Publications by authors named "Federico Mussa"

31 Publications

Erratum: Neonatal Cerebellar Hemorrhage and Facial Nerve Palsy: An Unusual Association.

AJP Rep 2020 Jul 25;10(3):e1. Epub 2021 Feb 25.

Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy.

[This corrects the article DOI: 10.1055/s-0040-1715162.][This corrects the article DOI: 10.1055/s-0040-1715162.].
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http://dx.doi.org/10.1055/s-0041-1726119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906837PMC
July 2020

Angiocentric glioma-associated seizures: The possible role of EATT2, pyruvate carboxylase and glutamine synthetase.

Seizure 2021 Mar 16;86:152-154. Epub 2021 Feb 16.

Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Children's Hospital A. Meyer-University of Florence, Italy.

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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http://dx.doi.org/10.1016/j.seizure.2021.02.014DOI Listing
March 2021

Neonatal Cerebellar Hemorrhage and Facial Nerve Palsy: An Unusual Association.

AJP Rep 2020 Jul 2;10(3):e262-265. Epub 2020 Sep 2.

Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy.

Cerebellar hemorrhage is rare in term newborns and is most often seen after traumatic birth. Lifelong sequelae include motor and cognitive impairment. We report the uncommon case of a late preterm infant born by spontaneous delivery who showed right peripheral facial palsy at 24 hours of life. Cranial ultrasound showed lateral ventricles dilatation and a diffuse hyperechoic round lesion in the right cerebellar hemisphere. The computed tomography scan confirmed a hemorrhagic lesion in the right cerebellar hemisphere and in the vermis with midline shift and intraventricular bleeding. Ommaya reservoir was inserted and used for a few days. The facial palsy gradually recovered to a complete remission after 6 weeks. Follow-up examinations at 12 and 18 months evidenced infant's delayed motor function, hyperreflexia, tremors, and speech delay.
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http://dx.doi.org/10.1055/s-0040-1715162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571563PMC
July 2020

Endoscopic sinus and skullbase surgery in pediatric patients during the COVID-19 pandemic.

Br J Neurosurg 2020 May 22:1-2. Epub 2020 May 22.

Department of Neurosurgery, "A. Meyer" Children Hospital of Florence, Florence, Italy.

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http://dx.doi.org/10.1080/02688697.2020.1769554DOI Listing
May 2020

Current Practice in Preoperative Virtual and Physical Simulation in Neurosurgery.

Bioengineering (Basel) 2020 Jan 3;7(1). Epub 2020 Jan 3.

Department of Pediatric Surgery, Meyer Children's Hospital, Viale Pieraccini 24, 50141 Florence, Italy.

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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http://dx.doi.org/10.3390/bioengineering7010007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175342PMC
January 2020

Surgery of complex craniofacial defects: A single-step AM-based methodology.

Comput Methods Programs Biomed 2018 Oct 5;165:225-233. Epub 2018 Sep 5.

Department of Pediatric Surgery, Meyer Children's Hospital, Viale Pieraccini 24, 50141 Florence, Italy.

Background And Objective: The purpose of the present paper is to pave the road to the systematic optimization of complex craniofacial surgical intervention and to validate a design methodology for the virtual surgery and the fabrication of cranium vault custom plates. Recent advances in the field of medical imaging, image processing and additive manufacturing (AM) have led to new insights in several medical applications. The engineered combination of medical actions and 3D processing steps, foster the optimization of the intervention in terms of operative time and number of sessions needed. Complex craniofacial surgical intervention, such as for instance severe hypertelorism accompanied by skull holes, traditionally requires a first surgery to correctly "resize" the patient cranium and a second surgical session to implant a customized 3D printed prosthesis. Between the two surgical interventions, medical imaging needs to be carried out to aid the design the skull plate. Instead, this paper proposes a CAD/AM-based one-in-all design methodology allowing the surgeons to perform, in a single surgical intervention, both skull correction and implantation.

Methods: A strategy envisaging a virtual/mock surgery on a CAD/AM model of the patient cranium so as to plan the surgery and to design the final shape of the cranium plaque is proposed. The procedure relies on patient imaging, 3D geometry reconstruction of the defective skull, virtual planning and mock surgery to determine the hypothetical anatomic 3D model and, finally, to skull plate design and 3D printing.

Results: The methodology has been tested on a complex case study. Results demonstrate the feasibility of the proposed approach and a consistent reduction of time and overall cost of the surgery, not to mention the huge benefits on the patient that is subjected to a single surgical operation.

Conclusions: Despite a number of AM-based methodologies have been proposed for designing cranial implants or to correct orbital hypertelorism, to the best of the authors' knowledge, the present work is the first to simultaneously treat osteotomy and titanium cranium plaque.
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http://dx.doi.org/10.1016/j.cmpb.2018.09.002DOI Listing
October 2018

Endoscopic endonasal skull base surgery in pediatric patients. A single center experience.

J Craniomaxillofac Surg 2018 Dec 24;46(12):2017-2021. Epub 2018 Sep 24.

Anna Meyer Hospital (Azienda Ospedaliero Universitaria Meyer), Neurosurgery Department, Florence, Italy.

Object: At present, a minimally invasive endoscopic endonasal approach is considered an efficient option for lesions affecting the anterior and middle skull base with sellar and parasellar region involvement. In this study we will retrospectively analyze the pediatric patients that we have been treating in the same medical center for the past four years, using an endoscopic approach in the skull base.

Methods: We performed a retrospective chart and imaging review of pediatric patients who underwent endoscopic endonasal skull base surgery (ESBS) at the Meyer Children's Hospital, (Azienda Ospedaliero Universitaria Meyer), in Florence, from January 2012 to July 2016.

Results: Mean age was 12,5 years; 28 (65%) of the 44 patients were females. Skull base lesions were broadly classified as either bony abnormalities (4 cases) or skull base tumors (40 cases). The postoperative clinical follow-up duration ranged from 2 to 36 months. The two more frequently occurring diseases in our study were: craniopharyngioma and pituitary adenoma.

Conclusions: After reviewing the international literature about pediatric endoscopic endonasal approach to skull base, we can affirm that our study is the world's second broadest work for number of records. While compiling this report, we have examined the first 40 consecutive pediatric patients to undergo ESBS at our institute. The appearance of postoperative complications is consistent with other international studies, confirming ESBS being feasible and safe even in the pediatric population.

Level Of Evidence: 4.
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http://dx.doi.org/10.1016/j.jcms.2018.09.013DOI Listing
December 2018

Spinal cord involvement in two children with posterior reversible encephalopathy syndrome.

CNS Oncol 2017 10 6;6(4):287-290. Epub 2017 Oct 6.

Neuro-Oncology Unit, Department of Pediatric Oncology, Anna Meyer Children's University Hospital, Florence 50139, Italy.

Spinal cord involvement (SCI) is a rare feature of posterior reversible encephalopathy syndrome (PRES), especially in children. SCI is generally symptomatic, and may have a different outcome compared with encephalic localization of PRES. We reported about two cases of SCI in pediatric patients with PRES, after multimodal anticancer therapies, including radiotherapy, chemotherapy and targeted agents.
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http://dx.doi.org/10.2217/cns-2017-0003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004885PMC
October 2017

A Diagnostic Pitfall: Atypical Teratoid Rhabdoid Tumor Versus Dedifferentiated/Poorly Differentiated Chordoma: Analysis of a Mono-institutional Series.

Appl Immunohistochem Mol Morphol 2019 02;27(2):147-154

Neurosurgery Unit.

Atypical teratoid/rhabdoid tumor (AT/RT) and dedifferentiated/poorly differentiated chordoma are pediatric tumors with some overlapping morphologic, immunohistochemical, and molecular features. Both these tumors have alterations in the tumor suppressor gene SMARCB1 resulting in loss of expression of the INI-1 protein. On the contrary, dedifferentiated/poorly differentiated chordoma expresses the transcription factor brachyury, whereas AT/RT does not. In this article we have reviewed the clinicopathologic features of a pediatric series of tumors (17 samples from 14 patients) located in the brain or within the axial spine and the base of the skull diagnosed as AT/RTs or as dedifferentiated/poorly differentiated chordomas. On the basis of the INI-1 and brachyury immunohistochemical results we reevaluated the initial diagnoses. Four misdiagnoses were revised. The differential diagnosis between AT/RT and dedifferentiated/poorly differentiated chordoma or on occasion medulloblastoma may be difficult. The use of 2 antibodies, INI-1, and brachyury, may be the key for the right diagnosis.
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http://dx.doi.org/10.1097/PAI.0000000000000554DOI Listing
February 2019

Subependymal giant cell astrocytoma: a lesion with activated mTOR pathway and constant expression of glutamine synthetase.

Clin Neuropathol 2016 Sep-Oct;35(5):295-301

Subependymal giant-cell astrocytoma (SEGA) is a rare tumor associated with tuberous sclerosis complex (TSC). TSC mainly involves the central nervous system (CNS) where SEGA, subependymal nodules, and cortical tubers may be present. First studies suggested the astrocytic nature of SEGA while successive studies demonstrated the mixed glio-neuronal nature. There are similarities between TSC-associated CNS lesions and type IIb focal cortical dysplasia (FCD). In all these pathologies, mammalian target of rapamycin (mTOR) pathway activation has been demonstrated. Recent data evidenced that balloon cells in FCD IIb express glutamine synthetase (GS). GS is involved in the clearance of glutamate. Cells expressing GS might exert an antiepileptic role. We evaluated by immunohistochemistry the glial fibrillary acidic protein (GFAP), neurofilaments (NF), and GS expression and the mTOR status (mTOR and phosphorylated ribosomal protein S6) in 16 SEGAs and 2 cortical tubers. Our purpose was to emphasize the mixed nature of SEGA and to further investigate the similarities between TSC-related CNS lesions (in particular SEGA) and FCD IIb. We confirm the glio-neuronal nature and the common activation of the mTOR pathway in SEGAs. In addition, we report for the first time that these tumors, analogously to FCD IIb, commonly express GS. Notably, the expression of mTOR, phosphorylated ribosomal protein S6, and GS was restricted to gemistocytic-like GFAP-negative cells. GS expression and mTOR pathway activation were also documented in cortical tubers. Further studies are necessary to understand the significance of GS expression in SEGAs as well as in cortical tubers.
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http://dx.doi.org/10.5414/NP300936DOI Listing
February 2017

Development and preliminary assessment of a robotic platform for neuroendoscopy based on a lightweight robot.

Int J Med Robot 2016 Mar 19;12(1):4-17. Epub 2015 Jan 19.

Center for Micro-BioRobotics@SSSA, Istituto Italiano di Tecnologia, Viale Rinaldo Piaggio 34, 56025, Pontedera, Italy.

Background: Ventriculostomy is a widely performed neurosurgical procedure; some risk factors can be mitigated by computer/robot-assisted approaches. Platforms fostering synergistic robot-surgeon integration are pursued, for which lightweight robots with compliant controlled joints must be assessed (because compliance hampers accuracy).

Methods: We developed a platform encompassing, in particular, a lightweight robot and an optical tracker also used to enhance robot accuracy. Based on specifications by neurosurgeons, we designed a neuroendoscope-handling interface and assessed targeting accuracy in a model ventriculostomy where the robot was operated both autonomously and in hands-on (i.e. co-operative) mode.

Results: Targeting errors were systematically below the procedure accuracy threshold (1 mm); the rms targeting errors were 0.51 and 0.54 mm for autonomous and hands-on control, respectively. No significant difference was observed between the considered control modes. Very positive feedback was gathered from neurosurgeons.

Conclusions: Accurate tool targeting under both autonomous and hands-on control was achieved.
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http://dx.doi.org/10.1002/rcs.1638DOI Listing
March 2016

Towards accurate robot-assisted neuroendoscopy using an ergonomic handling interface and a lightweight robot.

Annu Int Conf IEEE Eng Med Biol Soc 2014 ;2014:6876-9

We considered a robot-assisted neuroendoscopy, and we developed a handling interface for linking a clinically-used endoscope to a lightweight robot (tool holder) with 7 DoFs. Such a robot holds potential for soft interaction with the surgeon, yet its intrinsic compliance must be suitably tamed not to lose tool targeting accuracy. Starting from practical specifications by neurosurgeons, we designed, fabricated and preliminarily assessed a compact and ergonomic handling interface. Such an interface permitted to easily insert/retract the tool (the measured force was 2 N), and to accurately hit a predefined target (the mean targeting error was below 0.5 mm, within the accuracy level of the optical tracker used for tool localization and pose). The feedback by neurosurgeons was very positive, thus encouraging further developments.
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http://dx.doi.org/10.1109/EMBC.2014.6945208DOI Listing
September 2015

Pediatric primary anaplastic ganglioglioma: a case report and review of the literature.

Pediatr Neurosurg 2012 21;48(1):35-41. Epub 2012 Aug 21.

Radiation Oncology Unit, Azienda Ospedaliera Universitaria Careggi, Florence, Italy.

Gangliogliomas with anaplastic features are classified as grade III tumors by the World Health Organization. The clinical course and optimal treatment of anaplastic gangliogliomas have not been well understood to date. We report a case of a primary pure anaplastic ganglioglioma in a 14-year-old male treated with surgery and radiotherapy, who is disease-free 6 years after the diagnosis. A review of primary pure anaplastic gangliogliomas in children (between 3 and 21 years of age) is presented. Gross total removal and focal radiotherapy with a total dose of 54 Gy are recommended. The addition of chemotherapy should be evaluated. Prospective studies are needed to identify an appropriate chemotherapy schedule and to define biological factors in order to select those patients with a poor prognosis, who are to be treated with a more aggressive therapy.
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http://dx.doi.org/10.1159/000340067DOI Listing
August 2013

Glioneuronal tumor with neuropil-like islands: clinical, morphologic, immunohistochemical, and molecular features of three pediatric cases.

Pediatr Dev Pathol 2012 Sep-Oct;15(5):352-60. Epub 2012 May 17.

Pathology Unit, Anna Meyer Children's Hospital, Florence, Italy.

Glioneuronal tumors with neuropil-like islands are rare. The 1st reported cases were localized in the cerebral hemispheres of adults, showed homogeneous histopathologic features (infiltrating astrocytic growth and neuropil-like islands rimmed by neuronal cells), and had an unfavorable behavior. We report 3 pediatric cases (1 boy and 2 girls, ages 4, 6, and 8 years, respectively). The boy had a cerebral tumor, and the girls had a spinal tumor. The younger girl also had multiple posterior fossa lesions. The boy and older girl underwent a gross total resection. The younger girl underwent a subtotal resection of the spinal tumor; posterior fossa lesions were not surgically treated. The boy and younger girl are in complete remission at 33 and 24 months, respectively, after surgery and subsequent high-dose chemoradiotherapy. The older girl had a recurrence that was partially resected. Afterward, she started high-dose chemoradiotherapy and had an optimal radiologic response at 4 months follow up. Microscopically, the common denominator was the presence of synaptophysin-positive neuropil-like islands. One tumor showed ependymal features (pseudorosettes and punctate epithelial membrane antigen immunopositivity). Two tumors had 1p deletion. 19q deletion, MGMT gene promoter methylation, EGFR amplifications or polysomy, and EGFR, IDH1, IDH2, and TP53 genes mutation analyses yielded negative results. In conclusion, glioneuronal tumor with neuropil-like islands can affect children, arise in the spinal cord, and show ependymal features in its glial component. A high-dose chemoradiotherapy program is effective.
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http://dx.doi.org/10.2350/12-01-1147-OA.1DOI Listing
April 2013

Primary cerebral myxofibrosarcoma: clinical, morphologic, immunohistochemical, molecular, and ultrastructural study of an infrequent tumor in an extraordinary localization.

J Pediatr Hematol Oncol 2011 Oct;33(7):e279-83

Department of Biomedicine, Careggi Hospital, Florence, Italy.

Herein, we describe an intracerebral primary low-grade myxofibrosarcoma occurring in a 9-year-old boy. The lesion measured 7 cm and occupied the left parieto-occipital region. A gross-total removal of the tumor was performed. Nine months later, radiologic follow-up revealed a local recurrence which was again surgically removed. The patient then underwent radiotherapy and chemotherapy. He was well and disease-free at 6 months follow-up. The tumor was composed of spindle, stellated, and multinucleated cells embedded in a myxoid background. Foci of increased cellularity, pleomorphism, and high mitotic rate were present. The tumor borders were sharply demarcated from the non-neoplastic nervous parenchyma. Immunohistochemical staining showed that the neoplastic cells were vimentine and CD34 positive. Fluorescence in-situ hybridization analyses did not show FUS and EWSR1 gene rearrangements. Primary intracranial myxofibrosarcomas are very rare (to the best of our knowledge, less than 10 published cases in the international literature). We believe each new case should be recorded to produce a better clinical, pathologic, molecular, prognostic, and therapeutic characterization of this lesion.
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http://dx.doi.org/10.1097/MPH.0b013e318211834eDOI Listing
October 2011

Pediatric rhabdoid meningioma: a morphological, immunohistochemical, ultrastructural and molecular case study.

Neuropathology 2011 Feb;31(1):59-65

Department of Biomedicine, Careggi Hospital, Florence, Italy.

Rhabdoid meningioma is an uncommon meningioma variant categorized as WHO grade III. The majority of cases occur in adulthood. Herein, we describe a right fronto-temporal rhabdoid meningioma affecting a 3-year-old boy. The lesion measured approximately 4 cm in diameter and incorporated the ipsilateral middle cerebral artery. Sub-total surgical excision of the mass was performed. Histologically, the tumor was mainly composed of globoid plump cells with inclusion-like eosinophilic cytoplasm, peripheral nuclei, prominent nucleoli and occasional intra-nuclear cytoplasmic pseudo-inclusion. The cells appeared in many areas loosely arranged and focally disclosed a papillary architecture. At immunohistochemistry, the tumor cells were EMA, vimentin, HHF35, PgR, INI-1 and p53 positive. The proliferative index (Mib-1) was 15% in the most positive areas. Ultrastructurally, tumoral cells showed an abundant cytoplasm, which was filled with numerous intermediate filaments. Desmosomal junctions were seen. RT-PCR revealed the presence of NF2 gene expression. Molecular study did not indicate alterations of the INI-1 gene, whereas it showed the presence of Pro72Arg in exon 4 at heterozygous state in the TP53 gene. Morphologic features along with immunohistochemical, ultrastructural and molecular results were consistent with the diagnosis of rhabdoid meningioma. The patient was treated with chemotherapy. The lesion remained stable after 33 months of follow-up. Rhabdoid meningiomas rarely occur in children. Owing to its rarity, each new case should be recorded to produce a better clinical, pathological, molecular, prognostic and therapeutic characterization of this lesion.
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http://dx.doi.org/10.1111/j.1440-1789.2010.01113.xDOI Listing
February 2011

Surgical management of congenital median perisellar transsphenoidal encephaloceles with an extracranial approach: a series of 6 cases.

Neurosurgery 2009 Dec;65(6):1140-5; discussion 1145-6

Department of Pediatric Neurosurgery, Anna Meyer Children's Hospital, Florence, Italy

Objective: Median perisellar congenital transsphenoidal encephalocele (CTE) is a rare entity associated with multiple endocrine, visual, and respiratory deficits. The most likely causative factor for these pathological alterations is distension of neural structures (hypothalamic-pituitary system, optic pathway), resulting in protrusion of the dural sac through a sphenoid bone defect into the pharynx. The continuity with the extracranial space can be associated with an increased risk of tearing of the sac, with consequent cerebrospinal fluid leakage and subsequent increase in the risk of infection. We retrospectively reviewed the surgical treatment of CTE in our hospital using either an extracranial transoral or transnasal approach.

Methods: We retrospectively reviewed our database. Between July 1994 and June 2005, CTE we identified 6 patients. Five of them were treated by a surgical intervention. The first patient was treated via a transcranial approach but had a relapse of the prolapse 11 years later. The relapse was treated with an extracranial transpalatal approach. Four patients were treated with an extracranial surgical approach: an extracranial transoral approach was performed in 2 cases, and an extracranial transnasal approach was used in the other 2 cases. Surgery was not performed in 1 patient because the parents refused to consent to the procedure.

Results: Preoperative symptoms remained stable or improved in all of the patients after the surgical procedure and worsened in the patient who did not have a surgical intervention. Two patients experienced a palatal dehiscence. No mortality was recorded in this series of patients.

Conclusion: The surgical treatment of CTE is indicated to stop the progression or improve symptoms related to this disease entity. If approached correctly, the extracranial approach is a safe procedure with subsequent low morbidity.
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http://dx.doi.org/10.1227/01.NEU.0000351780.23357.F5DOI Listing
December 2009

Monotherapy with thalidomide for treatment of spinal cord hemangioblastomas in a patient with von Hippel-Lindau disease.

Pediatr Blood Cancer 2009 Sep;53(3):464-7

Department of Pediatric Hematology-Oncology, A.U.O. Anna Meyer Children's Hospital, Florence, Italy.

Von Hippel-Lindau (VHL) disease is a cancer-prone syndrome characterized by abnormalities in vascular proliferation and the development of both the visceral and CNS tumors. Complications from hemangioblastoma are among the principal causes of death from this syndrome. Antiangiogenic therapy has been used with different modalities in patients suffering from such complications. Here, we describe an adolescent with VHL complicated by progressive, multifocal spinal hemangioblastomas. Treatment with single-agent thalidomide over the course of 3 years was associated with an unexpected stabilization of the disease. The antiangiogenic effect of thalidomide may be associated with the control of progressive hemangioblastoma.
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http://dx.doi.org/10.1002/pbc.22065DOI Listing
September 2009

Pediatric sinonasal neuroendocrine carcinoma after treatment of retinoblastoma.

Hum Pathol 2009 May 20;40(5):750-5. Epub 2009 Jan 20.

Department of Human Pathology and Oncology, University of Florence, 50134 Florence, Italy.

Patients who survive retinoblastoma are at risk for developing additional malignant neoplasms, including tumors of the sinonasal tract. We report 2 cases of secondary sinonasal malignancy arising in pediatric patients previously treated for retinoblastoma, with features of neuroendocrine carcinoma. Both lesions were characterized by a proliferation of round to oval cells arranged in solid sheets, trabeculae, and nests, diffusely infiltrating nasal mucosa and bone tissue. Immunohistochemically, they were diffusely positive for epithelial markers, as well as for neuroendocrine markers and for TP53 and retinoblastoma gene products. TP53 gene analysis showed the presence of a missense mutation P72R (CCC/CGC) and a single nucleotide polymorphism P36P (CCG/CCA) in exon 4 in 1 case. Literature review revealed 5 previously reported cases, all showing primitive undifferentiated morphology with variable expression of neural and epithelial markers. These tumors represent a peculiar subset of undifferentiated sinonasal neoplasms with extremely aggressive clinical behavior.
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http://dx.doi.org/10.1016/j.humpath.2008.09.018DOI Listing
May 2009

Surgical treatment of central nervous system malformations.

Handb Clin Neurol 2008 ;87:569-90

Department of Neurosurgery, Ospedale Pediatrico Meyer, Via Luca Giordano 13, Florence, Italy.

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http://dx.doi.org/10.1016/S0072-9752(07)87031-XDOI Listing
December 2010

Your diagnosis? A 12-year-old girl with latent tuberculosis presenting with nausea, vomiting and increasing frontal headache.

Eur J Pediatr 2009 Feb 13;168(2):245-6. Epub 2008 Sep 13.

Department of Paediatrics, University of Florence, Anna Meyer Children's Hospital, via Luca Giordano 13, 50132 Florence, Italy.

A 12-year-old girl with latent Mycobacterium tuberculosis infection and currently receiving prophylaxis with isoniazid presented with nausea, vomiting and increasing frontal headache. Toxicity to the anti-tuberculosis drug was suspected, but her symptoms persisted after isoniazid withdrawal. A computed tomography (CT) scan showed a brain mass to be present.
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http://dx.doi.org/10.1007/s00431-008-0814-yDOI Listing
February 2009

Subependymal giant cell astrocytoma (SEGA): Is it an astrocytoma? Morphological, immunohistochemical and ultrastructural study.

Neuropathology 2009 Feb 17;29(1):25-30. Epub 2008 Jun 17.

Department of Human Pathology and Oncology, University of Florence, Italy.

Subependymal giant-cell astrocytoma (SEGA) is a rare intra-ventricular low-grade tumor which frequently occurs as a manifestation of tuberous sclerosis complex. The histogenesis of SEGA is controversial and its astrocytic nature has been doubted. First studies suggested the astrocytic nature of SEGA while several recent reports demonstrate its glio-neuronal nature. In spite of this, in the recently revised WHO classification of the CNS tumors, SEGA has been still included in the group of astrocytomas. We studied nine tuberous sclerosis complex-associated SEGAs. Patients were 1-18 years old. Eight patients (89%) had a solitary lesion located in the lateral ventricle close to of the head of the caudate nucleus, the remaining patient (11%) had two tumors, one located close to the head of the left caudate nucleus and the other in the central part of the right lateral ventricle. Histologically, tumors were composed of three types of cells: spindle, gemistocytic and ganglion-like. Four tumors (44%) had a prominent vascularization and three (33%) showed an angiocentric pattern. Calcifications were observed in six cases (66%). By immunohistochemistry, the majority of the tumors were GFAP- (9; 100%), neurofilament- (8, 89%), neuron-specific enolase- (9, 100%), and synaptophysin- (8; 89%) positive. Ultrastructural studies were performed on four cases. In all four there were glial cell processes filled with intermediate filaments. In one case dense core putative neurosecretory granules were appreciable. Our results emphasize the glio-neuronal nature of SEGA. We suggest moving it into the group of mixed glio-neuronal tumors under the denomination of subependymal giant cell tumor.
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http://dx.doi.org/10.1111/j.1440-1789.2008.00934.xDOI Listing
February 2009

Intracavitary chemotherapy (Gliadel) and oral low-dose etoposide for recurrent anaplastic ependymoma.

Oncol Rep 2008 May;19(5):1219-23

Neuro-surgery Units, Department of Neurosurgery, University of Florence Medical School, The A. Meyer Children's Hospital, Florence 50132, Italy.

Anaplastic ependymoma is associated with a higher incidence of tumor recurrence and its prognosis still remains unsatisfactory. Consolidated therapy for ependymoma includes surgery followed by focal radiotherapy when resection is incomplete. In the case of relapse treatment, options are limited especially for patients who have already received radiotherapy. We sought to establish the feasibility of administering low-dose oral etoposide (50 mg/m(2)/day for 21 days) in combination with the implantation of intracavitary carmustine (BCNU) wafers (Gliadel) at the gross total resection for achieving synergistic treatment in three children affected by recurrent anaplastic ependymoma. All patients had Karnofsky performance scale (KPS) scores >80%. The therapy was tolerated safely and well in all patients without any post-surgery complications. After BCNU wafer implantation, all patients achieved radiological and clinical stabilization for an average period of 3 months. Two patients relapsed after 4 months as shown in brain MRIs. The other patient went to progression two months after the Gliadel implantation. This multimodal approach was not effective for the treatment of refractory anaplastic ependymoma and further studies are required in order to define the role of the combination of multidrug systemic chemotherapy with BCNU wafer implantation in children with high-risk brain tumors.
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May 2008

Hox-D genes expression in pediatric low-grade gliomas: real-time-PCR study.

Cell Mol Neurobiol 2009 Feb 11;29(1):1-6. Epub 2008 Apr 11.

Department of Human Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 85, 50134, Florence, Italy,

HOX genes encode transcription factors, which play a key role in morphogenesis and cell differentiation during embryogenesis. Several observations indicate that a deregulated expression of these genes may result in tumor development and progression. Actually, several HOX genes are aberrantly expressed in many tumors and cell lines derived from them. Little is known about the expression of HOX genes in brain tumors. In the present work, we study the relative expression of HOX-D genes (D1, D3, D4, D8, D9, D10, D11, D12, D13) with real-time polymerase chain reaction in a group of 14 pediatric low-grade gliomas. We compare the HOX-D expression level of the 14 tumors with the average expression level of six non-neoplastic human brain tissues. HOX-D1 and HOX-D12 resulted over-expressed in neoplastic samples with respect to non-neoplastic brain parenchyma. Conversely, HOX-D3 was expressed at a lower level in gliomas with respect to non-neoplastic brain. HOX-D4, HOX-D11, and HOX-D13 were never expressed. HOX-D8, HOX-D9, and HOX-D10 were exceptionally expressed in non-neoplastic samples and irregularly expressed in tumors. The observation that all but three HOX-D genes studied are expressed with different pattern in neoplastic and non-neoplastic brain tissue may support the hypothesis that HOX-D genes play a role in the pathogenesis of pediatric low-grade gliomas.
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http://dx.doi.org/10.1007/s10571-008-9282-1DOI Listing
February 2009

Maximizing results in craniofacial surgery with bioresorbable fixation devices.

J Craniofac Surg 2007 Jul;18(4):926-30

Wake Forest University Baptist Medical Center, Plastic and Reconstructive Surgery Department, Winston-Salem, North Carolina, USA.

The resorbable plating system allows the infant's skull to grow once the system is resorbed, thus not inhibiting the necessary developmental growth seen with the titanium system. Despite marked improvements in long-term outcomes, there are still technical points that can be followed to maximize outcome while reducing and possibly eliminating minor complications such as plate palpability and visibility through the skin as well as skin breakdown over the plate. A retrospective electronic chart review was performed on the pediatric patient population who underwent craniofacial surgery with the use of resorbable fixation devices by the senior author (LG). Fifty-two patients underwent surgical correction for craniosynostosis with resorbable material (Craniosorb, Lactosorb, or Biosorb PDX). This series included patients with brachycephaly (17), anterior plagiocephaly (unilateral coronal synostosis; 16), trigonocephaly (11), multisuture craniosynostosis (7), and Cohen's craniotelencephalic dysplasia (1). The mean age at the time of the operation was 8 months and the mean follow up was 17 months. Eight patients experienced complications related to the resorbable material. Seven of the eight had complete resolution of symptoms after conservative treatment and one patient had complete resolution of the skin infection after plate removal. The purpose of this study was to evaluate the risks and complications with the use of resorbable material to establish guidelines for avoidance of surgical pitfalls that lead to increased risk of morbidity with the use of this material, particularly as it relates to plate visibility under the skin, plate palpability, skin breakdown, and skin infections over the plating system.
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http://dx.doi.org/10.1097/scs.0b013e3180a771e9DOI Listing
July 2007

Focal cortical dysplasia type 1b as a cause of severe epilepsy with multiple independent spike foci.

Brain Dev 2008 Jan 20;30(1):53-8. Epub 2007 Jun 20.

Department of Pediatrics, Section of Pediatric Neurology, Policlinico Le Scotte, University of Siena, Siena, Italy.

To investigate the clinical picture, the neurophysiological pattern, and neuropathological features of a young woman with severe drug-resistant epilepsy of unknown cause. We used the patient's clinical records from the age of 2 to 20years including neurophysiological patterns recorded via both scalp and cortex electrodes and results of studies conducted on the brain neuropathological specimen. The patient, with severe mental/psychomotor retardation, suffered from severe epilepsy from an early age, characterized by daily seizures of multiple types (atypical absences, tonic, and complex partial seizures), high frequency, and intractability. The neurophysiological pattern indicated multiple independent spike foci (SE-MISF). When she was 16, a vagal nerve stimulator was implanted without success. Neither neuroimaging (brain MRI and ictal SPECT) nor surface EEGs identified unique loci of seizure onset, establishing her as a candidate for a complete callosotomy. When the patient was 19, before the callosotomy, invasive EEG (i.e., electrocorticography) using just a few electrodes in different lobes showed the presence of a distinctive pattern. The surgical specimen, taken very close to one of the activity sites, showed architectural abnormalities and neurons that were giant or immature but not dysmorphic, indicative of focal cortical dysplasia (FCD) type 1b. Twelve months after the callosotomy, according to the Engel score, the patient exhibited a large improvement in quality of life, without permanent complications from the interhemispheric disconnection. (1) Hidden FCD type 1b could represent a missing diagnosis in patients with SE-MISF in the absence of other causes for their seizures. (2) Complete callosotomy can be efficacious in patients with SE-MISF with hidden FCD type 1b.
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http://dx.doi.org/10.1016/j.braindev.2007.05.010DOI Listing
January 2008

Complications and pitfalls of neuroendoscopic surgery in children.

J Neurosurg 2006 Sep;105(3 Suppl):187-93

Department of Pediatric Neurosurgery, "Regina Margherita" Children's Hospital, Turin, Italy.

Object: Neuroendoscopic surgery is being used as an alternative to traditional shunt surgery and craniotomy in the management of hydrocephalus and intracranial fluid-filled cavities. In this study, the authors evaluated the incidence and type of complications occurring after neuroendoscopic procedures that were performed in a consecutive series of pediatric patients at a single institution to determine the effectiveness of neuroendoscopy in such patients.

Methods: Four hundred ninety-five neuroendoscopic procedures were consecutively performed in 450 pediatric patients at one institution over a 10-year period. Charts were retrospectively reviewed. A complication was defined as follows: 1) any postoperative neurological deficit that was not observed before surgery; 2) any event occurring during surgery that resulted in the procedure being aborted; or 3) any adverse event occurring within 7 days postsurgery that resulted in a modification of the normal postoperative care. However, headache, vomiting, and fever without cerebrospinal fluid (CSF) pleocytosis were not considered complications. Complications were observed in 40 (8.1%) of 495 procedures. Two patients had two complications. One patient died of diffuse brain edema following endoscopic biopsy sampling of a basal ganglia tumor (mortality rate 0.2%). Other complications observed were abandonment of the procedure in eight cases, CSF leakage in 11 (with associated wound infection in one), intraventricular hemorrhage in six (with external drainage needed in four), intraparenchymal hemorrhage in three, subdural collection in eight (with subdural-peritoneal shunt placement needed in seven), transient oculomotor palsy in two, and transient hemiparesis in one.

Conclusions: Many complications can be avoided by determining the correct diagnosis and using suitable techniques and instruments. Most complications can be managed conservatively and do not produce long-term morbidity. Complex procedures in most patients and simple procedures in patients with preoperative risk factors carry the highest hazard. Every attempt should be made to optimize the surgical technique. The most serious and potentially the most lethal complication remains arterial bleeding from injury to the basilar artery complex.
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http://dx.doi.org/10.3171/ped.2006.105.3.187DOI Listing
September 2006

Papillary glioneuronal tumor radiologically mimicking a cavernous hemangioma with hemorrhagic onset.

Neuropathology 2006 Jun;26(3):206-11

Department of Human Pathology and Oncology, University of Florence, Florence, Italy.

Papillary glioneuronal tumor is a recently identified low-grade brain neoplasm classified as variant of ganglioglioma. Its salient morphological characteristics are the presence of pseudopapillary structures composed of blood vessels, often hyalinized, lined by uniform small astrocytes and a proliferation of neurocytic cells, eventually admixed with ganglioid and ganglion cells. We present a case of papillary glioneuronal tumor occurring in a 15-year-old female with an unusual hemorrhagic onset. The clinical, morphological and immunohistochemical features are discussed and the published literature is reviewed. This article proposes that papillary glioneuronal tumor should be included in the differential diagnosis of patients with tumoral related brain hemorrhage.
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http://dx.doi.org/10.1111/j.1440-1789.2006.00674.xDOI Listing
June 2006