Identifying brain tumor patients’ subtypes based on pre-diagnostic history and clinical characteristics: a pilot hierarchical clustering and association analysis

IntroductionCentral nervous system (CNS) tumors are severe health conditions with increasing incidence in the last years. Different biological, environmental and clinical factors are thought to have an important role in their epidemiology, which however remains unclear.ObjectiveThe aim of this pilot study was to identify CNS tumor patients’ subtypes based on this information and to test associations with tumor malignancy.Methods90 patients with suspected diagnosis of CNS tumor were recruited by the Neurosurgery Unit of IRCCS Neuromed. Patients underwent anamnestic and clinical assessment, to ascertain known or suspected risk factors including lifestyle, socioeconomic, clinical and psychometric characteristics. We applied a hierarchical clustering analysis to these exposures to identify potential groups of patients with a similar risk pattern and tested whether these clusters associated with brain tumor malignancy.ResultsOut of 67 patients with a confirmed CNS tumor diagnosis, we identified 28 non-malignant and 39 malignant tumor cases. These subtypes showed significant differences in terms of gender (with men more frequently presenting a diagnosis of cancer; p = 6.0 ×10−3) and yearly household income (with non-malignant tumor patients more frequently earning ≥25k Euros/year; p = 3.4×10−3). Cluster analysis revealed the presence of two clusters of patients: one (N=41) with more professionally active, educated, wealthier and healthier patients, and the other one with mostly retired and less healthy men, with a higher frequency of smokers, personal history of cardiovascular disease and cancer familiarity, a mostly sedentary lifestyle and generally lower income, education and cognitive performance. The former cluster showed a protective association with the malignancy of the disease, with a 74 (14-93) % reduction in the prevalent risk of CNS malignant tumors, compared to the other cluster (p=0.026).DiscussionThese preliminary data suggest that patients’ profiling through unsupervised machine learning approaches may somehow help predicting the risk of being affected by a malignant form. If confirmed by further analyses in larger independent cohorts, these findings may be useful to create potential intelligent ranking systems for treatment priority, overcoming the lack of histopathological information and molecular diagnosis of the tumor, which are typically not available until the time of surgery

Osteoblastoma of the calvaria: Report of two cases diagnosed with MRI and clinical review

The authors describe 2 cases of osteoblastoma of the calvaria and review the clinical features of the 28 cases reported in the world literature. Benign osteoblastoma is a rare tumor that effects young patients, most frequently at temporal level. On the basis of its neuroradiological appearance, it is difficult to formulate a differential diagnosis against other osteoblastic tumors or against osteoid osteoma. In only a few cases MRI findings are reported. In our cases, MRI was more effective than CT scans and radiographs for evaluating the intracranial and intraosseous extension of the tumor. The definitive diagnosis was obtained by combining the histopathological features of the tumor with the clinical and radiological data. The prognosis of this tumor is very good regardless of the type of treatment performed, although both relapse and, more rarely, malignant tumor evolution are possible

Intracranial capillary hemangioma: A description of four cases

Objective: Capillary hemangiomas are benign vascular lesions involving the skin and soft tissues that commonly occur at birth or an early age. Intracranial capillary hemangiomas are extremely rare; only 14 cases have been reported the literature. Case Description: We describe four patients with capillary hemangiomas. In two of these patients the lesions arose from the cavernous sinus. In the third patient, a large capillary hemangioma arising from the middle cranial fossa extended into the infratemporal fossa. The fourth patient had a left hemorrhagic temporoparietal capillary hemangioma. Results: The first two patients underwent a partial resection, followed by radiotherapy. Local tumor control was achieved in both cases, as shown by the follow-up magnetic resonance imaging. In the third patient the lesion was subtotally removed after embolization. Radiotherapy, performed one year after surgery because of recurrence, allowed tumor control. In the fourth patient surgical removal was total and no adjuvant radiotherapy was required after surgery; follow-up magnetic resonance imaging did not show any recurrence at the one-year follow-up. Conclusion: Surgery is an option for symptomatic intracranial capillary hemangiomas. However, because partial removal is associated with a high recurrence rate, capillary hemangiomas that cannot be removed radically should be treated with radiotherapy, which offers the possibility of controlling lesion size and preventing tumor recurrence. © 2012 Elsevier Inc

The Functional Relevance of Diffusion Tensor Imaging in Patients with Degenerative Cervical Myelopathy

(1) Background: In addition to conventional magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) has been investigated as a potential diagnostic and predictive tool for patients with degenerative cervical myelopathy (DCM). In this preliminary study, we evaluated the use of quantitative DTI in the clinical practice as a possible measure to correlate with upper limbs function. (2) Methods: A total of 11 patients were enrolled in this prospective observational study. Fractional anisotropy (FA) values was extracted from DTI data before and after surgery using a GE Signa 1.5 T MRI scanner. The Nine-Hole Peg Test and a digital dynamometer were used to measure dexterity and hand strength, respectively. (3) Results: We found a significant increase of FA values after surgery, in particular below the most compressed level (p = 0.044) as well as an improvement in postoperative dexterity and hand strength. Postoperative FA values moderately correlate with hand dexterity (r = 0.4272, R₂ = 0.0735, p = 0.19 for the right hand; r = 0.2087, R₂ = 0.2265, p = 0.53 for the left hand). (4) Conclusion: FA may be used as a marker of myelopathy and could represent a promising diagnostic value in patients affected by DCM. Surgical decompression can improve the clinical outcome of these patients, especially in terms of the control of finger-hand coordination and dexterity

Loss of EMILIN-1 Enhances Arteriolar Myogenic Tone Through TGF-β (Transforming Growth Factor-β)-Dependent Transactivation of EGFR (Epidermal Growth Factor Receptor) and Is Relevant for Hypertension in Mice and Humans

Objective- EMILIN-1 (elastin microfibrils interface located protein-1) protein inhibits pro-TGF-β (transforming growth factor-β) proteolysis and limits TGF-β bioavailability in vascular extracellular matrix. Emilin1-/- null mice display increased vascular TGF-β signaling and are hypertensive. Because EMILIN-1 is expressed in vessels from embryonic life to adulthood, we aimed at unravelling whether the hypertensive phenotype of Emilin1-/- null mice results from a developmental defect or lack of homeostatic role in the adult. Approach and Results- By using a conditional gene targeting inactivating EMILIN-1 in smooth muscle cells of adult mice, we show that increased blood pressure in mice with selective smooth muscle cell ablation of EMILIN-1 depends on enhanced myogenic tone. Mechanistically, we unveil that higher TGF-β signaling in smooth muscle cells stimulates HB-EGF (heparin-binding epidermal growth factor) expression and subsequent transactivation of EGFR (epidermal growth factor receptor). With increasing intraluminal pressure in resistance arteries, the cross talk established by TGF-β and EGFR signals recruits TRPC6 (TRP [transient receptor potential] classical type 6) and TRPM4 (TRP melastatin type 4) channels, lastly stimulating voltage-dependent calcium channels and potentiating myogenic tone. We found reduced EMILIN-1 and enhanced myogenic tone, dependent on increased TGF-β-EGFR signaling, in resistance arteries from hypertensive patients. Conclusions- Taken together, our findings implicate an unexpected role of the TGF-β-EGFR pathway in hypertension with current translational perspectives

DataSheet_1_Identifying brain tumor patients’ subtypes based on pre-diagnostic history and clinical characteristics: a pilot hierarchical clustering and association analysis.docx

IntroductionCentral nervous system (CNS) tumors are severe health conditions with increasing incidence in the last years. Different biological, environmental and clinical factors are thought to have an important role in their epidemiology, which however remains unclear.ObjectiveThe aim of this pilot study was to identify CNS tumor patients’ subtypes based on this information and to test associations with tumor malignancy.Methods90 patients with suspected diagnosis of CNS tumor were recruited by the Neurosurgery Unit of IRCCS Neuromed. Patients underwent anamnestic and clinical assessment, to ascertain known or suspected risk factors including lifestyle, socioeconomic, clinical and psychometric characteristics. We applied a hierarchical clustering analysis to these exposures to identify potential groups of patients with a similar risk pattern and tested whether these clusters associated with brain tumor malignancy.ResultsOut of 67 patients with a confirmed CNS tumor diagnosis, we identified 28 non-malignant and 39 malignant tumor cases. These subtypes showed significant differences in terms of gender (with men more frequently presenting a diagnosis of cancer; p = 6.0 ×10−3) and yearly household income (with non-malignant tumor patients more frequently earning ≥25k Euros/year; p = 3.4×10−3). Cluster analysis revealed the presence of two clusters of patients: one (N=41) with more professionally active, educated, wealthier and healthier patients, and the other one with mostly retired and less healthy men, with a higher frequency of smokers, personal history of cardiovascular disease and cancer familiarity, a mostly sedentary lifestyle and generally lower income, education and cognitive performance. The former cluster showed a protective association with the malignancy of the disease, with a 74 (14-93) % reduction in the prevalent risk of CNS malignant tumors, compared to the other cluster (p=0.026).DiscussionThese preliminary data suggest that patients’ profiling through unsupervised machine learning approaches may somehow help predicting the risk of being affected by a malignant form. If confirmed by further analyses in larger independent cohorts, these findings may be useful to create potential intelligent ranking systems for treatment priority, overcoming the lack of histopathological information and molecular diagnosis of the tumor, which are typically not available until the time of surgery.</p

Degenerative Lumbar Spine Stenosis Consensus Conference: the Italian Job. Recommendations of the Spinal Section of Italian Society of Neurosurgery

none28In the modern era evidence-based medicine, guidelines and recommendations represent a key-point of daily activity. The Spinal Section of the Italian Society of Neurosurgery introduced some recommendations regarding Degenerative Lumbar Spine Stenosis based on those of the Spine Committee of World Federation of Neurosurgical Societies, revising them on the basis of Italian common practice. Background: In the modern era evidence-based medicine, guidelines and recommendations represent a key-point of daily activity. The Spinal Section of the Italian Society of Neurosurgery introduced some recommendations regarding Degenerative Lumbar Spine Stenosis based on those of the Spine Committee of World Federation of Neurosurgical Societies, revising them on the basis of Italian common practice. Methods: In June 2019, a Committee of 21 spine surgeons met in Rome to validate the recommendations of the WFNS. Furthermore, they decided to review the ones that did not reach a consensus to create Italian Recommendations on Degenerative Lumbar Spine Stenosis. A literature review of the last ten years was performed and the statements were voted using the Delphi method. Results: 41 statements were discussed and 7 statements were voted again to reach a consensus with respect to those of the WFNS. A total of 40 statements reached a consensus, of which 36 reached a positive consensus and 4 a negative consensus, while no consensus was reached in 1 case. Conclusions: Conservative multimodal therapy, tailored on the patient, is a reasonable and effective first option choice for the treatment of LSS patients with tolerable moderate symptoms. Surgical treatment is reserved for symptomatic patients non-responding to conservative treatment or with neurological deficits. The best surgical technique to use depends on personal experience; modern MISS techniques are equivalent to open decompressive surgery with some advantages and higher cost-effectiveness. Fusion surgery and mobility preserving surgery only have a marginal role in the treatment of DLSS without instability.noneCosta, Francesco; Innocenzi, Gualtiero; Guida, Franco; Agrillo, Umberto; Barbagallo, Giuseppe; Bocchetti, Antonio; Bongetta, Daniele; Cappelletto, Barbara; Certo, Francesco; Cimatti, Marco; Cioffi, Valentina; Dobran, Mauro; Domenicucci, Maurizio; Guizzardi, Giancarlo; Guizzardi, Giulia; Landi, Alessandro; Marotta, Nicola; Marzetti, Francesco; Montano, Nicola; Anania, Carla D; Nina, Pierpaolo; Quaglietta, Paolo; Rispoli, Rossella; Somma, Teresa; Squillante, Eleonora; Visocchi, Massimiliano; Vitali, Matteo; Vitiello, VincenzoCosta, Francesco; Innocenzi, Gualtiero; Guida, Franco; Agrillo, Umberto; Barbagallo, Giuseppe; Bocchetti, Antonio; Bongetta, Daniele; Cappelletto, Barbara; Certo, Francesco; Cimatti, Marco; Cioffi, Valentina; Dobran, Mauro; Domenicucci, Maurizio; Guizzardi, Giancarlo; Guizzardi, Giulia; Landi, Alessandro; Marotta, Nicola; Marzetti, Francesco; Montano, Nicola; Anania, Carla D; Nina, Pierpaolo; Quaglietta, Paolo; Rispoli, Rossella; Somma, Teresa; Squillante, Eleonora; Visocchi, Massimiliano; Vitali, Matteo; Vitiello, Vincenz

Unruptured Aneurysms Italian Study (UAIS) background and method

Treatment of unruptured cerebral aneurysms still represents an unsettled question in neurosurgical and neuroradiological communities. Although nowadays the indication for treatment have become relatively clear, indeed uncertainity remains for what concerns the proper treatment modality (surgical or endovascular) in terms of both the risk and the mid and long-term efficacy of the two procedures. The "Unruptured Aneurysms Italian Study" is a cooperative prospective study which aims to delineate the "State of the Art" in a nation based population. It has been designed: 1) to depict the nationwide modality of treatment of Unruptured Aneurysms, 2) to assess in the most objective way the overall treatment-related mortality and morbidity as well as the surgical and endovascular risk in the respective patient populations (it is not a surgical versus endovascular study) and 3) to asses the efficacy of the different procedures in the mid and long term periods. The study started on June 2003 and to June 2006, 637 patients have been enrolled. The study will end when the 1000th patient is enrolled