190 results on '"Lorenzo Genitori"'
Search Results
2. Vascular complications in craniopharyngioma-resected paediatric patients: a single-center experience
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Barbara Castelli, Mirko Scagnet, Federico Mussa, Lorenzo Genitori, Iacopo Sardi, and Stefano Stagi
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paediatric neuro-oncology ,craniopharyngioma ,deep venous thrombosis ,vascular complications ,neurosurgery ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
BackgroundCraniopharyngioma (CP), although slow growing and histologically benign, has high morbidity, mostly related to hypothalamus-pituitary dysfunction and electrolyte imbalance. Increased risk of vascular complications has been described. However, data are still poor, especially in the paediatric population. The aim of our study was to evaluate the occurrence, timing, and predisposing factors of deep venous thrombosis (DVT) and other vascular alterations in neurosurgical paediatric CP patients.Materials and MethodsIn a single-centre, retrospective study, we investigated 19 CP patients (11 males, 8 females, mean age 10.5 ± 4.3 years), who underwent neurosurgery between December 2016 and August 2022, referred to Meyer Children’s Hospital IRCCS in Florence.ResultsFive patients (26.3%) presented vascular events, which all occurred in connection with sodium imbalances. Three DVT (two with associated pulmonary embolism, in one case leading to death) developed in the post-operative period, most frequently at 7-10 days. Elevated D-dimers, a reduced partial activated thrombin time and a prolonged C-reactive protein increase were highly related to thrombotic vascular events. One case of posterior cerebral artery pseudoaneurysm was described soon after neurosurgery, requiring vascular stenting. Superficial vein thrombophlebitis was a late complication in one patient with other predisposing factors.ConclusionCP patients undergoing neurosurgery are at risk of developing DVT and vascular alterations, thus careful follow-up is mandatory. In our study, we found that the phase of transition from central diabetes insipidus to a syndrome of inappropriate antidiuretic hormone secretion may be a period of significant risk for DVT occurrence. Careful vascular follow-up is mandatory in CP-operated patients.
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- 2024
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3. Corrigendum: Bevacizumab-Irinotecan combination therapy in recurrent low-grade glioma, previously treated with chemo-radiotherapy: a case report
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Barbara Castelli, Carla Fonte, Milena Guidi, Marco Tellini, Marco Di Nicola, Alessandro Iacono, Anna Maria Buccoliero, Daniela Greto, Lorenzo Genitori, and Iacopo Sardi
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low-grade gliomas ,bevacizumab ,irinotecan ,pilocytic astrocytoma ,case report ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2024
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4. Bevacizumab-Irinotecan combination therapy in recurrent low-grade glioma, previously treated with chemo-radiotherapy: a case report
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Barbara Castelli, Carla Fonte, Milena Guidi, Marco Tellini, Marco Di Nicola, Alessandro Iacono, Anna Maria Buccoliero, Daniela Greto, Lorenzo Genitori, and Iacopo Sardi
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low-grade gliomas ,bevacizumab ,irinotecan ,pilocytic astrocytoma ,case report ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Low grade gliomas (LGGs) of pineal region are usually difficult to remove and they frequently relapse or progress after front line chemotherapy. Bevacizumab-Irinotecan (BEVIRI) combination has been successfully attempted in children with recurrent LGGs, in most cases not previously irradiated. The efficacy of bevacizumab has also been described in radiation necrosis. Considering the possible overlapping of radiation treatment effect and disease progression and difficulty in differentiating, we report on the use of BEVIRI in a case of a recurrent relapsing low-grade glioma of the pineal region, subjected to multiple neurosurgical interventions, also treated with a carboplatin-etoposide regimen and a radiation course, at present at one-year follow-up showing a stable response, with no adverse events.
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- 2023
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5. Laser interstitial thermal therapy (LITT) for pediatric patients affected by intracranial tumors
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Barbara Spacca, Marco Di Maurizio, Manuela Grandoni, Sara Tempesti, and Lorenzo Genitori
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LITT ,laser ,laser interstitial thermal therapy ,brain tumor ,pediatric neuro-oncology ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
IntroductionThe surgical treatment of brain tumors has evolved over time, offering different strategies tailored to patients and their specific lesions. Among these strategies, Laser Interstitial Thermal Therapy (LITT) is one of the most recent advances in pediatric neurooncological surgery, and its results and evolution are still under assessment.MethodsWe retrospectively analyzed data from six pediatric patients with deep-seated brain tumors treated with LITT at a single center between November 2019 and June 2022. A total of four patients underwent a stereotaxic biopsy during the same operating session. The indications and preparation for LITT, technical issues, clinical and radiological follow-up, impact on quality of life, and oncological treatment are discussed.ResultsThe mean patient age eight years (ranging from 2 to 11 years). The lesion was thalamic in four patients, thalamo-peduncular in one, and occipital posterior periventricular in one. In total, two patients had been previously diagnosed with low-grade glioma (LGG). Biopsies revealed LGG in two patients, ganglioglioma grade I in one, and diffuse high-grade glioma (HGG) in one. Postoperatively, two patients presented with transient motor deficits. The mean follow-up period was 17 months (ranging from 5 to 32 months). Radiological follow-up showed a progressive reduction of the tumor in patients with LGG.ConclusionLaser interstitial thermal therapy is a promising, minimally invasive treatment for deep-seated tumors in children. The results of lesion reduction appear to be relevant in LGGs and continue over time. It can be used as an alternative treatment for tumors located at sites that are difficult to access surgically or where other standard treatment options have failed.
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- 2023
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6. Use of High-Dose Chemotherapy in Front-Line Therapy of Infants Aged Less Than 12 Months Treated for Aggressive Brain Tumors
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Milena Guidi, Laura Giunti, Anna Maria Buccoliero, Mariarita Santi, Barbara Spacca, Salvatore De Masi, Lorenzo Genitori, and Iacopo Sardi
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congenital tumor ,chemotherapy ,glioblastoma ,brain tumor ,newborn ,Pediatrics ,RJ1-570 - Abstract
Introduction: Malignant brain tumors in infants less than 12 months of age are extremely rare, and they have poor prognosis. We evaluated genetic characteristics and response rates of infants with congenital brain tumors subjected to high-dose chemotherapy and autologous stem cell transplant after gross total tumor resection.Materials and Methods: In total, 10 infants, aged less than 12 months, were enrolled in this study. The median age was 56 days (range: 1–279 days). Pathological examination demonstrated the following: four anaplastic astrocytomas, two glioblastomas, two central nervous system (CNS) embryonal tumors, not otherwise specified (NOS), and two atypical teratoid/rhabdoid tumors.Results: All patients were exposed to induction chemotherapy regimen, two high-dose chemotherapy courses, and autologous stem cell transplant after maximal surgery. At 1–3–5 years, the global overall survival (OS) was 90, 70, and 70% and the progression-free survival (PFS) was 80–60 and 60%. In all the patients, the copy number variants (CNVs) profile was analyzed using the SNP/CGH array approach. To investigate the clinical relevance of germline SMARCB1 mutation in AT/RT patients, we performed sequence analysis of the coding regions. The two patients with AT/RT were found to have germline SMARCB1 mutations. No BRAF mutations were found, and only NTRK gene fusion was present in one patient. We also have examined the association with OS and PFS and different histological subtypes of infant CNS proving that high-grade astrocytoma has better overall survival than other tumor types (p: 0.007 and p: 0.0590).Conclusion: High-dose chemotherapy regimen represents a valid therapeutic approach for congenital brain tumors with a high rate of response. The molecular analysis has to be analyzed in all infants' brain tumor types. High-grade gliomas are characterized by a better prognosis than other histologies of infant CNS.
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- 2020
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7. Sirolimus in Infants with Multiple Cardiac Rhabdomyomas Associated with Tuberous Sclerosis Complex
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Maurizio Lucchesi, Enrico Chiappa, Flavio Giordano, Francesco Mari, Lorenzo Genitori, and Iacopo Sardi
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mTOR inhibitors ,Sirolimus ,Tuberous sclerosis complex ,Cardiac rhabdomyomas ,Subpendymal giant cell astrocytomas ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: Cardiac rhabdomyomas represent a frequent manifestation of tuberous sclerosis. Tumor growth, mainly prenatally, can result in intrauterine fetal or neonatal deaths in almost 10% of patients. Case Report: We treated 3 consecutive infants aged less than 12 months with sirolimus, an oral mTOR inhibitor. All patients achieved significant reductions in cardiac rhabdomyomas. A complete response was documented in 2 patients, while a partial response with tumor debulking greater than 50% was seen in the other one. The median time to best cardiac response was 1.9 months in all patients, and 3.3 months in those with complete response. The side effects profile was acceptable. Conclusion: Sirolimus may have a significant role in promoting natural regression of cardiac rhabdomyomas. Prospective clinical trials are needed.
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- 2018
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8. Additive Manufacturing and Reverse Engineering in Cranioplasty: A Personalized Approach to Minimize Skin Flap Complications
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Antonio Marzola, Francesco Buonamici, Rocco Furferi, Lapo Governi, Lorenzo Genitori, and Federico Mussa
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cranioplasty ,patient-specific implant ,additive manufacturing ,skull reconstruction ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Cranioplasty is a procedure performed to repair defects in the human skull bone by surgically reconstructing the shape and function of the cranium. Several complications, both intraoperative and postoperative, can affect the procedure’s outcome (e.g., inaccuracies of the reconstructed shape, infections, ulcer, necrosis). Although the design of additive manufactured implants in a preoperative stage has improved the general quality of cranioplasties, potential complications remain significant, especially in the presence of critical skin tissue conditions. In this paper, an innovative procedure to improve the chances of a positive outcome when facing critical conditions in a cranioplasty is described. The proposed approach relies on a structured planning phase articulated in a series of digital analyses and physical simulations performed on personalized medical devices that guide the surgeon in defining surgical cuts and designing the implant. The ultimate goal is to improve the chances of a positive outcome and a fast recovery for the patient. The procedure, described in extenso in the paper, was positively tested on a cranioplasty case study, which presented high risk factors.
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- 2021
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9. Current Practice in Preoperative Virtual and Physical Simulation in Neurosurgery
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Elisa Mussi, Federico Mussa, Chiara Santarelli, Mirko Scagnet, Francesca Uccheddu, Rocco Furferi, Yary Volpe, and Lorenzo Genitori
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neurosurgery ,brain ,cancer ,3d printing ,computer aided design ,3d casting ,additive manufacturing ,virtual planning ,physical simulation ,preoperative planning ,Technology ,Biology (General) ,QH301-705.5 - Abstract
In brain tumor surgery, an appropriate and careful surgical planning process is crucial for surgeons and can determine the success or failure of the surgery. A deep comprehension of spatial relationships between tumor borders and surrounding healthy tissues enables accurate surgical planning that leads to the identification of the optimal and patient-specific surgical strategy. A physical replica of the region of interest is a valuable aid for preoperative planning and simulation, allowing the physician to directly handle the patient’s anatomy and easily study the volumes involved in the surgery. In the literature, different anatomical models, produced with 3D technologies, are reported and several methodologies were proposed. Many of them share the idea that the employment of 3D printing technologies to produce anatomical models can be introduced into standard clinical practice since 3D printing is now considered to be a mature technology. Therefore, the main aim of the paper is to take into account the literature best practices and to describe the current workflow and methodology used to standardize the pre-operative virtual and physical simulation in neurosurgery. The main aim is also to introduce these practices and standards to neurosurgeons and clinical engineers interested in learning and implementing cost-effective in-house preoperative surgical planning processes. To assess the validity of the proposed scheme, four clinical cases of preoperative planning of brain cancer surgery are reported and discussed. Our preliminary results showed that the proposed methodology can be applied effectively in the neurosurgical clinical practice both in terms of affordability and in terms of simulation realism and efficacy.
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- 2020
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10. Surgery of complex craniofacial defects: A single-step AM-based methodology.
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Yary Volpe, Rocco Furferi, Lapo Governi, Francesca Uccheddu, Monica Carfagni, Federico Mussa, Mirko Scagnet, and Lorenzo Genitori
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- 2018
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11. Is endoscope-assisted strip craniectomy the future of metopic suture craniosynostosis treatment? An 11-year experience with 62 patients
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Rina Agushi, Mirko Scagnet, Barbara Spacca, Regina Mura, Manuela Grandoni, Federico Mussa, and Lorenzo Genitori
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General Medicine - Abstract
OBJECTIVE Endoscopic mini-invasive treatment for sporadic trigonocephaly is becoming a widely accepted surgical treatment. In most centers this treatment is performed in association with postoperative helmeting. The aim of the present study was to review and report the authors’ 11-year experience of endoscope-assisted metopic suturectomy for treatment of 62 trigonocephaly patients without helmet use. METHODS For this retrospective study, clinical data of 62 consecutive pediatric patients (age 3–8 months) were obtained from the data bank of the “Anna Meyer” Children Hospital. These patients had been diagnosed with trigonocephaly (type II and III) and undergone surgery performed with a mini-invasive endoscopic technique during the period from January 2011 to January 2022. No helmet was used postoperatively in these patients, and they were evaluated through craniometric measurements, pre-/postoperative photographs, and parents’ impressions, as well as thorough clinical examinations during follow-up appointments. RESULTS The mean patient follow-up period was 6 ± 1.3 years. The female/male ratio was 1:2; 52% of the patients presented with type II trigonocephaly and the remaining patients with type III. The mean age at surgery was 153 ± 44 days (5 ± 1.5 months, range 3–8 months). In 92% of the patients the surgical outcome was defined as good to excellent. However, 4 patients presented with an unsatisfactory outcome, including 1 patient with a CSF collection requiring surgical repair 2 months after the first surgery and 1 patient who developed infection of the surgical wound and needed a second surgery. In the latter patient the outcome was evaluated as satisfactory, and no sequelae regarding the infection were encountered during follow-up. CONCLUSIONS According to the authors’ experience, endoscopic metopic suturectomy alone, without the use of a helmet, is a valid surgical option for trigonocephaly treatment, and its application can be considered in patients of older age groups (up to 8 months). Thus, in the right patient selection context, this technique represents the treatment of choice.
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- 2023
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12. Loculated hydrocephalus: is neuroendoscopy effective and safe? A 90 patients’ case series and literature review
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Alice Noris, Flavio Giordano, Simone Peraio, Matteo Lenge, Regina Mura, Letizia Macconi, Raffaella Barzaghi, and Lorenzo Genitori
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Pediatrics, Perinatology and Child Health ,Neurology (clinical) ,General Medicine - Abstract
Introduction Loculated hydrocephalus is a complex condition in which different non-communicating compartments form within the ventricular system due to different etiology, mainly intraventricular hemorrhage and infection. Since the end of the twentieth century, neuroendoscopy has been explored as a therapeutic option for loculated hydrocephalus with non-univocal results. Methods We performed a retrospective analysis of 90 patients who underwent endoscopic treatment for loculated hydrocephalus from January 1997 to January 2021 (mean age: 2 years, range 7–21). We included 37 (41.1%) children with multiloculated hydrocephalus, 37 (41.1%) with isolated lateral ventricle, 13 (14.4%) with excluded temporal horn, and 3 (3.3%) with isolated fourth ventricle. We compared our results with those available in literature. Results A mean of 1.91 endoscopic procedure/patient were performed (only one endoscopy in 42.2% of cases). Complications of neuroendoscopy and of shunt surgeries were recorded in 17 (18.9%) and 52 (57.8%) children, respectively. Twenty-six (28.9%) children were shunt-free at the last follow-up, 47.8% have only one shunt. Discussion The first goal of neuroendoscopy is to increase the rate of shunt-free patients but, when it is not possible, it aims at simplifying shunt system and reducing the number of surgical procedures. In our series, neuroendoscopy was able to achieve both these goals with an acceptable complication rate. Thus, our results confirmed neuroendoscopy as a valid tool in the long-term management of loculated hydrocephalus. Neuronavigation and intraoperative ultrasound could increase the success rate in cases with distorted anatomy.
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- 2022
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13. La diagnosi di craniostenosi: alcune riflessioni per il pediatra
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Lorenzo Genitori, Mauro Massimetti, and Mirko Scagnet
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Pediatrics, Perinatology and Child Health - Abstract
Microcephaly is a medical condition involving a smaller-than-normal head. Microcephaly may present at birth or it may develop in the first few years of life. Patients with this disorder often have an intellectual disability, poor motor function, poor speech, abnormal facial features and seizures. Microcephaly does not have to suggest exclusively a craniosynostosis. Over the last decade, cranial suture ultrasound has played an increasingly important role in diagnosing craniosynostosis; ultrasound allows a differential diagnosis between craniosynostosis and a positional malformation to be made. A cranial suture is considered normal if a hypoechoic space has been identified between two hyperechoic bony plates. The anterior fontanelle is the largest fontanelle and is placed at the junction of the sagittal suture, coronal suture and frontal suture. The fontanelle allows the skull to deform during birth to ease its passage through the birth canal and for expansion of the brain after birth. The anterior fontanelle can remain open until 18 months. The early closure of the bregmatic fontanelle is never the expression of a craniostenosis, unlike what happens for the fusion of the cranial sutures that are always an indication of craniostenosis.
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- 2022
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14. Algorithm to the treatment of Crouzon syndrome
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Mirco Raffaini, Alice Sara Magri, Lorenzo Genitori, and Francesco Arcuri
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Ossification ,business.industry ,medicine.medical_treatment ,Orthognathic surgery ,Crouzon syndrome ,medicine.disease ,Osteotomy ,Genioplasty ,Craniosynostosis ,Otorhinolaryngology ,Occlusion ,medicine ,Distraction osteogenesis ,Surgery ,Oral Surgery ,medicine.symptom ,business ,Algorithm - Abstract
Clinical reports regarding the entire surgical sequence in Crouzon syndrome from the neonatal period to the adult age are rare. The purpose of this study is to trace an operative algorithm with a long term follow up in a homogenous group of patients affected by Crouzon syndrome. A retrospective review was conducted for all patients affected by Crouzon syndrome who completed the entire surgical sequence. 7 Crouzon patients (4 females, 3 males) completed the entire surgical sequence at different ages: fronto-orbital advancement (0.9 years), LF III distraction osteogenesis (11.5 years) and orthognathic surgery (18 years). The mean age at the last follow up was 19.3 years; normalization of the face was obtained in all cases with improvement of the respiratory problems. After orthognathic surgery, all patients had stable occlusion. A one-year postoperative CBCT scan revealed almost complete ossification of all osteotomy sites. Frontoorbital advancement and modified Le Fort III distraction osteogenesis are reliable surgical procedures. SARME and conventional orthognathic surgery with reductive genioplasty and fat grafting are performed at the end of the surgical sequence to enhance facial aesthetics.
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- 2022
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15. Endoscopic Endonasal Treatment of Intra-Axial Ventral Brainstem Cavernomas: Case Experience and Literature Review
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Paolo Priore, Filippo Giovannetti, Mirko Scagnet, Federico Mussa, Elena Arcovio, Danilo Di Giorgio, Marco Primavera, Valentino Valentini, and Lorenzo Genitori
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Pediatrics, Perinatology and Child Health ,Surgery ,Neurology (clinical) ,General Medicine - Abstract
Introduction: Cavernous malformations of the ventral brainstem are a challenging disease to treat. From an anatomical perspective, the best surgical options are endoscopic endonasal approaches. The first reports of their usage for this purpose date back to 2012. In this study, we gathered data on the subject, share our experience, and outline technical notes and tips for this surgery. Case Presentation: We report a 14-year-old female with a ventral pons cavernoma, treated using an endoscopic endonasal transclival approach and followed-up for 5.9 years. This is the longest reported follow-up for this condition to date. Written informed consent was obtained from the patient for publication of this case report and the accompanying images. Discussion: An endoscopic endonasal transclival approach was used. The skull base was reconstructed using the multilayer grafting technique and a nasoseptal flap. There was no postoperative cerebrospinal fluid leakage. In a literature review, we identified 8 patients who were treated endoscopically: 1 transplanum-transtuberculum, 1 transtuberculum-transclival, and 6 transclival approaches were employed. Skull base closure was achieved using multilayer grafting and a nasoseptal flap in 4 cases, a gasket seal technique combined with nasoseptal flap in 3 cases and a periumbilical fat graft, fibrin sealant patch, and fibrin glue in 1 case. There were 2 cases of leakage, which resolved completely with revision surgery. Conclusion: Endoscopic surgery is a reliable alternative to traditional open surgery. It may be the preferred choice for intra-axial ventral brain cavernomas.
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- 2022
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16. Operational Improvement in Pediatric Neurosurgery
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Barbara Spacca, Davide Luglietto, Octavian Vatavu, Ludovico D’Incerti, Germana Tuccinardi, Desy Butti, Leonardo Bussolin, Federico Mussa, and Lorenzo Genitori
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- 2023
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17. Airgun Wound with Superior Sagittal Sinus Involvement in a Child: Case Report and Review of the Literature
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Flavio Giordano, Alessia Nucci, Lorenzo Genitori, Francesco Salomi, Martina Giacalone, Simone Peraio, and Andrea Di Rita
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Neurological status ,Occipital bone ,General Medicine ,medicine.disease ,Thrombosis ,Surgery ,medicine.anatomical_structure ,Pediatrics, Perinatology and Child Health ,Dural venous sinuses ,Angiography ,medicine ,Rifle ,Neurology (clinical) ,business ,Sinus (anatomy) ,Superior sagittal sinus - Abstract
Introduction: Although still considered quite harmless, nonpowder guns (NPG) may cause severe head injuries in children. We present the case of a depressed skull fracture with superior sagittal sinus involvement following NPG injury. Decision-making and surgical management are discussed, and the current literature concerning NPG-related pediatric head injuries is reviewed. Case Presentation: A 4-year-old boy hit by a compressed-air rifle came to our center. CT scan showed a depressed skull fracture of the occipital bone on the midline and intracranial penetration of some fragments of the pellet. CT angiography documented a compression of the superior sagittal sinus without thrombosis. Soon after hospital admission, the patient showed deterioration of the neurological status suggesting intracranial hypertension. Surgery was performed with fracture elevation, removal of metal fragments, and wound debridement. The patient had a full recovery without subsequent neurological deficits. Discussion/Conclusion: Modern airguns may produce severe penetrating head injuries in children. Parents and physicians should be aware of the danger of NPG. Depressed skull fracture and dural venous sinus involvement can occur, and even a stable neurological condition may worsen. In such instances, a thorough preoperative assessment including vascular imaging is mandatory. The surgical risk is not negligible due to the possible injury of the sinus wall and subsequent intraoperative bleeding. This has to be weighted against potential complications of the penetrating injury, such as infection, sinus thrombosis, and intracranial hypertension. Our case suggests that prompt surgical treatment can be a safe and effective option.
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- 2021
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18. Management of Childhood-onset Craniopharyngioma in Italy: A Multicenter, 7-Year Follow-up Study of 145 Patients
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Daniela Driul, Stefano Tumini, Carlo Efisio Marras, Valentino Cherubini, Natascia Di Iorgi, Stefano Cianfarani, Stefania Pedicelli, Lorenzo Genitori, Mino Zucchelli, Malgorzata Wasniewska, Giovanna Giudica, Marco Vindigni, Cristina Partenope, Chiara Guzzetti, Maria Parpagnoli, Stefano Zucchini, Lorenzo Iughetti, Maria Laura Iezzi, Alessandro Consales, Rachele Menardi, Sandro Loche, Irene Rutigliano, Patrizia Bruzzi, Federico Baronio, Francesco Zenga, Mariafelicia Faienza, Tommaso Aversa, Marco Crocco, Gerdi Tuli, P Matarazzo, Raffaella Di Mase, Mohamad Maghnie, Beatrice Nardini, Claudia Milanaccio, Pietro Mortini, Cristina Baldoli, Graziamaria Ubertini, Anna Grandone, Mariacarolina Salerno, Gabriella Pozzobon, and Alessandra Cassio
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Male ,Pediatrics ,Neoplasm, Residual ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Hypopituitarism ,Biochemistry ,Craniopharyngioma ,Postoperative Complications ,Endocrinology ,Pituitary deficiency ,Recurrence ,Age of Onset ,Child ,Human Growth Hormone ,Follow up studies ,Treatment Outcome ,Italy ,Child, Preschool ,Residual ,Pituitary Gland ,Female ,medicine.symptom ,craniopharyngioma ,GH therapy ,children ,hypothalamic obesity ,intracranial tumor ,pituitary deficiency ,Follow-Up Studies ,Humans ,Hypophysectomy ,Pituitary Neoplasms ,Retrospective Studies ,medicine.medical_specialty ,Pediatric endocrinology ,Context (language use) ,Lesion ,Internal medicine ,medicine ,Preschool ,business.industry ,Biochemistry (medical) ,medicine.disease ,Radiation therapy ,Neoplasm ,business - Abstract
Context Nationwide data on children diagnosed with craniopharyngioma (CP) are not available in Italy. Objective This work aimed to identify patients’ characteristics, type of surgical approach, complications and recurrences, number of pituitary deficits, and number of patients starting growth hormone (GH) treatment. Methods A retrospective multicenter collection took place of 145 patients aged 0 to 18 years who underwent surgery for CP between 2000 and 2018, and followed up in 17 Italian centers of pediatric endocrinology. Results Age at diagnosis was 8.4 ± 4.1 years. Duration of symptoms was 10.8 ± 12.5 months and headache was most frequent (54%), followed by impaired growth (48%) and visual disturbances (44%). Most lesions were suprasellar (85%), and histology was adamantinomatous in all cases but two. Surgical approach was transcranial (TC) in 67.5% of cases and transsphenoidal (TS) in 31.%. The TC approach was prevalent in all age groups. Postsurgery complications occurred in 53% of cases, with water-electrolyte disturbances most frequent. Radiotherapy was used in 39% of cases. All patients but one presented with at least one hormone pituitary deficiency, with thyrotropin deficiency most frequent (98.3%), followed by adrenocorticotropin (96.8%), arginine vasopressin (91.1%), and GH (77.4%). Body mass index (BMI) significantly increased over time. A hypothalamic disturbance was present in 55% of cases. GH therapy was started during follow-up in 112 patients at a mean age of 10.6 years, and 54 developed a recurrence or regrowth of the residual lesion. Conclusion CP is often diagnosed late in Italy, with TC more frequent than the TS surgical approach. Postsurgery complications were not rare, and hypopituitarism developed almost in all cases. BMI shows a tendency to increase overtime.
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- 2021
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19. Exclusive Neurogenic Bladder and Fecal Incontinency in an Achondroplasic Child Successfully Treated with Lumbar Foraminal Decompression
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G.M. Poggi, Regina Mura, Flavio Giordano, Matteo Lenge, Gianpiero Di Giacomo, Maria Taverna, Sabrina Giglio, Pierarturo Donati, Germana Tuccinardi, Lorenzo Genitori, Simone Peraio, Chiara Cini, and Lorenzo Mongardi
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musculoskeletal diseases ,Foramen magnum ,medicine.medical_specialty ,business.industry ,Spinal stenosis ,medicine.medical_treatment ,Laminectomy ,General Medicine ,medicine.disease ,Surgery ,Stenosis ,medicine.anatomical_structure ,Lumbar ,Foraminotomy ,Pediatrics, Perinatology and Child Health ,medicine ,Fecal incontinence ,Neurology (clinical) ,Achondroplasia ,medicine.symptom ,business - Abstract
Introduction: Achondroplasia is a genetic disorder characterized by defects in the development of endochondral bone resulting in skeletal abnormalities like stenosis of the foramen magnum and of the spine, shortened limb bones, and macrocephaly. Congenital spinal stenosis is frequent and due to premature fusion of the pedicles to the laminae. Case Presentation: We report a case of neurogenic bladder and fecal incontinence due to lumbar stenosis successfully treated with L1–L5 partial laminectomy and foraminotomy in a 7-year-old achondroplasic child. Discussion/Conclusion: To our knowledge, this is the first case report of exclusive neurogenic bladder and fecal incontinence in an achondroplasic child. Neurogenic bladder and fecal incontinence without motor impairment may be early and exclusive clinical findings of lumbar stenosis in children with achondroplasia.
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- 2021
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20. Chiari 1 malformation and exome sequencing in 51 trios: the emerging role of rare missense variants in chromatin-remodeling genes
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Flavio Giordano, Viviana Palazzo, Silvia Guarducci, Livia Garavelli, Mirko Scagnet, Angelica Pagliazzi, Marzia Mortilla, Rosangela Artuso, Sabrina Giglio, Daniele di Feo, Orsetta Zuffardi, Giulia Forzano, Gianluca Mattei, Giovanna Traficante, Lucia Tiberi, Betti Giusti, Aldesia Provenzano, Andrea La Barbera, Lorenzo Genitori, Claudio De Filippi, Ada Kura, Nehir Edibe Kurtas, Debora Vergani, Marilena Pantaleo, and Sara Bargiacchi
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Male ,Microcephaly ,Adolescent ,MAP Kinase Signaling System ,Mutation, Missense ,RASopathy ,Biology ,Chromatin remodeling ,Young Adult ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Exome Sequencing ,Genetics ,medicine ,Humans ,Missense mutation ,Child ,Gene ,Genetics (clinical) ,Exome sequencing ,Original Investigation ,030304 developmental biology ,0303 health sciences ,Infant ,Chromatin Assembly and Disassembly ,medicine.disease ,Magnetic Resonance Imaging ,Human genetics ,Arnold-Chiari Malformation ,Child, Preschool ,Mendelian inheritance ,symbols ,Female ,030217 neurology & neurosurgery - Abstract
Type 1 Chiari malformation (C1M) is characterized by cerebellar tonsillar herniation of 3–5 mm or more, the frequency of which is presumably much higher than one in 1000 births, as previously believed. Its etiology remains undefined, although a genetic basis is strongly supported by C1M presence in numerous genetic syndromes associated with different genes. Whole-exome sequencing (WES) in 51 between isolated and syndromic pediatric cases and their relatives was performed after confirmation of the defect by brain magnetic resonance image (MRI). Moreover, in all the cases showing an inherited candidate variant, brain MRI was performed in both parents and not only in the carrier one to investigate whether the defect segregated with the variant. More than half of the variants were Missense and belonged to the same chromatin-remodeling genes whose protein truncation variants are associated with severe neurodevelopmental syndromes. In the remaining cases, variants have been detected in genes with a role in cranial bone sutures, microcephaly, neural tube defects, and RASopathy. This study shows that the frequency of C1M is widely underestimated, in fact many of the variants, in particular those in the chromatin-remodeling genes, were inherited from a parent with C1M, either asymptomatic or with mild symptoms. In addition, C1M is a Mendelian trait, in most cases inherited as dominant. Finally, we demonstrate that modifications of the genes that regulate chromatin architecture can cause localized anatomical alterations, with symptoms of varying degrees. Electronic supplementary material The online version of this article (10.1007/s00439-020-02231-6) contains supplementary material, which is available to authorized users.
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- 2020
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21. Pediatric High Grade Glioma Classification Criteria and Molecular Features of a Case Series
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Anna Maria Buccoliero, Laura Giunti, Selene Moscardi, Francesca Castiglione, Aldesia Provenzano, Iacopo Sardi, Mirko Scagnet, Lorenzo Genitori, and Chiara Caporalini
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Genetics ,Humans ,Glioma ,Child ,Genetics (clinical) ,pediatric ,high-grade glioma ,astrocytoma ,thalamic glioma ,gene panel ,IDH2 mutation ,EZHIP ,TP53 ,H3F3A ,case report - Abstract
Pediatric high-grade gliomas (pHGGs) encompass a heterogeneous group of tumors. Three main molecular types (H3.3 mutant, IDH mutant, and H3.3/IDH wild-type) and a number of subtypes have been identified. We provide an overview of pHGGs and present a mono-institutional series. We studied eleven non-related pHGG samples through a combined approach of routine diagnostic tools and a gene panel. TP53 and H3F3A were the most mutated genes (six patients each, 54%). The third most mutated gene was EGFR (three patients, 27%), followed by PDGFRA and PTEN (two patients each, 18%). Variants in the EZHIP, MSH2, IDH1, IDH2, TERT, HRAS, NF1, BRAF, ATRX, and PIK3CA genes were relatively infrequent (one patient each, 9%). In one case, gene panel analysis documented the presence of a pathogenic IDH2 variant (c.419G>A, p.Arg140Gln) never described in gliomas. More than one-third of patients carry a variant in a gene associated with tumor-predisposing syndromes. The absence of constitutional DNA did not allow us to identify their constitutional origin.
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- 2022
22. Pediatric colloid cysts: a multinational, multicenter study. An IFNE-ISPN-ESPN collaboration
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Jonathan Roth, Yurii Perekopaiko, Danil A. Kozyrev, Shlomi Constantini, Hannah E. Myers, Benjamin L. Chern, Andrew Reisner, Jose Hinojosa Mena-Bernal, Andrea Bartoli, Luca Paun, Saqib Kamran Bakhshi, M Shahzad Shamim, Giuseppe Talamonti, R. Michael Scott, Nir Shimony, Ahmed El Damaty, Rodrigo Mierez, José Silva, Gustavo Sánchez, Andrea Di Rita, Lorenzo Genitori, Barbara Spacca, Yacine Felissi, Abdelhalim Morsli, Giselle Cardozo-Faust, Dhaval Shukla, Dwarakanath Srinivas, Kevin Jude Sudevan, Meriem Amarouche, J. André Grotenhuis, Hieronymus D. Boogaarts, Javier Márquez-Rivas, Mónica Rivero-Garvia, Philippe De Vloo, Frank Van Calenbergh, Henry W. S. Schroeder, Sascha Marx, Ehab El Refaee, Onur Ozgural, Eyüp Bayatli, Gökmen Kahiloğulları, Jayaratnam Jayamohan, Francesco T. Mangano, Jesse M. Skoch, Sudhakar Vadivelu, Charles B. Stevenson, Ricardo Brandao Fonseca, Igor Faquini, Mosaab Alsuwaihel, P. Daniel McNeely, Alexandre Varella Giannetti, Katalin Lorincz, Martin Schuhmann, Sandrine de-Ribaupierre, William C. Gump, Flavio Giordano, George I. Jallo, John Goodden, Ieva Sataite, Domenico Catapano, Ulrich-W. Thomale, Matthias Schulz, Luca Massimi, Gianpiero Tamburrini, Giuseppe Cinalli, Pietro Spennato, and Vincent Jecko
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colloid cyst ,oncology ,General Medicine ,endoscopy ,hydrocephalus - Abstract
OBJECTIVE Colloid cysts (CCs) are rare at all ages, and particularly among children. The current literature on pediatric CC is limited, and often included in mixed adult/pediatric series. The goal of this multinational, multicenter study was to combine forces among centers and investigate the clinical course of pediatric CCs. METHODS A multinational, multicenter retrospective study was performed to attain a large sample size, focusing on CC diagnosis in patients younger than 18 years of age. Collected data included clinical presentation, radiological characteristics, treatment, and outcome. RESULTS One hundred thirty-four children with CCs were included. Patient age at diagnosis ranged from 2.4 to 18 years (mean 12.8 ± 3.4 years, median 13.2 years, interquartile range 10.3–15.4 years; 22% were < 10 years of age). Twenty-two cases (16%) were diagnosed incidentally, including 48% of those younger than 10 years of age. Most of the other patients had symptoms related to increased intracranial pressure and hydrocephalus. The average follow-up duration for the entire group was 49.5 ± 45.8 months. Fifty-nine patients were initially followed, of whom 28 were eventually operated on at a mean of 19 ± 32 months later due to cyst growth, increasing hydrocephalus, and/or new symptoms. There was a clear correlation between larger cysts and symptomatology, acuteness of symptoms, hydrocephalus, and need for surgery. Older age was also associated with the need for surgery. One hundred three children (77%) underwent cyst resection, 60% using a purely endoscopic approach. There was 1 death related to acute hydrocephalus at presentation. Ten percent of operated patients had some form of complication, and 7.7% of operated cases required a shunt at some point during follow-up. Functional outcome was good; however, the need for immediate surgery was associated with educational limitations. Twenty operated cases (20%) experienced a recurrence of their CC at a mean of 38 ± 46 months after the primary surgery. The CC recurrence rate was 24% following endoscopic resection and 15% following open resections (p = 0.28). CONCLUSIONS CCs may present in all pediatric age groups, although most that are symptomatic present after the age of 10 years. Incidentally discovered cysts should be closely followed, as many may grow, leading to hydrocephalus and other new symptoms. Presentation of CC may be acute and may cause life-threatening conditions related to hydrocephalus, necessitating urgent treatment. The outcome of treated children with CCs is favorable.
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- 2022
23. Clinical-pathological study of 28 glial and mixed neuronal-glial tumors diagnosed within the first year of life
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Mirko Scagnet, Selene Moscardi, Chiara Caporalini, Iacopo Sardi, Lorenzo Genitori, Anna Maria Buccoliero, Francesca Castiglione, Barbara Spacca, and Laura Giunti
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Pathology ,medicine.medical_specialty ,Adolescent ,Astrocytoma ,Pathology and Forensic Medicine ,medicine ,Subependymal zone ,Humans ,Gangliocytoma ,Child ,neoplasms ,Ganglioglioma ,Pilocytic astrocytoma ,business.industry ,Brain Neoplasms ,Not Otherwise Specified ,General Medicine ,Glioma ,medicine.disease ,nervous system diseases ,nervous system ,Neurology ,Giant cell ,Immunohistochemistry ,Neurology (clinical) ,business ,Glioblastoma ,Anaplastic astrocytoma - Abstract
Our purpose was to investigate the incidence of gliomas and neuronal-glial tumors, their outcome, and H3.3K27M, BRAFV600E, and IDH status in children within 1 year of age affected by CNS tumor. We collected 28 consecutive gliomas and mixed tumors. Immunohistochemistry and/or molecular analyses were performed on formalin-fixed/paraffin-embedded specimens. 24 (86%) tumors were supratentorial. 15 (54%) tumors were astrocytomas (5 glioblastomas, 1 anaplastic astrocytoma, 1 pilocytic astrocytoma, 3 pilomixoid astrocytomas, 2 subependymal giant cell astrocytomas, 3 astrocytomas not otherwise specified (NOS)), 4 (14%) were anaplastic ependymomas, and 9 (32%) were mixed tumors (5 gangliogliomas, 2 gangliocytomas, 2 desmoplastic infantile gangliogliomas (DIGs)). Alive patients were: 4 (67%) affected by high-grade astrocytoma (mean follow-up 64 months), 4 (67%) affected by low-grade astrocytoma (mean follow-up 83 months), 2 (67%) affected by astrocytoma NOS (mean follow-up 60 months), 1 (25%) affected by anaplastic ependymoma (follow-up 12 months), and 9 (100%) affected by mixed tumors (mean follow-up 74 months). H3.3K27M and IDH were not-mutated in any tumor (100%). BRAFV600E mutation was documented in 6 (21%) tumors (4 gangliogliomas, 1 gangliocytoma, and 1 astrocytoma NOS resulted as anaplastic pleomorphic xanthoastrocytoma 8 years later). Gliomas and mixed tumors diagnosed within 1 year of age are morphologically heterogeneous. Moreover, analogously to those affecting older children, they are IDH1-2 and H3.3K27M (when located outside midline) not-mutated while BRAFV600E mutation is typical of gangliogliomas/gangliocytomas and pleomorphic xanthoastrocytomas. High-grade astrocytomas have a more favorable prognosis compared with the same lesions occurring later in life while ependymomas have a poorer outcome.
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- 2021
24. Deep Brain Stimulation of Subgenual Cingulate Region for Treatment of an Early-Onset Conversion Disorder with Psychogenic Non-Epileptic Seizures and Prolonged Catatonia: Preliminary Results in One Patient
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Tiziana Pisano, Sara Gori, Lorenzo Genitori, Lorenzo Mongardi, Flavio Giordano, Sara Minghetti, Matteo Lenge, Stelvio Sestini, and Michele Alessandro Cavallo
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Deep brain stimulation ,business.industry ,Catatonia ,medicine.medical_treatment ,medicine.disease ,Cingulate region ,Anesthesia ,Psychogenic non-epileptic seizures ,medicine ,Surgery ,Neurology (clinical) ,business ,Conversion disorder ,Early onset - Published
- 2021
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25. Complete section of the left vagus nerve does not preclude the efficacy of vagus nerve stimulation: illustrative case
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Flavio Giordano, Andrea Di Rita, Matteo Lenge, Lorenzo Genitori, Anna Zicca, Simone Peraio, Alice Noris, and Paolo Roncon
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Epilepsy ,Left vagus nerve ,business.industry ,medicine.medical_treatment ,Section (typography) ,medicine ,General Medicine ,Anatomy ,medicine.disease ,business ,Vagus nerve stimulation - Abstract
BACKGROUND Vagus nerve stimulation (VNS) represents a valid therapeutic option for patients with medically intractable seizures who are not candidates for epilepsy surgery. Even when complete section of the nerve occurs, stimulation applied cranially to the involved nerve segment does not preclude the efficacy of VNS. Complete vagus nerve section with neuroma causing definitive left vocal cord palsy has never been previously reported in the literature. OBSERVATIONS Eight years after VNS implant, the patient experienced worsening of seizures; the interrogation of the generator revealed high impedance requiring surgical revision. On surgical exploration, complete left vagus nerve section and a neuroma were found. Vocal cord atrophy was found at immediate postoperative laryngeal inspection as a confirmation of a longstanding lesion. Both of these events might have been caused by direct nerve injury during VNS surgery, and they presented in a delayed fashion. LESSONS VNS surgery may be complicated by direct damage to the left vagus nerve, resulting in permanent neurological deficits. A complete section of the nerve also enables an efficacious stimulation if applied cranially to the involved segment. Laryngeal examination should be routinely performed before each VNS surgery to rule out preexisting vocal cord dysfunction.
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- 2021
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26. A Semi-Automatic Hybrid Approach for Defective Skulls Reconstruction
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Rocco Furferi, Yary Volpe, Federico Mussa, Antonio Marzola, Lapo Governi, and Lorenzo Genitori
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Reverse engineering ,Engineering drawing ,Computer science ,medicine.medical_treatment ,Computational Mechanics ,CAD ,Hybrid approach ,computer.software_genre ,Computer Graphics and Computer-Aided Design ,Cranioplasty ,Computational Mathematics ,medicine ,Semi automatic ,computer - Published
- 2019
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27. Respiratory and volumetric changes of the upper airways in craniofacial synostosis patients
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Giuseppe Spinelli, Barbara Spacca, Lorenzo Genitori, Giuditta Mannelli, and Francesco Arcuri
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Polysomnography ,medicine.medical_treatment ,Population ,Osteogenesis, Distraction ,Facial Bones ,Craniosynostoses ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Osteotomy, Le Fort ,Respiratory system ,Craniofacial ,Child ,education ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Respiration ,Infant ,030206 dentistry ,Airway obstruction ,Synostosis ,medicine.disease ,respiratory tract diseases ,Treatment Outcome ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,Anesthesia ,Distraction osteogenesis ,Surgery ,Oral Surgery ,Airway ,business - Abstract
To assess postoperative changes of the upper airway in a pediatric syndromic cranial-synostosis (SCS) population who underwent Le Fort III (LFIII) or frontofacial advancement by distraction osteogenesis (DO). Charts' review of 25 SCS infants presented at our tertiary-care children's hospital between January 2005 and December 2016 was performed. Preoperative (T0) and postoperative (T1) three-dimensional computed tomography (3D-CT) and polysomnography (PSG) were recorded. Differences between T0 and T1 airway volumes and changes in PSG data were analyzed. 18 patients were included. The mean T0 and T1 volumes were calculated as 15.963 mm3 ± 7.181 SD and 24.550 mm3 ± 12.946 SD, respectively. Airway areas increased significantly (p A statistically significant gain of the upper airway after LF III and DO in SCS patients has been demonstrated. Given the absence of a direct relationship between post-operative upper airway volume increase and OSAS degree improvement, further insights should consider performing T0 and T1 sleep endoscopy analysis to complete the diagnostic workup and to better assess the level of residual or recurrent upper airway obstruction in patients who experience unsuccessful surgical treatment.
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- 2019
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28. Outcome after hemispherotomy in patients with intractable epilepsy: Comparison of techniques in the Italian experience
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Renzo Guerrini, Carlo Efisio Marras, Flavio Giordano, Camilla Rossi-Espagnet, Lorenzo Genitori, Carmen Barba, Massimo Cossu, Federico Vigevano, Laura Tassi, Nicola Pietrafusa, Giorgio Lo Russo, Susanna Rizzi, Veronica Pelliccia, Nicola Specchio, Alessandro De Benedictis, Luca De Palma, Francesca Gozzo, and Giusy Carfi-Pavia
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Adult ,Male ,Drug Resistant Epilepsy ,Hemimegalencephaly ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Hemispherectomy ,Young Adult ,03 medical and health sciences ,Behavioral Neuroscience ,Epilepsy ,Postoperative Complications ,0302 clinical medicine ,Recurrence ,medicine ,Humans ,Epilepsy surgery ,030212 general & internal medicine ,Child ,Encephalomalacia ,Retrospective Studies ,business.industry ,Infant ,Cortical dysplasia ,medicine.disease ,Treatment Outcome ,Italy ,Neurology ,Child, Preschool ,Cohort ,Etiology ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
The objective of the study was to evaluate clinical characteristics and outcome of hemispherotomy in children and adolescents with hemispheric refractory epilepsy in an Italian cohort of patients.We retrospectively evaluated the clinical course and outcome of 92 patients with refractory epilepsy who underwent hemispherotomy in three Italian epilepsy centers between 2006 and 2016. Three different approaches for hemispherotomy were used: parasagittal, modified parasagittal, and lateral.Mean age at epilepsy onset was 1.8 ± 2.51 years, and mean duration of epilepsy prior to surgery was 7.4 ± 5.6 years. Mean age at surgery was 9.2 ± 8.0 years. After a mean follow-up of 2.81 ± 2.4 years, 66 of 90 patients (two lost from follow-up, 73.3%) were seizure-free (Engel class I). The etiology of epilepsy was related to acquired lesions (encephalomalacia or gliosis) in 44 patients (47.8%), congenital malformations (cortical dysplasia, hemimegalencephaly, other cortical malformations) in 38 (41.3%), and progressive conditions (Rasmussen or Sturge-Weber syndrome) in 10 patients (10.9%). Regarding seizure outcome, we could not identify statistically significant differences between vertical and lateral approaches (p = 0.154). Seizure outcome was not statistically different in patients with congenital vs acquired or progressive etiologies (p = 0.43). Acute postoperative seizures (APOS) correlated with poor outcome (p 0.05). On multivariate analysis, presurgical focal to bilateral tonic-clonic seizures (Odds Ratio (OR) = 3.63, 95% Confidence Interval (CI): 1.86-15.20, p = 0.048) independently predicted seizure recurrence. Twenty-one patients (22.8%) exhibited postoperative complications, with no unexpected and persistent neurological deficit. More than 50% of the patients completely tapered drugs.Our data confirm hemispherotomy to be a safe and effective procedure in patients with drug resistant epilepsies due to hemispheric lesions. Presurgical focal to bilateral tonic-clonic seizures are the strongest predictor of seizure recurrence after surgery, independently from the type of hemispherotomy.
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- 2019
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29. Primary Intracerebral Alveolar Soft Part Sarcoma: Report of a Case and Review of the Literature
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Anna Maria Buccoliero, Chiara Caporalini, Giampiero Di Giacomo, Selene Moscardi, Rita Alaggio, Regina Mura, Gioia Di Stefano, Iacopo Sardi, Matteo Lenge, Mirko Scagnet, Lorenzo Genitori, Massimo Basile, Angelica Zin, and Flavio Giordano
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Pathology ,medicine.medical_specialty ,Adolescent ,Central nervous system ,Soft Tissue Neoplasms ,Pathology and Forensic Medicine ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Female patient ,Alveolar soft part sarcoma ,Medicine ,Humans ,Pathological ,business.industry ,Soft tissue ,medicine.disease ,Primary Alveolar Soft Part Sarcoma ,Molecular analysis ,medicine.anatomical_structure ,Sarcoma, Alveolar Soft Part ,030220 oncology & carcinogenesis ,Surgery ,Female ,Anatomy ,Differential diagnosis ,business ,030217 neurology & neurosurgery - Abstract
Alveolar soft part sarcomas (ASPSs) are rare malignant tumors representing ∼1% of all soft tissue sarcomas. Most ASPS occurring in the central nervous system are metastases. In contrast, primary intracranial ASPSs are extremely rare and only 8 cases have been previously reported in English literature. Here, we report a case of primary alveolar soft part sarcoma in a 16-year-old female patient with no evidence of primary extracranial tumors. Histologically this case fulfilled the criteria of ASPS, and a molecular confirmation has been archived. To date, only 9 primary intracranial ASPS cases, including ours, have been reported in the literature. This report highlights the clinical and pathological characteristics, differential diagnosis, and molecular analysis of primary ASPS of the central nervous system.
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- 2021
30. Distinct DNA Methylation Patterns of Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex
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Wiesława Grajkowska, Roland Coras, Wilfred F. A. den Dunnen, Anika Bongaarts, Theresa Scholl, Sergiusz Jozwiak, Brendon P. Scicluna, Antoinette Y N Schouten-van Meeteren, José Pimentel, Figen Soylemezoglu, Johannes A. Hainfellner, Eleonora Aronica, Jasper J. Anink, Wim G.M. Spliet, David T.W. Jones, Anna Maria Buccoliero, Chiara Caporalini, Angelika Mühlebner, Ingmar Blümcke, James D. Mills, Victoria E Gruber, Martha Feucht, Caroline Mijnsbergen, Katarzyna Kotulska, Floor E. Jansen, Lorenzo Genitori, Werner Paulus, Flavio Giordano, Graduate School, APH - Aging & Later Life, APH - Mental Health, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Pathology, Center of Experimental and Molecular Medicine, Epidemiology and Data Science, Paediatric Oncology, and Molecular Neuroscience and Ageing Research (MOLAR)
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Low-grade glioma ,RNA-sequencing ,Gliomas -- Treatment ,Biology ,Leukocyte mediated immunity ,Astrocytoma ,Methylation ,SEGA ,Cellular and Molecular Neuroscience ,Tuberous Sclerosis ,medicine ,Humans ,Vitamin A ,Extracellular structure organization ,TSC ,Sirolimus ,Tuberous sclerosis ,Cell Biology ,General Medicine ,DNA Methylation ,Acquired immune system ,Carotenoids ,medicine.anatomical_structure ,DNA methylation ,Cancer research ,TSC1 ,TSC2 ,RNA -- Biotechnology ,Extracellular matrix organization - Abstract
Tuberous sclerosis complex (TSC) is a monogenic disorder caused by mutations in either the TSC1 or TSC2 gene, two key regulators of the mechanistic target of the rapamycin complex pathway. Phenotypically, this leads to growth and formation of hamartomas in several organs, including the brain. Subependymal giant cell astrocytomas (SEGAs) are low-grade brain tumors commonly associated with TSC. Recently, gene expression studies provided evidence that the immune system, the MAPK pathway and extracellular matrix organization play an important role in SEGA development. However, the precise mechanisms behind the gene expression changes in SEGA are still largely unknown, providing a potential role for DNA methylation. We investigated the methylation profile of SEGAs using the Illumina Infinium HumanMethylation450 BeadChip (SEGAs n = 42, periventricular control n = 8). The SEGA methylation profile was enriched for the adaptive immune system, T cell activation, leukocyte mediated immunity, extracellular structure organization and the ERK1 & ERK2 cascade. More interestingly, we identified two subgroups in the SEGA methylation data and show that the differentially expressed genes between the two subgroups are related to the MAPK cascade and adaptive immune response. Overall, this study shows that the immune system, the MAPK pathway and extracellular matrix organization are also affected on DNA methylation level, suggesting that therapeutic intervention on DNA level could be useful for these specific pathways in SEGA. Moreover, we identified two subgroups in SEGA that seem to be driven by changes in the adaptive immune response and MAPK pathway and could potentially hold predictive information on target treatment response., peer-reviewed
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- 2021
31. Angiocentric glioma-associated seizures: The possible role of EATT2, pyruvate carboxylase and glutamine synthetase
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Sabrina Rossi, Felice Giangaspero, Anna Maria Buccoliero, Marco Gessi, Lorenzo Genitori, Mariarita Santi, Flavio Giordano, Luca Bertero, Eleonora Aronica, Mirko Scagnet, Selene Moscardi, Vittoria Donofrio, Federico Mussa, Carmen Barba, Valerio Conti, Irene Migliastro, Chiara Caporalini, Francesca Gianno, Francesca Diomedi-Camassei, Renzo Guerrini, Iacopo Sardi, Manila Antonelli, Pathology, APH - Aging & Later Life, APH - Mental Health, and Amsterdam Neuroscience - Cellular & Molecular Mechanisms
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LEAT ,Angiocentric Glioma ,Glutamic Acid ,Pathogenesis ,03 medical and health sciences ,Epilepsy ,Brain ,Central nervous system ,Tumor ,Glutamate-Ammonia Ligase ,Humans ,Pyruvate Carboxylase ,Glioma ,Seizures ,0302 clinical medicine ,Glutamine synthetase ,medicine ,Chemistry ,Glutamate receptor ,General Medicine ,Glutamic acid ,medicine.disease ,Pyruvate carboxylase ,Neurology ,Cancer research ,Neurology (clinical) ,030217 neurology & neurosurgery - Abstract
Purpose Our purpose was to better understand the pathogenesis of seizures associated with angiocentric glioma. Angiocentric glioma is an indolent and rare low-grade glioma. Its typical clinical presentation is with epileptic seizures. The pathogenesis of tumor-associated seizures is poorly understood. Among the possible pathomechanisms, the increased neurotoxic concentrations of the glutamate has been proposed. Glutamate transporters, pyruvate carboxylase and glutamine synthetase are involved in maintaining the physiological concentration of glutamate in the inter synaptic spaces. Methods We evaluated the immunohistochemical expression of EAAT2 (the most important glutamate transporter), pyruvate carboxylase and glutamine synthetase in 17 angiocentric gliomas. Results EAAT2 was never expressed (0%) in the neoplastic cells in none of the cases studied. Pyruvate carboxylase was expressed in the cytoplasm of the neoplastic cells in 16/17 cases (94 %). Glutamine synthetase was expressed in the cytoplasm of the neoplastic cells in 15/17 cases (88 %). Conclusion The net result of this enzymatic expression, in particular considering the loss of EAAT2, could be an increased glutamate concentration in the synaptic clef, which might increase local network excitability initially involving intratumoral neurons. The observation that the angiocentric glioma-associated epilepsy might be at least in part related to EAAT2 deficiency opens up interesting therapeutic perspectives.
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- 2021
32. Genetic signature and treatment of pediatric high-grade glioma
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Luisa Galli, Anna Maria Buccoliero, Laura Giunti, Milena Guidi, Lorenzo Genitori, M Censullo, Iacopo Sardi, and Chiara Caporalini
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Cancer ,Articles ,medicine.disease ,Malignancy ,Genetic analysis ,Molecular medicine ,03 medical and health sciences ,Histone H3 ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Glioma ,Internal medicine ,Mutation (genetic algorithm) ,medicine ,030211 gastroenterology & hepatology ,business ,Anaplastic astrocytoma - Abstract
Pediatric high-grade glioma (HGG) is a type of malignancy that carries a poor prognosis. The genetic analysis of HGGs has previously identified useful mutations, the targeting of which has improved prognosis. Thus, further research into the more common mutations, such as H3 histone variants (HIST1H3B and H3F3A) and BRAF V600E, may be useful in identifying tumors with different prognoses, as the mutations are considered to drive two distinct oncogenic programs. The present study performed a retrospective analysis of pediatric HGGs. In total, 42 cases of HGG, including 32 cases (76.1%) of anaplastic astrocytoma and 10 cases (23.8%) of glioblastoma multiforme (GBM), were assessed. The median age of the patients was 7 years (range, 0-32 years). Mutations on histone H3, in particular the K27M and G34R mutations in the distinct variants HIST1H3B and H3F3A, in addition to the presence of the BRAF V600E mutation, were analyzed in 24 patients. The H3F3A K27M mutation was identified in 7 patients (29.1%), while the HIST1H3B K27M mutation was only observed in 1 patient with GBM. In addition, 5 patients harbored a BRAF V600E mutation (21%), while the H3F3A G34R mutation was not recorded in any of the patients. The overall survival of the wild-type patients at 20 months was 68% [confidence interval (CI): 38-85%] compared with 28% (CI: 0.4-60%) in patients with the H3F3A K27M mutation. These results suggested that patients with the H3F3A K27M mutation had a worse prognosis compared with wild-type patients (P=0.0045). Moreover, 3/5 patients with the BRAF V600E mutation had HGGs that were derived from a previous low-grade glioma (LGG; P=0.001). In conclusion, these results suggested that histone H3 mutations may help predict the outcome in patients with HGG. In addition, the BRAF V600E mutation was found to be associated with an increased risk of anaplastic progression. The novel data of the present study may help better define the clinical and radiological characteristics of glioma.
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- 2021
33. GCT-01. Pediatric intracranial germ cell tumors and primary polyuria-polydipsia syndrome: a 13-year single institutional experience
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Rossana Pavone, Carla Fonte, Franco Ricci, Gaia Varriale, Giorgia Enrico, Maria Luigia Censullo, Carlotta Gemma Gori, Milena Guidi, Anna Maria Buccoliero, Chiara Caporalini, Lorenzo Genitori, and Iacopo Sardi
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Cancer Research ,Oncology ,Neurology (clinical) - Abstract
Intracranial germ cell tumors (IGCTs) represent about 4% of all childhood brain tumors. They are common in both the pineal and pituitary regions and sometimes they can be bifocal. Suprasellar and bifocal IGCTs usually present stereotypical symptoms, including primary polyuria-polydipsia syndrome (PPS). Consolidated IGCTs’ therapy is based on the International Society of Pediatric Oncologic (SIOP) CNS GCT II protocol consisting of primary pre-radiation chemotherapy combining etoposide, carboplatin and/or cisplatin and ifosfamide. PPS management in these patients requires monitoring of electrolytes and fluids during chemotherapy, especially for cisplatin and/or ifosfamide-based cycles, for which hyperhydratation is required. We report the results of our single-center cohort of patients with IGCTs treated between 2008 and 2021, focusing on the clinical presentation, treatment and long-term follow-up. Thirty-one patients were analyzed (median age=13 years, 87% male). Twelve children (39%) presented a PPS and needed desmopressin treatment, maintained at long-term follow-up data update in all. Over these PPS patients, 6 had bifocal germinomas, 4 suprasellar germinomas, 1 metastatic germinoma and 1 non-germinomatous IGCT. Eleven PPS children (92%) received cisplatin and/or ifosfamide-based chemotherapy: all of them had optimal biochemical urine and blood investigations before, during and after chemotherapy. None of them presented serious complications during treatment. After a median follow-up of 5 years, two patients (6.5%) died (1 IGCT-related, 1 non-cancer related) and one had a second malignancy (parotid gland mucoepidermoid carcinoma, 6 years after IGCT diagnosis). Childhood IGCTs have an excellent prognosis, but present a significant risk of long-lasting severe endocrine sequelae which may be worsened by the primary oncological strategy, requiring careful management of complications related to fluid and electrolytes disturbances. In order to avoid post-treatment pituitary insufficiency, guidelines for diabetes insipidus management when cisplatin and/or ifosfamide-based protocols are used should be established and all patients should receive meticulous endocrine follow-up.
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- 2022
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34. Dysregulation of the MMP/TIMP Proteolytic System in Subependymal Giant Cell Astrocytomas in Patients With Tuberous Sclerosis Complex: Modulation of MMP by MicroRNA-320d In Vitro
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Wiesława Grajkowska, Johannes A. Hainfellner, Julita Borkowska, Wim G.M. Spliet, Floor E. Jansen, Angelika Mühlebner, Anika Bongaarts, Caroline Mijnsbergen, Lorenzo Genitori, Jackelien van Scheppingen, Chiara Caporalini, Katarzyna Kotulska, Jasper J. Anink, Theresa Scholl, Sergiusz Jozwiak, Jody M de Jong, Flavio Giordano, Diede W. M. Broekaart, Brendon P. Scicluna, Erwin A. van Vliet, Martha Feucht, Eleonora Aronica, Antoinette Y. N. Schouten-van Meeteren, Anna Maria Buccoliero, James D. Mills, Victoria E Gruber, Wilfred F. A. den Dunnen, Molecular Neuroscience and Ageing Research (MOLAR), Cellular and Computational Neuroscience (SILS, FNWI), Graduate School, Pathology, APH - Aging & Later Life, APH - Mental Health, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Center of Experimental and Molecular Medicine, Epidemiology and Data Science, and Paediatric Oncology
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Male ,MMP2 ,MATRIX METALLOPROTEINASES ,Matrix metalloproteinase ,CORTICAL TUBERS ,Extracellular matrix ,ACTIVATION ,0302 clinical medicine ,Tuberous Sclerosis ,Gene expression ,BRAIN ,Child ,Cells, Cultured ,GENE-EXPRESSION ,0303 health sciences ,Tissue Inhibitor of Metalloproteinases ,MicroRNA ,General Medicine ,Metalloproteinases ,TUMORS ,medicine.anatomical_structure ,Neurology ,Subependymal giant cell astrocytoma (SEGA) ,Child, Preschool ,Giant cell tumors ,Female ,Adult ,Adolescent ,MIGRATION ,Biology ,Astrocytoma ,Pathology and Forensic Medicine ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Young Adult ,microRNA ,medicine ,Subependymal zone ,Humans ,030304 developmental biology ,Tuberous sclerosis ,CENTRAL-NERVOUS-SYSTEM ,MATRIX-METALLOPROTEINASE-9 ,Infant ,Original Articles ,TSC1 ,MicroRNAs ,Tuberous sclerosis complex ,Proteolysis ,Cancer research ,Neurology (clinical) ,TSC2 ,Extracellular matrix -- Metabolism ,030217 neurology & neurosurgery - Abstract
Tuberous sclerosis complex (TSC), a rare genetic disorder caused by a mutation in the TSC1 or TSC2 gene, is characterized by the growth of hamartomas in several organs. This includes the growth of low-grade brain tumors, known as subependymal giant cell astrocytomas (SEGA). Previous studies have shown differential expression of genes related to the extracellular matrix in SEGA. Matrix metalloproteinases (MMPs), and their tissue inhibitors (TIMPs) are responsible for remodeling the extracellular matrix and are associated with tumorigenesis. This study aimed to investigate the MMP/TIMP proteolytic system in SEGA and the regulation of MMPs by microRNAs, which are important post-transcriptional regulators of gene expression. We investigated the expression of MMPs and TIMPs using previously produced RNA-Sequencing data, real-time quantitative PCR and immunohistochemistry in TSC-SEGA samples and controls. We found altered expression of several MMPs and TIMPs in SEGA compared to controls. We identified the lowly expressed miR-320d in SEGA as a potential regulator of MMPs, which can decrease MMP2 expression in human fetal astrocyte cultures. This study provides evidence of a dysregulated MMP/TIMP proteolytic system in SEGA of which MMP2 could be rescued by microRNA-320d. Therefore, further elucidating microRNA-mediated MMP regulation may provide insights into SEGA pathogenesis and identify novel therapeutic targets., peer-reviewed
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- 2020
35. Neurosurgical treatment of subependymal giant cell astrocytomas in tuberous sclerosis complex: a series of 44 surgical procedures in 31 patients
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Flavio Giordano, Renzo Guerrini, Matteo Lenge, Francesco Mari, Lorenzo Mongardi, Anna Maria Buccoliero, Eleonora Aronica, Carla Moscheo, Iacopo Sardi, Roberto Biagiotti, Lorenzo Genitori, Pathology, ANS - Cellular & Molecular Mechanisms, APH - Aging & Later Life, and APH - Mental Health
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medicine.medical_specialty ,mTOR inhibitors ,Astrocytoma ,03 medical and health sciences ,Tuberous sclerosis ,0302 clinical medicine ,Tuberous Sclerosis ,Subependymal zone ,medicine ,Humans ,030212 general & internal medicine ,Child ,Retrospective Studies ,Tuberous sclerosis complex (TSC) ,Tumor size ,business.industry ,Brain Neoplasms ,General Medicine ,Surgical procedures ,Discovery and development of mTOR inhibitors ,medicine.disease ,Hydrocephalus ,Surgery ,Subependymal giant cell astrocytoma (SEGA) ,Giant cell ,Pediatrics, Perinatology and Child Health ,Neurology (clinical) ,Neurosurgery ,Neoplasm Recurrence, Local ,business ,030217 neurology & neurosurgery - Abstract
Background: Subependymal giant cell astrocytomas (SEGA) are benign tumors characteristic of tuberous sclerosis complex (TSC) that may cause hydrocephalus. Various treatments are nowadays available as mTOR inhibitors or surgery. Surgery is still a valid option especially for symptomatic and larger tumors. Methods: From January 1994 to December 2015, 31 TSC patients harboring SEGA underwent surgery at the Department of Neurosurgery of the Meyer Pediatric Hospital, Florence. Indications for surgery were tumor size and location, growth and cystization/hemorrhage, and hydrocephalus. Clinical data, preoperative and postoperative MRI, recurrence rate, further surgical procedures, and related complications were analyzed. Results: A total of 44 surgeries were performed in 31 TSC patients affected by SEGA, achieving gross total removal (GTR) and subtotal removal (STR), respectively, in 36 and 8 patients. Recurrences occurred in 11 patients; 9 of them underwent further surgical procedures and 2 were treated with mTOR pathway inhibitors. Surgical morbidity and mortality were, respectively, 22.7% and 2.3%. After a mean follow-up of 4.9 years, 90% of patients were tumor-free with good neurological status in 93.3%; twelve (40%) had a ventriculo-peritoneal shunt (VPS) for hydrocephalus. Conclusions: The present series confirms that the surgical approach, combined with mTOR inhibitors, is still a valid option for the treatment of SEGAs.
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- 2020
36. Post-mortem histopathology of a pediatric brain after bilateral DBS of GPI for status dystonicus: case report and review of the literature
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Leonardo Lelli, Matteo Lenge, Lorenzo Mongardi, Michele Alessandro Cavallo, Michele Pennica, Simone Peraio, Chiara Caporalini, Regina Mura, Manuela L'Erario, Lorenzo Genitori, Flavio Giordano, Federico Melani, and Anna Maria Buccoliero
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0301 basic medicine ,Male ,medicine.medical_specialty ,Pathology ,Deep brain stimulation ,medicine.medical_treatment ,Deep Brain Stimulation ,Autopsy ,Globus Pallidus ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Child ,business.industry ,CD68 ,General Medicine ,medicine.disease ,Status dystonicus ,030104 developmental biology ,Treatment Outcome ,nervous system ,Gliosis ,Giant cell ,Pediatrics, Perinatology and Child Health ,Histopathology ,Neurology (clinical) ,Astrocytosis ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
To investigate the effects of deep brain stimulation (DBS) electrodes on the brain of a dystonic pediatric patient submitted to bilateral DBS of the globus pallidus internus (GPI). An 8-year-old male patient underwent bilateral DBS of GPI for status dystonicus. He died 2 months later due to multiorgan failure triggered by bacterial pneumonia. A post-mortem pathological study of the brain was done. At visual inspection, no grossly apparent softening, hemorrhage, or necrosis of the brain adjacent to the DBS lead tracts was detected. High-power microscopic examination of the tissue surrounding the electrode trajectories showed lymphocyte infiltration, astrocytic gliosis, microglia, macrophages, and clusters of multinucleate giant cells. Significant astrocytosis was confirmed by GFAP staining in the electrode site. The T cell lymphocyte activity was overexpressed with activated macrophages detected with CD3, CD20, CD45, and CD68 stains respectively. There was no gliosis or leukocyte infiltration away from the surgical tracks of the electrodes. This is the first post-mortem examination of a child’s brain after bilateral DBS of GPI. The comparison with adult post-mortem reports showed no significant differences and confirms the safety of DBS implantation in the pediatric population too.
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- 2020
37. Use of High-Dose Chemotherapy in Front-Line Therapy of Infants Aged Less Than 12 Months Treated for Aggressive Brain Tumors
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Mariarita Santi, Salvatore De Masi, Lorenzo Genitori, Barbara Spacca, Iacopo Sardi, Anna Maria Buccoliero, Milena Guidi, and Laura Giunti
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Brain tumor ,030204 cardiovascular system & hematology ,chemotherapy ,Pediatrics ,03 medical and health sciences ,0302 clinical medicine ,newborn ,030225 pediatrics ,Internal medicine ,medicine ,Original Research ,Chemotherapy ,business.industry ,Not Otherwise Specified ,glioblastoma ,lcsh:RJ1-570 ,Induction chemotherapy ,Astrocytoma ,lcsh:Pediatrics ,medicine.disease ,Chemotherapy regimen ,Regimen ,congenital tumor ,Pediatrics, Perinatology and Child Health ,business ,brain tumor ,Anaplastic astrocytoma - Abstract
Introduction: Malignant brain tumors in infants less than 12 months of age are extremely rare, and they have poor prognosis. We evaluated genetic characteristics and response rates of infants with congenital brain tumors subjected to high-dose chemotherapy and autologous stem cell transplant after gross total tumor resection. Materials and Methods: In total, 10 infants, aged less than 12 months, were enrolled in this study. The median age was 56 days (range: 1-279 days). Pathological examination demonstrated the following: four anaplastic astrocytomas, two glioblastomas, two central nervous system (CNS) embryonal tumors, not otherwise specified (NOS), and two atypical teratoid/rhabdoid tumors. Results: All patients were exposed to induction chemotherapy regimen, two high-dose chemotherapy courses, and autologous stem cell transplant after maximal surgery. At 1-3-5 years, the global overall survival (OS) was 90, 70, and 70% and the progression-free survival (PFS) was 80-60 and 60%. In all the patients, the copy number variants (CNVs) profile was analyzed using the SNP/CGH array approach. To investigate the clinical relevance of germline SMARCB1 mutation in AT/RT patients, we performed sequence analysis of the coding regions. The two patients with AT/RT were found to have germline SMARCB1 mutations. No BRAF mutations were found, and only NTRK gene fusion was present in one patient. We also have examined the association with OS and PFS and different histological subtypes of infant CNS proving that high-grade astrocytoma has better overall survival than other tumor types (p: 0.007 and p: 0.0590). Conclusion: High-dose chemotherapy regimen represents a valid therapeutic approach for congenital brain tumors with a high rate of response. The molecular analysis has to be analyzed in all infants' brain tumor types. High-grade gliomas are characterized by a better prognosis than other histologies of infant CNS.
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- 2020
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38. Endoscopic sinus and skullbase surgery in pediatric patients during the COVID-19 pandemic
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Federico Mussa, Paolo Priore, Ingrid Raponi, Filippo Giovannetti, Mirko Scagnet, Valentino Valentini, and Lorenzo Genitori
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2019-20 coronavirus outbreak ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,SARS-CoV-2 ,business.industry ,General surgery ,Incidence (epidemiology) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Clinical Neurology ,MEDLINE ,COVID-19 ,Endoscopy ,General Medicine ,medicine.anatomical_structure ,Paranasal Sinuses ,Pandemic ,medicine ,Humans ,Surgery ,Neurology (clinical) ,Child ,business ,Pandemics ,Sinus (anatomy) ,Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA - Abstract
To the EditorOn February 20, 2020, the incidence of Covid-19 began to rapidly escalate in Italy. By March 10th, the government announced many restriction measures, hopefully effective for contagiou...
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- 2020
39. Neurosurgery Case Review: Questions and Answers
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Christian A. Bowers, Flavio Giordano, Faisal Abdulhamid Farrash, Pascal M. Jabbour, Alan Siu, Ramez Malak, Donald C. Shields, Unwar Ul-Haq, Jared J. Marks, Francisco Sanz, Achal Patel, Edward C. Benzel, Nabeel S. Alshafai, Hasel W. Slone, Jason S. Goldberg, Fahad Eid Alotaibi, Mohammad Almubaslat, Kamlesh B. Patel, Glenn C. Hunter, Anna Zicca, Michel Lacroix, Ibrahim Althubaiti, H. Francis Farhadi, Ahmed Mohyeldin, Robert L. Tiel, Homoud Aldahash, Claude-Edouard Châtillon, Franco DeMonte, Ossama Al-Mefty, Roberto Rafael Herrera, Nicholas J. Erickson, Nazer H. Qureshi, André Beer-Furlan, Judith Marcoux, Abdulrahman Yaqub Alturki, Ahmed Alaqeel, Badih Daou, Turki Elarjani, Sandeep Mittal, Kathleen E. Knudson, Alvin Chan, Amin B. Kassam, Kelsey A. Walsh, Mohammed Alghamd, Alfio Spina, Richard Bucholz, Fred Gentili, Marguerite Harding, Ricardo L. Carrau, Alwin Camacho, Pablo González-López, Faisal Al-Otaibi, Cristian Gragnaniello, Abdulrahman J. Sabbagh, Asem Salma, Stephen J. Hentschel, Joung H. Lee, Fahad AlKherayf, Rory Mayer, Rihaf Algain, John Woulfe, Stephen M. Russell, Han Zhuang Beh, Perry S. Bradford, Andrew Smith, Frederick Boop, Jorge E. Isaza, Vishal Patel, Eddie Perkins, Abdulrahman Albakr, Ibrahim Omeis, Christopher D. Baggott, Kevin Petrecca, Bassem Yousef Sheikh, Shaymaa Al-Umran, Michele Bailo, Jonathon Lebovitz, Pratap Chand, Edgar Gerardo Ordóñez-Rubiano, Aaron S. Gaekwad, Mohammed Almekhlafi, Jonathan Yun, Dimitri Sigounas, Julius July, Joseph A. Shehadi, Gustavo D. Luzardo, Ennio Antonio Chiocca, Shaan M. Raza, Alberto L. Gallotti, Anup Aggarwal, Ali Luqman, Mohammad A. Aziz-Sultan, Isabella Esposito, Eka Julianta Wahjoepramono, Imad N. Kanaan, Abdulrazag Ajlan, Hosam Al-Jehani, Brian Gill, Jaime Gasco, Brian Seaman, William T. Couldwell, José Luis Ledesma, Gary L. Gallia, Ananth K. Vellimana, Mark G. Hamilton, Da’Marcus Baymon, Almunder Algird, Evan S. Marlin, Ahmad I. Lary, Rudiger Von Ritschl, Afnan Uthman Alkhotani, Kevin Phan, Ayman Abdullah Albanyan, Essam A. Al Shail, Joshua Loewenstein, Mohammad Misfer Alshardan, Denis Klironomos, Ehtesham Ghani, Hector P. Rojas, Jeffery Atkinson, Matthew D. Smyth, Eldad J. Hadar, Erol Veznedaroglu, Mark A. Mahan, Qasim Al Hinai, Iván Verdú-Martínez, Peter J. Mews, Mohamed A. Labib, Randy L. Jensen, Rahul Shah, Amal Mokeem, Rolando Del Maestro, Denis Sirhan, Albert M. Isaacs, José Luis Montes, Mariam Alrashid, Jason Tullis, Hussam Abou-Al-Shaar, Justin Reagan, Daniel S. Ikeda, Pietro Mortini, David Sinclair, Hubert Lee, Mazda K. Turel, Michael S. Taccone, Alexander Y. Lin, Stephano Chang, Patrick Kim, Paul Steinbok, Luke G. F. Smith, Sami Obaid, Ashwag Al-Qurashi, Andrew Shaw, Abdul Haseeb Naeem, Exequiel P. Verdier, Ahmed Jaman Alzahrani, Lahbib A. Soualmi, Remi Nader, Ralph J. Mobbs, Soha Abdu M. Alomar, Mohammed Saeed Bafaqeeh, Zachary N. Litvack, Weston T. Northam, Joaquin Hidalgo, Robert F. Keating, Amgad S. Hanna, Jared Fridley, Bassam M. J. Addas, Monish Maharaj, Diana Ghinda, Daniel M. Prevedello, John S. Myseros, Lorenzo Genitori, Layla Batarfi, Khalid N. Almusrea, Samer K. Elbabaa, Adam Sauh Gee Wu, Anthony M. T. Chau, Naif M. Alotaibi, Saleh S. Baeesa, Kimberly Hamilton, Franz L. Ricklefs, Hashem Al Hashemi, Lissa Marie Peeling, Gareth Rutter, Sohum Desai, Philippe Mercier, Daniel Branch, Jorge E. Alvernia, Craig C. Weinkauf, Sunil Kukreja, Michel W. Bojanowski, Paul W. Gidley, Reem Bunyan, Domenic P. Esposito, Salah Baz, Randall C. Edgell, Christopher Evan Stewart, Burak Sade, Frank Gerold, Ali Alwadei, Nancy McLaughlin, Christopher J. Winfree, Terence Verla, Marc-Elie Nader, Andrew Jea, Filippo Gagliardi, Jean-Pierre Farmer, Giuliana Rizzo, Jeffrey P. Mullin, Ahmed T. Abdelmoity, Eric P. Roger, Anish Sen, Ivona Nemeiko, Mahmoud AlYamany, Anthony J. Caputy, Peter Nakaji, Nirmeen Zagzoog, Charles B. Agbi, Khalid Bajunaid, Matthew Pierson, Juan Ortega-Barnett, Justine Pearl, Maqsood Ahmad, Abdulmajeed Alahmari, and Robert A. Moumdjian
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Questions and answers ,medicine.medical_specialty ,Medical education ,business.industry ,medicine ,Neurosurgery ,business ,Neuroscience ,Case review - Published
- 2020
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40. Reverse Engineering Techniques for Virtual Reconstruction of Defective Skulls: an Overview of Existing Approaches
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Federico Mussa, Yary Volpe, Francesco Buonamici, Rocco Furferi, Antonio Marzola, Lapo Governi, and Lorenzo Genitori
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Reverse engineering ,Engineering drawing ,Computer science ,medicine.medical_treatment ,Computational Mechanics ,CAD ,02 engineering and technology ,021001 nanoscience & nanotechnology ,computer.software_genre ,Computer Graphics and Computer-Aided Design ,Cranioplasty ,Computational Mathematics ,Virtual reconstruction ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,020201 artificial intelligence & image processing ,0210 nano-technology ,computer - Published
- 2018
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41. Dysembryoplastic neuroepithelial tumors: A single-institutional series with special reference to glutamine synthetase expression
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Carmen Barba, Anna Maria Buccoliero, Federico Mussa, Gianna Baroni, Chiara Caporalini, Selene Moscardi, Iacopo Sardi, Mirko Scagnet, Gioia Di Stefano, Lorenzo Genitori, and Flavio Giordano
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Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Adolescent ,Central nervous system ,Biology ,Pathology and Forensic Medicine ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Glutamate-Ammonia Ligase ,Glutamine synthetase ,medicine ,Humans ,Neoplasm ,Premovement neuronal activity ,Child ,Neurons ,Brain Neoplasms ,Glutamate receptor ,Glioma ,General Medicine ,medicine.disease ,Immunohistochemistry ,Neoplasms, Neuroepithelial ,Glutamine ,030104 developmental biology ,medicine.anatomical_structure ,Cerebral cortex ,Astrocytes ,Child, Preschool ,030220 oncology & carcinogenesis ,Cancer research ,Female - Abstract
Dysembryoplastic neuroepithelial tumors (DNT) is a benign (World Health Organisation, WHO, grade I) glioneuronal tumor and it represent one of the most frequent neoplasm in patient affected by seizures. The epileptic neuronal activity can be determined by abnormal synchronization, excessive glutamate excitation and\or inadequate GABA inhibition. Increasing evidence suggests that the astrocytes might be involved in this process even if neurons play a relevant role. In particular astrocytes promote the clearance of glutamate, a potent excitatory neurotransmitter of the central nervous system. Indeed, elevated concentrations of extracellular glutamate may determine iper-excitability and seizures as well as other neurological disorders. So, astrocytes, converting glutamate into glutamine via the enzyme glutamine synthetase (GS), could play a protective anti-seizures role. In the present study, we analyzed the immunohistochemical expression of GS in 20 DNTs specimens documenting a constant immunoistochemical expression of GS in astrocytes of the lesional tissue and of the cerebral cortex.
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- 2021
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42. Corrigendum to ‘Angiocentric glioma-associated seizures: The possible role of EATT2, pyruvate carboxylase and glutamine synthetase [Seizure: European Journal of Epilepsy 86 (2021) 152-154]
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Sabrina Rossi, Valerio Conti, Francesca Diomedi-Camassei, Manila Antonelli, Flavio Giordano, Carmen Barba, Luca Bertero, Anna Maria Buccoliero, Lorenzo Genitori, Federico Mussa, Vittoria Donofrio, Iacopo Sardi, Eleonora Aronica, Felice Giangaspero, Irene Migliastro, Selene Moscardi, Mariarita Santi, Marco Gessi, Renzo Guerrini, Chiara Caporalini, Francesca Gianno, and Mirko Scagnet
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Epilepsy ,Neurology ,Angiocentric Glioma ,Glutamine synthetase ,Cancer research ,medicine ,Neurology (clinical) ,General Medicine ,Biology ,medicine.disease ,Pyruvate carboxylase - Published
- 2021
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43. P06.07 Germline mutation of SMARCE1 gene in a family with spinal meningiomas
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Laura Giunti, Lorenzo Genitori, Anna Lisa Iorio, V Serio, G Casati, E Fiorentini, Annamaria Buccoliero, A Marturano, B Rinaldi, and Iacopo Sardi
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Cancer Research ,Germline mutation ,Oncology ,Spinal Meningiomas ,Cancer research ,Neurology (clinical) ,Biology ,SMARCE1 Gene - Abstract
BACKGROUND Meningioma is the most common benign primary intracranial tumor, arising from arachnoid cells of the meninges, but in 20% of cases displays aggressive behavior. Meningiomas are mainly sporadic and the familial forms are very rare. Meningioma account for a small subset (1–4%) of all pediatric brain tumors and may be associated with hereditary tumor predisposition syndrome caused by germline mutations of NF2, SMARCB1, SUFU, and SMARCE1 genes. MATERIAL AND METHODS We present a case of a 16-year-old girl with spinal clear cell meningiomas (CCMs) WHO II with a second spinal lesion identified during the follow-up. Considering the multiple lesions, we performed Whole Exome Sequencing (WES) on DNA from peripheral blood to search for an underlying CCMs tumor predisposition syndrome (#607174). RESULTS We identified a heterozygous frameshift variant c.439delA (p.Ser147fs) in SMARCE1, chromatin remodelling factor that acts as a tumor suppressor gene. Meningioma analysis by Sanger sequencing showed a loss of heterozygosity (LOH) of the wild-type allele. We identified the c.439delA in the constitutional DNA of the father and the sister but not in the mother. At the moment, the father is asymptomatic and the 14 years old sister showed two spinal lesions (meningiomas likely) at the first MRI. CONCLUSION We report a family study of hereditary tumor predisposition syndrome to CCMs with SMARCE1 mutation in which are present two asymptomatic carriers with different ages and gender. The asymptomatic carriers will undergo neurological examination and MRI of the brain and spine, according to a screening protocol. The incomplete penetrance phenomenon is known in SMARCE1-related families with CCMs and it is probably due to the interaction of SMARCE1 with yet unidentified genes.
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- 2021
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44. Cavernomas intracranianos na infância
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Sérgio Cavalheiro, Pablo Boillot, Lorenzo Genitori, and Gabriel Lena Mauricio Choux
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Surgical resection ,medicine.medical_specialty ,business.industry ,Cavernous angiomas ,Medicine ,Rare Lesion ,Radiology ,Frontal region ,business ,Intracranial Cavernous Angioma - Abstract
Os autores apresentam 14 casos de angiomas cavernosos tratados no Serviço de Neurocirurgia Pediátrica do Hospital des Enfants de La Timone, Marselha, França. Todos os pacientes foram operados e tiveram a confirmação anatomopatológica baseada nos critérios estabelecidos por Russel e Rubinstein. Os resultados foram comparados com 88 casos de angiomas cavernosos, no grupo pediátrico, coletados na literatura. No total de 102 casos, os autores puderam concluir que os angiomas constituem 1 7% das malformações vasculares cerebrais da infância. A localização mais frequente foi a frontal e o hemisfério direito o mais acometido. As formas familiares corresponderam a 6,8% dos casos e 50% destes pacientes apresentavam lesões múltiplas. O tratamento dos cavernomas sintomáticos é cirúrgico, mesmo para as localizações profundas.
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- 2017
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45. Tumor response of temozolomide in combination with morphine in a xenograft model of human glioblastoma
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Anna Lisa Iorio, Giacomo Laffi, Maurizio de Martino, Francesco Cardile, Lorenzo Genitori, Claudio Pisano, Martina Da Ros, Maurizio Lucchesi, Fabiana Colelli, Iacopo Sardi, and Giacomo Signorino
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Animal model ,Blood-brain barrier ,Glioblastoma ,Morphine ,Temozolomide ,temozolomide ,Pharmacology ,Blood–brain barrier ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Internal medicine ,medicine ,Chemotherapy ,business.industry ,animal model ,glioblastoma ,morphine ,blood-brain barrier ,medicine.disease ,Radiation therapy ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Toxicity ,business ,Research Paper ,medicine.drug - Abstract
// Anna Lisa Iorio 1 , Martina da Ros 1 , Lorenzo Genitori 1 , Maurizio Lucchesi 1 , Fabiana Colelli 2 , Giacomo Signorino 2 , Francesco Cardile 2 , Giacomo Laffi 3 , Maurizio de Martino 1 , Claudio Pisano 2 and Iacopo Sardi 1 1 Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children’s Hospital, Florence, Italy 2 BIOGEM Research Institute, Ariano Irpino, Italy 3 Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy Correspondence to: Iacopo Sardi, email: iacopo.sardi@meyer.it Keywords: temozolomide, glioblastoma, morphine, blood-brain barrier, animal model Received: November 15, 2016 Accepted: July 13, 2017 Published: August 03, 2017 ABSTRACT Despite multimodal treatments comprising, radiation therapy (RT) and chemotherapy with temozolomide (TMZ), the prognosis of glioblastoma multiforme (GBM) remains dismal and consolidated therapy yields a median survival of 14.6 months. Blood Brain Barrier (BBB) mediated chemoresistance and high dose related toxicity make necessary the development of new therapeutic approach to sensitize GBM to TMZ. The aim of the present study was to investigate the potential of the treatment morphine plus TMZ metronmic doses (1,77 and 0,9 mg/kg) in GBM therapy. The effect of morphine, on tumor cell growth and P-glycoprothein (P-gp) activity, was investigate in in vitro models. The results demonstrated that GBM cells growth is not influenced by morphine treatment and, for the first time, we show that morphine is an inhibitor of the activity of P-gp efflux transporter who is markedly expressed on BBB. In vivo , response to the treatments TMZ plus morphine was investigated in an orthotopic nude mice model of GBM. Animals treated with TMZ metronomic doses showed a significant tumor growth inhibition compared to untreated mice and association with morphine appears to improve TMZ efficacy. Moreover, the combination of morphine with lower dose of TMZ result in a cytostatic effect on tumor growth over the period of the pharmacological treatments. In conclusion this novel approach could be a successful strategy to overcome chemoresistance and side effects TMZ mediated, reducing drug dosage and improving long term response, in GBM therapy.
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- 2017
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46. Vagus nerve stimulation: Surgical technique of implantation and revision and related morbidity
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Flavio Giordano, Carmen Barba, Lorenzo Genitori, Renzo Guerrini, and Anna Zicca
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Adult ,Male ,Adolescent ,Vagus Nerve Stimulation ,medicine.medical_treatment ,Vocal Cords ,Young Adult ,03 medical and health sciences ,Epilepsy ,0302 clinical medicine ,Blunt dissection ,Bradycardia ,Paralysis ,medicine ,Humans ,Epilepsy surgery ,Phrenic nerve ,Palsy ,business.industry ,Arrhythmias, Cardiac ,medicine.disease ,Electrodes, Implanted ,Vagus nerve ,Neurology ,030220 oncology & carcinogenesis ,Anesthesia ,Equipment Failure ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Vagus nerve stimulation - Abstract
Summary Indications for vagus nerve stimulation (VNS) therapy include focal, multifocal epilepsy, drop attacks (tonic/atonic seizures), Lennox-Gastaut syndrome, tuberous sclerosis complex (TSC)–related multifocal epilepsy, and unsuccessful resective surgery. Surgical outcome is about 50–60% for seizures control, and may also improve mood, cognition, and memory. On this basis, VNS has also been proposed for the treatment of major depression and Alzheimer's' disease. The vagus nerve stimulator must be implanted with blunt technique on the left side to avoid cardiac side effects through the classic approach for anterior cervical discectomy. The actual device is composed of a wire with three helical contacts (two active contacts, one anchoring) and a one-pin battery. VNS is usually started 2 weeks after implantation with recommended settings of stimulation (1.0–2.0 mA; 500 μs pulse width; 20–30 Hz; 30 s ON, 5 min OFF). The complications of VNS therapy are early (related to surgery) and late (related to the device and to stimulation of the vagus nerve). Early complications include the following: intraoperative bradycardia and asystole during lead impedance testing, peritracheal hematoma, infections (3–8%), and vagus nerve injury followed by hoarseness, dyspnea, and dysphagia because of left vocal cord paralysis. Delayed morbidity due to the device includes late infections or problems in wound healing; other more rare events are due to late injury of the nerve. Late complications due to nerve stimulation include delayed arrhythmias, laryngopharyngeal dysfunction (hoarseness, dyspnea, and coughing), obstructive sleep apnea, stimulation of phrenic nerve, tonsillar pain mimicking glossopharyngeal neuralgia, and vocal cord damage during prolonged endotracheal intubation. The laryngopharyngeal dysfunction occurs in about 66% of patients and is usually transitory and due to the stimulation of the inferior (recurrent) laryngeal nerve. A true late paralysis of the left vocal cord is often partial and rare (1–2.7%), and usually transitory, and may be caused by previous surgical trauma (i.e., damage of nerve fibers and/or of their blood supply) or to a supposed chronic denervation during stimulation. Surgery for complete removal or revision and replacement of the device is to be considered in cases of device malfunction (4–16.8%), failure of VNS therapy, intolerable side effects, or because of patient's specific request. As described in the literature, the surgical techniques of lead revision and replacement are two: sharp and blunt dissection of helical electrodes and replacement; and blunt dissection combined with ultrasharp low-voltage cautery dissection. The incidence of left vocal cord palsy after vagus nerve stimulator replacement/revision is slightly higher than that of first implantation (4.9% vs. 3.8%). A de novo implantation in a naive segment of the left or right vagus nerve may be considered in specific cases; the use of the right vagus nerve is a rare exception that may be chosen with an acceptable result.
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- 2017
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47. Current Practice in Preoperative Virtual and Physical Simulation in Neurosurgery
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Yary Volpe, Rocco Furferi, Federico Mussa, Mirko Scagnet, Elisa Mussi, Chiara Santarelli, Francesca Uccheddu, and Lorenzo Genitori
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medicine.medical_specialty ,Computer science ,Process (engineering) ,Best practice ,brain ,Mature technology ,Bioengineering ,lcsh:Technology ,Surgical planning ,Article ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,medicine ,3D casting ,cancer ,Medical physics ,virtual planning ,neurosurgery ,lcsh:QH301-705.5 ,lcsh:T ,computer aided design ,3D printing ,additive manufacturing ,physical simulation ,preoperative planning ,Comprehension ,Identification (information) ,Workflow ,lcsh:Biology (General) ,Neurosurgery ,030217 neurology & neurosurgery - Abstract
In brain tumor surgery, an appropriate and careful surgical planning process is crucial for surgeons and can determine the success or failure of the surgery. A deep comprehension of spatial relationships between tumor borders and surrounding healthy tissues enables accurate surgical planning that leads to the identification of the optimal and patient-specific surgical strategy. A physical replica of the region of interest is a valuable aid for preoperative planning and simulation, allowing the physician to directly handle the patient&rsquo, s anatomy and easily study the volumes involved in the surgery. In the literature, different anatomical models, produced with 3D technologies, are reported and several methodologies were proposed. Many of them share the idea that the employment of 3D printing technologies to produce anatomical models can be introduced into standard clinical practice since 3D printing is now considered to be a mature technology. Therefore, the main aim of the paper is to take into account the literature best practices and to describe the current workflow and methodology used to standardize the pre-operative virtual and physical simulation in neurosurgery. The main aim is also to introduce these practices and standards to neurosurgeons and clinical engineers interested in learning and implementing cost-effective in-house preoperative surgical planning processes. To assess the validity of the proposed scheme, four clinical cases of preoperative planning of brain cancer surgery are reported and discussed. Our preliminary results showed that the proposed methodology can be applied effectively in the neurosurgical clinical practice both in terms of affordability and in terms of simulation realism and efficacy.
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- 2019
48. Genomic Analysis of Dysembryoplastic Neuroepithelial Tumor Spectrum Reveals a Diversity of Molecular Alterations Dysregulating the MAPK and PI3K/mTOR Pathways
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Lea F. Surrey, Adam C. Resnick, Anna Maria Buccoliero, Marilyn M. Li, Joshua Straka, Lorenzo Genitori, Payal Jain, Xiaonan Zhao, Angela J. Waanders, Bo Zhang, Brian N Harding, Phillip B Storm, and Mariarita Santi
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Adult ,Male ,Adolescent ,MAP Kinase Signaling System ,PDGFRA ,medicine.disease_cause ,Pathology and Forensic Medicine ,Fusion gene ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Phosphatidylinositol 3-Kinases ,Young Adult ,0302 clinical medicine ,medicine ,Humans ,Copy-number variation ,Child ,PI3K/AKT/mTOR pathway ,030304 developmental biology ,0303 health sciences ,Mutation ,Phosphoinositide 3-kinase ,biology ,Brain Neoplasms ,Dysembryoplastic Neuroepithelial Tumor ,TOR Serine-Threonine Kinases ,Brain ,General Medicine ,Genomics ,Neoplasms, Neuroepithelial ,Progression-Free Survival ,Neuroepithelial cell ,Neurology ,Child, Preschool ,biology.protein ,Cancer research ,Female ,Neurology (clinical) ,030217 neurology & neurosurgery - Abstract
Dysembryoplastic neuroepithelial tumors (DNT) lacking key diagnostic criteria are challenging to diagnose and sometimes fall into the broader category of mixed neuronal-glial tumors (MNGT) or the recently described polymorphous low-grade neuroepithelial tumor of the young (PLNTY). We examined 41 patients with DNT, MNGT, or PLNTY for histologic features, genomic findings, and progression-free survival (PFS). Genomic analysis included sequence and copy number variants and RNA-sequencing. Classic DNT (n = 26) was compared with those with diffuse growth without cortical nodules (n = 15), 6 of which exhibited impressive CD34 staining classifying them as PLNTY. Genomic analysis was complete in 33, with sequence alterations recurrently identified in BRAF, FGFR1, NF1, and PDGFRA, as well as 7 fusion genes involving FGFR2, FGFR1, NTRK2, and BRAF. Genetic alterations did not distinguish between MNGTs, DNTs, or PLNTYs; however, FGFR1 alterations were confined to DNT, and PLNTYs contained BRAF V600E or FGFR2 fusion genes. Analysis of PFS showed no significant difference by histology or genetic alteration; however, numbers were small and follow-up time short. Further molecular characterization of a PLNTY-related gene fusion, FGFR2-CTNNA3, demonstrated oncogenic potential via MAPK/PI3K/mTOR pathway activation. Overall, DNT-MNGT spectrum tumors exhibit diverse genomic alterations, with more than half (19/33) leading to MAPK/PI3K pathway alterations.
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- 2019
49. P14.46 SUBEPENDYMAL GIANT CELLS ASTROCYTOMA (SEGA) IN TUBEROUS SCLEROSIS COMPLEX (TSC): A SERIES OF 31 PATIENTS
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Lorenzo Genitori, M Grandoni, Milena Guidi, C Moscheo, Annamaria Buccoliero, Flavio Giordano, Iacopo Sardi, Francesco Mari, and Matteo Lenge
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Cancer Research ,Pathology ,medicine.medical_specialty ,Tumor size ,business.industry ,Astrocytoma ,medicine.disease ,Hydrocephalus ,nervous system diseases ,Poster Presentations ,Tuberous sclerosis ,Oncology ,Giant cell ,Subependymal zone ,Medicine ,Neurology (clinical) ,business ,Benign neoplasms ,Intracranial pressure - Abstract
Background Subependymal Giant Cells Astrocytomas (SEGAs) are characteristic of Tuberous Sclerosis Complex (TSC). They are usually benign tumors but may rapidly grow and cause hydrocephalus and raised intracranial pressure. Surgery is mandatory for large and symptomatic SEGAs METHODS 31 patients harboring SEGAs in TSC were admitted for surgery. The main indications for surgery were tumor size and location, tumoral growth and cystization/hemorrhage, and hydrocephalus. In presence of symptomatic hydrocephalus firts surgery aimed to reduce intracranial pressure RESULTS Forty-four surgeries were performed in 31 patients achieving Gross Total and Subtotal Removal in 36 and 8 patients respectively. Recurrences occurred in 11 patients; nine of them were reoperated while two were administered therapy with m-TOR pathway inhibitors. Surgical morbidity and mortality accounted for 22.7% and 2.3% respectively; hydrocephalus was the main complication. After an average follow-up of 5 years, 90% of patients had no evidence of the disease and most (93,3%) had a good clinical status after surgery; 12 out of 30 patients (40%) had a VP-shunt for hydrocephalus Conclusions GTR is feasible and represents the treatment of choice of SEGAs in TSC. Therapy with m-TOR pathway inhibitors is to be considered in selected patients and especially in recurrences of SEGAs
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- 2019
50. P04.08 The role of SCN1A in glioblastomas and mixed neuronal glial tumors of pediatric age
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Carmen Barba, Annamaria Buccoliero, Davide Mei, Milena Guidi, R Guerrini, Sabrina Giglio, Iacopo Sardi, Cetica, Laura Giunti, De Gregorio, Lorenzo Genitori, and M Censullo
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Mixed Glioma ,Cancer Research ,Pathology ,medicine.medical_specialty ,business.industry ,Central nervous system ,Tissue membrane ,Cancer ,Pediatric age ,medicine.disease ,Poster Presentations ,Epilepsy ,medicine.anatomical_structure ,Oncology ,Glioma ,medicine ,Neurology (clinical) ,business ,Glioblastoma - Abstract
BACKGROUND Low and high grade gliomas, are the most common pediatric central nervous system (CNS) tumors and they show an extremely broad range of clinical behavior. Pediatric glioma is distinct from its adult counterpart with different genetic/epigenetic profile and biological features. Recently, several studies have shown the involvement of voltage-gated Na+ channels (VGSC) in different types of cancer, including gliomas. VGSC are multimeric transmembrane complexes, responsible for membrane depolarization in excitable cells playing an important role also in cell proliferation, migration, apoptosis and differentiation. VGSC are therapeutic targets in cardiovascular and neurological disorders and, in cancers, they could be a novel target for the development of promising anticancer therapy MATERIAL AND METHODS Firstly, we explored the genetic background of 9 pediatric glioblastomas (1–9 pGBMs), through whole-exome sequencing (WES) using HiSeq1000 platform (Illumina) with paired-end approach. On the basis of our results, we extended our study in another group of 16 epileptogenic mixed neuronal-glial tumors of pediatric age, (WHO grade I and II), through an amplicon approach (TSCA) using MiniSeq System platform (Illumina) RESULTS We identified variants in SCN1A gene in 3/9 pGBMs: case 3 had c.5782C>G in tumor and blood; case 5 showed c.2278G>T and two mosaic variants (c.5933C>T, 22% and c.4942C>T, 14%); case 6 showed c.667G>T variant only in tumor, and not in other non tumoral tissues (blood, urine and buccal swab). No variants in SCN1A were identified in a group of 16 pediatric mixed gliomas CONCLUSION In this study, we explore the genetic background of two groups of pediatric neuroepithelial brain tumors, through Next generation sequencing approach. We identified only in pGBMs variants in SCN1A gene that encoded for VGSCs and is involved in a spectrum of early-onset epileptic encephalopathies. None of our mutated patients showed history of epilepsy. Now, it is not clear the significance of these variants in pGBMs but interestingly, these variants are present in pGBM and not in mixed gliomas. Further studies on a big cohort of patients are needed to establish if they could play a role in pGBMs aggressiveness, migration and progression. Moreover, VGSCs could be a pharmacological target in pGBMs treatment
- Published
- 2019
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