Knife stereotactic irradiation for management of PAs, but data on the role of stereotactic Cyberknife (CK) are still limited. We describe a single-center experience using CK stereotactic radiosurgery (CK-SRS) and hypofractionated radiotherapy (CK-SRT) for PAs treatment, analyzing its efficacy/safety in the light of current literature. Methods: We retrospectively collected clinical data from PAs patients treated using CK system at the University Hospital of Messina, Italy, between 2008 and 2018. The efficacy was evaluated by analyzing the tumor growth/biochemical disease control rates, and the safety by evaluating post-treatment pituitary and/or visual deficits. Results: Twenty-four PAs patients were included in the study. The mean follow-up was 42.21 ± 32.67 months. The overall tumor growth control rate was 91.6%, but it was higher using the single-session scheme (100%) than using hypofractionated sessions (80%). The biochemical disease control rate was 60%, but increased to 80% in GH-secreting PAs. Post-treatment hypopituitarism occurred in 41.66% of cases, being 35.71% using a hypofractionated scheme, and 50% using a single-session treatment. No cases of post-treatment visual deterioration were observed. Overall and progression-free survival were respectively 84.6% and 83.6% at three years. Conclusions: Cyberknife irradiation is an effective and safe option for PAs treatment, being associated to an excellent tumor growth/biochemical control of the disease, and to a low rate of post-treatment complications. The efficacy seems to be higher when using a single-session scheme even if this could be associated to a higher incidence of post-treatment hypopituitarism. Keywords: Cyberknife, Pituitary adenomas, Radiosurgery

Objective Angled scopes allow 360° visualization, which makes percutaneous endoscopic techniques (percutaneous endoscopic lumbar discectomy, PELD) particularly attractive for sequestrectomies, which entail the removal of extruded lumbar disc fragments that have migrated caudally or cranially between the ligaments, foramina, and neural structures, while preserving the disc. Although many different PELD techniques are currently available, not all of them are suitable for sequestrectomies; furthermore, long-term follow-up data are unfortunately lacking. Methods A pilot study was conducted on a cohort of 270 patients with lumbar radiculopathy undergoing minimally invasive spine surgery (PELD or microdiscectomy), of whom only 7 were eligible for endoscopic interlaminar sequestrectomy with disc preservation. The patients’ baseline conditions and clinical outcomes were measured with the Oswestry Disability Index and a visual analogue scale. Long-term follow-up was conducted using satisfaction questionnaires that were based on the MacNab criteria and administered by medical/nursing personnel not involved in their primary surgical management. Results EasyGo system was eventually used in 5 PELD cases. No dural tears, infections, or nerve root injuries were recorded in patients undergoing sequestrectomy. Surgical events, including blood loss and overall length of hospital stay, did not differ significantly among the 270 patients. In the group treated with endoscopic sequestrectomy, no recurrences or complications were noted during a follow-up of 3 years, and an excellent degree of satisfaction was reported. Conclusion We provide OCEBM (Oxford Centre for Evidence-Based Medicine) level 3 evidence that interlaminar endoscopic sequestrectomy is a tailored and well-tolerated surgical option; nonetheless, a cost-effectiveness analysis assessing the interval until return to working activities and long-term benefits is warranted.

Posterior cerebral artery (PCA) territory infarction involving occipital cortical damage can give rise to contralateral homonymous hemianopia. Here, we report two rare cases of patients with lesions in the left hemisphere PCA territory who developed right visuo-spatial neglect. One patient suffered right hemianopia and right visuo-spatial neglect after a stroke that damaged the left primary visual cortex and the callosal splenial fibers. The other unique case is of a patient who had a brain tumor in the posterior cerebral region in the left hemisphere and initially exhibited only right hemianopia that developed into right visuo-spatial neglect after tumor resection that included the splenial fibers. These cases indicate that, as in cases with damage in the right PCA territory, lesions in the left PCA yield visuo-spatial neglect when the damage produces contralateral hemianopia and concomitant disconnection of the splenium of the corpus callosum, which interferes with the arrival of visual inputs from the intact right to the lesioned left hemisphere. These results also emphasize the necessity of sparing the splenial fibers in surgical interventions in patients who exhibit hemianopia.

Background: Standard open techniques for pedicle screws placement require extensive tissue dissection for optimal screw trajectory. Furthermore, they have been associated with extensive blood loss, long hospital stays and, consequently, significant costs. Objective: To describe a percutaneous pedicle screw fixation performed with a novel navigated “one-step” system, underlining the safety and effectiveness of such technique. Methods: During a 43-month period, 43 patients with 230 pedicle screws were evaluated. Percutaneous pedicle screw fixation was performed in the lumbosacral region in 5 patients (12%), lumbar region in 13 (30%), thoraco-lumbar region in 21 (49%) and thoracic region in 4 (9%). We have compared the accuracy rates of screw placement achieved with percutaneous pedicle screw fixation using fluoroscopy, and neuronavigated percutaneous pedicle screw fixation using an innovative “one-step” technique. Results: Statistical differences in screws placement accuracy between the group A and B were evaluated by Fisher exact test. The accuracy rate of pedicle screws placement in group with the intraoperative navigation system was higher than that of the group with fluoroscopy (P = 0.04). There was no hardware failure except 3 screws of Group A (1.3%) that pulled out few weeks after surgery, There were a total of 6 SAR (2.61%) and only 1 of them belonged to group B, without the need of revision surgery (0.61% out of the total neuronavigated stabilizations), while the other 5 represent 7.35% of the total screws placed with fluoroscopy. In our patient series the risk of mispositioning has been reduced by 14.95% with the use of the neuronavigation system, considering as malposition the set of IMP and SAR. Conclusions: Percutaneous pedicle screw fixation with neuronavigated “one-step” technique represents a safe and effective tool in minimally invasive spine surgery that deserves a further investigation and widespread diffusion.

Gliomas represent over 70% of all brain tumors, they are highly invasive and structurally vascular neoplasms. Despite the latest technological advance in neuro-surgery the survival of patients with high-grade glioma remains poor. The lack of robust treatment options has propelled the search for new markers that may able allow the identification of patients who can benefit from molecularly targeted therapies. The Hippo signaling pathway is considered as a key regulator of tissue homeostasis, cell proliferation and apoptosis, and alterations of this pathway seem to contribute to tumorigenesis. Yes-associated protein (YAP1) is a downstream target of the Hippo pathway which acts as a transcription co-activator. In cancer, YAP1 has been reported to function either as an oncogene or tumor suppressor, depending on the cell context. The aim of this study was to examine the expression of YAP1, Survivin and LATS1 kinase activity in human astroglial tumors with different grades of malignancy. Moreover, we also investigated the expression of miR-221 and miR-10b and their relationship with core molecules of the Hippo pathway. Our results showed the overexpression of YAP1 and Survivin as well as a decreased activity of large tumor suppressor 1 (LATS1) in high-grade glioblastoma versus anaplastic astrocytoma and low-grade glioma. Furthermore, we also demonstrated that miR-221 and miR-10b are specifically involved in Hippo signaling via LATS1 regulation and that their knockdown significantly decreased glioma cell proliferation. This preliminary data confirmed the crucial role of the Hippo pathway in cancer and suggested that miR-221 and miR-10b could be potential therapeutic targets for glioma treatment.

Background: Different surgical techniques have been described for treatment of degenerative lumbar stenosis (DLS). Only postoperative measures have been identified as predictors of efficacy of decompression. The objective of this study is to assess the role of navigated unilateral laminotomy with crossover to achieve and predict a satisfying decompression and outcome in DLS. Materials and Methods: We enrolled patients with DLS who underwent navigation-assisted unilateral laminotomy with crossover. The extent of decompression was evaluated during surgery using neuronavigation. The outcome was assessed through the Oswestry disability index (ODI) and visual analog scale (VAS) for leg pain. Outcome correlation with the extent of the intraoperative bone decompression was analyzed. Finally, the outcome, surgical time, and in-hospital length-of-stay were compared with a control group treated through standard unilateral laminotomy. Results: Twenty-five patients were treated using the navigated technique (Group A), 25 using the standard unilateral laminotomy (Group B). In Group A, a cut-off value ≥0.9 cm for bone decompression revealed to be an intraoperative predictor of good outcome, both regarding the ODI and VAS scores (P = 0.0005; P = 0.002). As compared with Group B, patients operated using the navigated technique showed similar operative times, in-hospital length-of-stay, ODI scores, but improved VAS scores for leg pain (P = 0.04). Conclusions: The intraoperative navigated evaluation of the bone decompression could predict the outcome allowing satisfactory results in unilateral laminotomy for DLS. The navigated technique also could lead to an improved decompression of lateral recesses resulting in better control of leg pain as compared to standard unilateral laminotomy.

Background and Objectives: The term acrometastases (AM) refers to secondary lesions sited distally to the elbow and knee, representing 0.1% of all bony metastases. By frequency, pulmonary cancer and gastrointestinal and genitourinary tract neoplasms are the most responsible for the reported AM. Improvements in oncologic patient care favor an increase in the incidence of such rare cases. We performed a systematic review of acrometastases to the hand to provide further insight into the management of these fragile patients. We also present a peculiar case of simultaneous acrometastasis to the ring finger and pathological vertebral fracture. Material and Methods: A literature search according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was conducted using the PubMed, Google Scholar, and Scopus databases in December 2020 on metastasis to the hand and wrist, from 1986 to 2020. MeSH terms included acrometastasis, carpal metastasis, hand metastasis, finger metastasis, phalangeal metastasis, and wrist metastasis. Results: In total, 215 studies reporting the follow-up of 247 patients were analyzed, with a median age of 62 years (range 10–91 years). Overall, 162 out of 247 patients were males (65.6%) and 85 were females (34.4%). The median reported follow-up was 5 months (range 0.5–39). The median time from primary tumor diagnosis to acrometastasis was 24 months (range 0.7–156). Acrometastases were located at the finger/phalanx (68.4%), carpal (14.2%), metacarpal (14.2%), or other sites (3.2%). The primary tumors were pulmonary in 91 patients (36.8%). The average interval from primary tumor diagnosis to acrometastasis varied according to the primary tumor type from 2 months (in patients with mesenchymal tumors) to 64.0 months (in patients with breast cancer). Conclusions: Acrometastases usually develop in the late stage of oncologic disease and are associated with short life expectancy. Their occurrence can no longer be considered rare; physicians should thus be updated on their surgical management and their impact on prognosis and survival.

Aim: The aim of the current study is the description of an emblematic case of a ruptured left temporal arteriovenous malformation (AVM) causing a large intraparenchymal temporo-parietal left hematoma that resulted in a severe retrograde amnesia. Methods: The patient underwent neurosurgical evacuation of the hematoma and resection of the AVM. He was also sumbitted to several pre- and post-operative neuropsychological evaluations and to rehabilitation for different subdomains of both memory and language. Results: At the end of the rehabilitation course, a new neuropsychological assessment was performer together with a functional cortical mapping Navigated Transcranial Magnetic Stimulation (nTMS) to evaluate the focal damage to and the plastic recovery of language cortical areas. Discussion: This case report must be ecologically oriented and based on the relationship between the importance and the nature of the cognitive and type of claims of the specific environment of the individual; that a rehabilitative path cannot ignore a holistic approach that considers the effects of the injury on the emotional and psychosocial states of the person and his family members.

An amendment to this paper has been published and can be accessed via the original article.

BACKGROUND: Telomeres alteration during carcinogenesis and tumor progression has been described in several cancer types. Telomeres length is stabilized by telomerase (h-TERT) and controlled by several proteins that protect telomere integrity, such as the Telomere Repeat-binding Factor (TRF) 1 and 2 and the tankyrase-poli-ADP-ribose polymerase (TANKs-PARP) complex. OBJECTIVE: To investigate telomere dysfunction in astroglial brain tumors we analyzed telomeres length, telomerase activity and the expression of a panel of genes controlling the length and structure of telomeres in tissue samples obtained in vivo from astroglial brain tumors with different grade of malignancy. MATERIALS AND METHODS: Eight Low Grade Astrocytomas (LGA), 11 Anaplastic Astrocytomas (AA) and 11 Glioblastoma Multiforme (GBM) samples were analyzed. Three samples of normal brain tissue (NBT) were used as controls. Telomeres length was assessed through Southern Blotting. Telomerase activity was evaluated by a telomere repeat amplification protocol (TRAP) assay. The expression levels of TRF1, TRF2, h-TERT and TANKs-PARP complex were determined through Immunoblotting and RT-PCR. RESULTS: LGA were featured by an up-regulation of TRF1 and 2 and by shorter telomeres. Conversely, AA and GBM were featured by a down-regulation of TRF1 and 2 and an up-regulation of both telomerase and TANKs-PARP complex. CONCLUSIONS: In human astroglial brain tumours, up-regulation of TRF1 and TRF2 occurs in the early stages of carcinogenesis determining telomeres shortening and genomic instability. In a later stage, up-regulation of PARP-TANKs and telomerase activation may occur together with an ADP-ribosylation of TRF1, causing a reduced ability to bind telomeric DNA, telomeres elongation and tumor malignant progression.