Publications by authors named "Giorgio Carrabba"

60 Publications

Does COVID-19 Affect Survival and Functional Outcome in Emergency and Urgent Neurosurgical Procedures? A Single-Center Prospective Experience During the Pandemic.

World Neurosurg 2021 Jun 22. Epub 2021 Jun 22.

Department of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Medical-Surgical Physiopathology and Transplantation, University of Milan, Milan, Italy; "Aldo Ravelli" Research Center, Milan, Italy.

Objective: To assess organizational and technical difficulties of neurosurgical procedures during the coronavirus disease 2019 (COVID-19) pandemic and their possible impact on survival and functional outcome and to evaluate virological exposure risk of medical personnel.

Methods: Data for all urgent surgical procedures performed in the COVID-19 operating room were prospectively collected. Preoperative and postoperative variables included demographics, pathology, Karnofsky performance status (KPS) and neurological status at admission, type and duration of surgical procedures, length of stay, postoperative KPS and functional outcome comparison, and destination at discharge. We defined 5 classes of pathologies (traumatic, oncological, vascular, infection, hydrocephalus) and 4 surgical categories (burr hole, craniotomy, cerebrospinal fluid shunting, spine surgery). Postoperative SARS-CoV-2 infection was checked in all the operators.

Results: We identified 11 traumatic cases (44%), 4 infections (16%), 6 vascular events (24%), 2 hydrocephalus conditions (8%), and 2 oncological cases (8%). Surgical procedures included 11 burr holes (44%), 7 craniotomies (28%), 6 cerebrospinal fluid shunts (24%), and 1 spine surgery (4%). Mean patient age was 57.8 years. The most frequent clinical presentation was coma (44 cases). Mean KPS score at admission was 20 ± 10, mean surgery duration was 85 ± 63 minutes, and mean length of stay was 27 ± 12 days. Mean KPS score at discharge was 35 ± 25. Outcome comparison showed improvement in 16 patients. Four patients died. Mean follow-up was 6 ± 3 months. None of the operators developed postoperative SARS-CoV-2 infection.

Conclusions: Standardized protocols are mandatory to guarantee a high standard of care for emergency and urgent surgeries during the COVID-19 pandemic. Personal protective equipment affects maneuverability, dexterity, and duration of interventions without affecting survival and functional outcome.
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http://dx.doi.org/10.1016/j.wneu.2021.06.071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216838PMC
June 2021

The "Parachute" Technique for the Endoscopic Repair of High-Flow Anterior Skull-Base CSF Leaks.

World Neurosurg 2021 Jul 8;151:e880-e887. Epub 2021 May 8.

Department of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; "Aldo Ravelli" Research Center, Milan, Italy; Department of Medical-Surgical Physiopathology and Transplantation, University of Milan, Milan, Italy.

Objective: This study aims to assess the feasibility and reliability of our endoscopic trans-nasal technique for the repair of cribriform and sellar high-flow cerebrospinal fluid (CSF) leaks.

Methods: A comparison between patients suffering from high-flow rhinorrhea and treated through a free grafting endoscopic technique or the "parachute" technique, our nasal packing proposal, was performed.

Results: Thirty-three patients were included. The mean age was 52 years (range: 36-68 years). The etiology of the CSF leaks was iatrogenic in 16 cases (48.5%), traumatic in 5 cases (15.2%), spontaneous in 11 cases (33.3%), and related to anterior skull base tumors in 1 case (3%). The bone defect affected the sphenoidal sinus in 20 cases (60.6%), the cribriform plate of the ethmoid in 10 cases (30.3%), and both the sphenoid and ethmoid in 3 cases (9.1%). The mean size of bone defects was 8.5 ± 3.9 mm. The median follow-up was 28 (64) months. A CSF leak recurrence occurred in no cases treated with the parachute technique and in 3 cases that underwent conventional endoscopic treatments. The CSF leak recurrences were associated with 2 iatrogenic and 1 post-traumatic fistula. All the CSF leak recurrences underwent the parachute technique, not showing second recurrences.

Conclusions: Our results suggest that the parachute technique is simple, safe, and effective. We recommend it as an alternative treatment to vascular flaps for the treatment of high-flow and recurrent fistulas.
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http://dx.doi.org/10.1016/j.wneu.2021.05.006DOI Listing
July 2021

Plasma levels of extracellular vesicles and the risk of post-operative pulmonary embolism in patients with primary brain tumors: a prospective study.

J Thromb Thrombolysis 2021 Jul 10;52(1):224-231. Epub 2021 Apr 10.

A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Via Pace 9, 20122, Milan, Italy.

Primary brain tumors are associated with an increased risk of pulmonary embolism (PE), particularly in the early post-operative period. The pathophysiological mechanisms of PE are poorly understood. This study aims to describe prospectively extracellular vesicles (EVs) levels and investigate whether or not their variations allow to identify patients at increased risk of post-operative PE. Consecutive meningioma or glioma patients candidate to tumor resection were included in the study if a pulmonary perfusion scan (Q-scan) performed before surgery ruled out PE. EVs derived from platelets (CD41) or endothelial cells (CD144), tissue factor-bearing EVs (CD142) and their procoagulant subtype (annexin V) were analyzed by flow cytometry before surgery (T0), within 24 h (T1), two (T2) and seven days (T7) after surgery. Q-scan was repeated at T2. Ninety-three patients with meningioma, 59 with glioma and 76 healthy controls were included in the study. CD142 and annexin V/CD142 EVs were increased at T0 in meningioma and glioma patients compared to healthy controls. Twenty-nine meningioma (32%) and 16 glioma patients (27%) developed PE at T2. EVs levels were similar in meningioma patients with or without PE, whereas annexin V and annexin V/CD142 EVs were significantly higher at T1 and T2 in glioma patients with PE than in those without. Procoagulant EVs, particularly annexin V/CD142, increase after surgery and are more prevalent in glioma patients who developed PE after surgery than in those who did not.
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http://dx.doi.org/10.1007/s11239-021-02441-3DOI Listing
July 2021

Insular lobe surgery and cognitive impairment in gliomas operated with intraoperative neurophysiological monitoring.

Acta Neurochir (Wien) 2021 05 24;163(5):1279-1289. Epub 2020 Nov 24.

Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, Padiglione Monteggia, 20122, Milan, Italy.

Background: For a long time, surgery of insular gliomas was considered at high risk for postoperative cognitive deficits, but recent studies highlighted the feasibility of the surgical approach. The aims of our study were to investigate the presence of language impairment before and after surgery and the relationship between language impairment and tumor volume preoperatively and extent of resection (EOR) 3 months after surgery.

Methods: Thirty-five patients with insular gliomas underwent an extensive language assessment before and few days after surgery, and after 3 months. Intraoperative neurophysiological monitoring (IOM) and brain mapping with direct electrical stimulation (DES) were used in all the cases; 8 patients underwent awake craniotomy. Statistical analysis was performed on the language tests administered.

Results: Patients with pure left insular lesion showed language impairment before and after surgery. Overall, patients with a left lesion showed a drop of performance after surgery followed by a partial recovery. Moreover, when the tumor involved the insula and adjacent networks, we observed a more severe deficit. No correlations were found between tumor volume, EOR, and language impairment.

Conclusions: Left insular lobe is an important hub in language networks; its involvement determines pre- and postsurgical deficits, together with the involvement of white matter connections. Tumor volume and EOR are not risk factors per se directly related to language functioning. Surgery of insular gliomas is possible with a pre- and intraoperative extensive study of the patient with IOM and awake surgery, and encouraged by the trend of cognitive recovery highlighted.
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http://dx.doi.org/10.1007/s00701-020-04643-9DOI Listing
May 2021

Pre- and Post-Zygotic TP53 De Novo Mutations in SHH-Medulloblastoma.

Cancers (Basel) 2020 Sep 3;12(9). Epub 2020 Sep 3.

Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy.

Li-Fraumeni syndrome (LFS) is an autosomal dominant disorder caused by mutations in the gene, predisposing to a wide spectrum of early-onset cancers, including brain tumors. In medulloblastoma patients, the role of TP53 has been extensively investigated, though the prevalence of de novo mutations has not been addressed. We characterized TP53 mutations in a monocentric cohort of consecutive Sonic Hedgehog (SHH)-activated medulloblastoma patients. Germline testing was offered based on tumor p53 immunostaining positivity. Among 24 patients, three (12.5%) showed tumor p53 overexpression, of whom two consented to undergo germline testing and resulted as carriers of TP53 mutations. In the first case, family history was uneventful and the mutation was not found in either of the parents. The second patient, with a family history suggestive of LFS, unexpectedly resulted as a carrier of the mosaic mutation c.742=/C>T p.(Arg248=/Trp). The allele frequency was 26% in normal tissues and 42-77% in tumor specimens. Loss of heterozygosity (LOH) in the tumor was also confirmed. Notably, the mosaic case has been in complete remission for more than one year, while the first patient, as most TP53-mutated medulloblastoma cases from other cohorts, showed a severe and rapidly progressive disease. Our study reported the first TP53 mosaic mutation in medulloblastoma patients and confirmed the importance of germline testing in p53 overexpressed SHH-medulloblastoma, regardless of family history.
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http://dx.doi.org/10.3390/cancers12092503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564492PMC
September 2020

Personalized and translational approach for malignant brain tumors in the era of precision medicine: the strategic contribution of an experienced neurosurgery laboratory in a modern neurosurgery and neuro-oncology department.

J Neurol Sci 2020 Oct 6;417:117083. Epub 2020 Aug 6.

Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Aldo Ravelli" Research Center, Milan, Italy; Clinical Pathology Unit, Istituto di Medicina Aerospaziale "A. Moosso", Aeronautica Militare, Milan, Italy.

Personalized medicine (PM) aims to optimize patient management, taking into account the individual traits of each patient. The main purpose of PM is to obtain the best response, improving health care and lowering costs. Extending traditional approaches, PM introduces novel patient-specific paradigms from diagnosis to treatment, with greater precision. In neuro-oncology, the concept of PM is well established. Indeed, every neurosurgical intervention for brain tumors has always been highly personalized. In recent years, PM has been introduced in neuro-oncology also to design and prescribe specific therapies for the patient and the patient's tumor. The huge advances in basic and translational research in the fields of genetics, molecular and cellular biology, transcriptomics, proteomics, and metabolomics have led to the introduction of PM into clinical practice. The identification of a patient's individual variation map may allow to design selected therapeutic protocols that ensure successful outcomes and minimize harmful side effects. Thus, clinicians can switch from the "one-size-fits-all" approach to PM, ensuring better patient care and high safety margin. Here, we review emerging trends and the current literature about the development of PM in neuro-oncology, considering the positive impact of innovative advanced researches conducted by a neurosurgical laboratory.
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http://dx.doi.org/10.1016/j.jns.2020.117083DOI Listing
October 2020

Reduced-dose craniospinal irradiation is feasible for standard-risk adult medulloblastoma patients.

J Neurooncol 2020 Jul 21;148(3):619-628. Epub 2020 Jun 21.

Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University, Rome, Italy.

Introduction: Medulloblastoma is the most common malignant brain tumor in children, but accounts for only 1% of brain cancers in adults. For standard-risk pediatric medulloblastoma, current therapy includes craniospinal irradiation (CSI) at reduced doses (23.4 Gy) associated with chemotherapy. Whereas most same-stage adult patients are still given CSI at 36 Gy, with or without chemotherapy, we report here on our use of reduced-dose CSI associated with chemotherapy for older patients.

Methods: We gathered non-metastatic patients over 18 years old (median age 28 years, range 18-48) with minimal or no residual disease after surgery, no negative histological subtypes, treated between 1996-2018 at the Centre Léon Bérard (Lyon) and the INT (Milano). A series of 54 children with similar tumors treated in Milano was used for comparison.

Results: Forty-four adults were considered (median follow-up 101 months): 36 had 23.4 Gy of CSI, and 8 had 30.6 Gy, plus a boost to the posterior fossa/tumor bed; 43 had chemotherapy as all 54 children, who had a median 83-month follow-up. The PFS and OS were 82.2 ± 6.1% and 89 ± 5.2% at 5 years, and 78.5 ± 6.9% and 75.2 ± 7.8% at ten, not significantly different from those of the children. CSI doses higher than 23.4 Gy did not influence PFS. Female adult patients tended to have a better outcome than males.

Conclusion: The results obtained in our combined series are comparable with, or even better than those obtained after high CSI doses, underscoring the need to reconsider this treatment in adults.
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http://dx.doi.org/10.1007/s11060-020-03564-yDOI Listing
July 2020

The suprasellar volume of nonfunctioning pituitary adenomas: a useful tool for predicting visual field deficits.

Pituitary 2020 Oct;23(5):552-557

Department of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via Francesco Sforza, 20122, Milan, Italy.

Purpose: The aim of the present study is to assess the predictive value of the suprasellar volume (SSV) of nonfunctioning pituitary adenomas (NFPAs) for visual field (VF) impairment in order to guide clinical decision-making and improve neurosurgical management.

Methods: Two independent samples of patients with NFPAs (exploratory population N = 50, testing population N = 98) were included in the present study. In the first phase, we determined the optimal cut-off value of the SSV correlating with VF deficits in the exploratory population. In the second phase, we then studied the accuracy of identified cut-off in predicting a VF deficit in the testing population.

Results: In the exploratory population, the optimal cut-off value of the SSV to determine the presence of a VF deficit was 1.5 mL. Sensitivity and specificity of the cut-off were 81.3 and 100%, respectively. The positive predictive value (PPV) and the negative predictive value (NPV) were 100 and 75%, respectively. When we checked the identified cut-off score on the testing population, we found a sensitivity of 71% and a specificity of 100%. The PPV and NPV were 100 and 59.2%, respectively. In six cases with VF defects and SSV inferior to 1.5 mL, the displacement of optic chiasm was in superior position.

Conclusion: The SSV may represent an accurate method in routinely clinical practice for predicting VF deficit in patients affected by NFPA.
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http://dx.doi.org/10.1007/s11102-020-01060-0DOI Listing
October 2020

microRNAs and Markers of Neutrophil Activation as Predictors of Early Incidental Post-Surgical Pulmonary Embolism in Patients with Intracranial Tumors.

Cancers (Basel) 2020 Jun 11;12(6). Epub 2020 Jun 11.

Haemostasis, Thrombosis, Atherosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain.

Venous thromboembolism (VTE) is a common complication of cancer that severely increases morbidity and mortality. Patients with intracranial tumors are more likely to develop VTE than patients with cancers at other sites. Conversely, limited tools exist to identify patients with high thrombotic risk. Upon activation, neutrophils release their content through different mechanisms triggering thrombosis. We explored the ability of microRNAs (miRNAs) and plasma markers of neutrophil activation measured before surgery to predict the risk of early post-surgical pulmonary embolism (PE) in glioma and meningioma patients. We recruited and prospectively followed 50 patients with glioma and 50 with meningioma, 34% of whom in each group developed an early objectively-diagnosed post-surgical PE. We measured miRNA expression and neutrophil markers (cell-free DNA, nucleosomes, calprotectin and myeloperoxidase) before surgery. In glioma patients, we adjusted and validated a predictive model for post-surgical PE with 6 miRNAs: miR-363-3p, miR-93-3p, miR-22-5p, miR-451a, miR-222-3p and miR-140-3p (AUC = 0.78; 95% Confidence Interval (CI) [0.63, 0.94]) and another with cfDNA and myeloperoxidase as predictors (AUC = 0.71; 95%CI [0.52, 0.90]). Furthermore, we combined both types of markers and obtained a model with myeloperoxidase and miR-140-3p as predictors (AUC = 0.79; 95%CI [0.64, 0.94]). In meningioma patients we fitted and validated a predictive model with 6 miRNAs: miR-29a-3p, miR-660-5p, miR-331-3p, miR-126-5p, miR-23a-3p and miR-23b-3p (AUC = 0.69; 95%CI [0.52, 0.87]). All our models outperformed the Khorana score. This is the first study that analyzes the capability of plasma miRNAs and neutrophil activation markers to predict early post-surgical PE in glioma and meningioma patients. The estimation of the thrombotic risk before surgery may promote a tailored thromboprophylaxis in a selected group of high-risk patients, in order to minimize the incidence of PE and avoid bleedings.
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http://dx.doi.org/10.3390/cancers12061536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353032PMC
June 2020

Letter to the Editor: Impact of COVID-19 Outbreak on Acute Low Back Pain.

World Neurosurg 2020 07 29;139:749. Epub 2020 May 29.

Department of Neurosurgery, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

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http://dx.doi.org/10.1016/j.wneu.2020.05.218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256499PMC
July 2020

Neurosurgery in an infant with COVID-19.

Lancet 2020 05 22;395(10234):e76. Epub 2020 Apr 22.

Neurosurgery Department, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano 20143, Italy.

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http://dx.doi.org/10.1016/S0140-6736(20)30927-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176389PMC
May 2020

Retrospective analysis of the clinical and radiological features of 94 consecutive DIPGs patients to investigate the factors determining the development of hydrocephalus and its impact on clinical status and survival.

Childs Nerv Syst 2020 11 28;36(11):2701-2705. Epub 2020 Mar 28.

Pediatric Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Purpose: There is no consensus in the literature about the impact of hydrocephalus on clinical course and overall survival of diffuse intrinsic pontine gliomas (DIPG) patients as well as about its specific treatment. Authors reviewed a series of DIPG patients to investigate factors related to the onset of hydrocephalus, its treatment, and its impact on clinical course and prognosis.

Methods: A retrospective observational study was performed enrolling pediatric patients affected by DIPG from 2008 to 2018. Clinical and radiological charts were reviewed to find patients' demographic, pathologic and radiologic features in hydrocephalic and non-hydrocephalic patients. In the hydrocephalus cohort, treatment strategy and its effectiveness and complications were analyzed.

Results: Ninety-four pediatric patients were enrolled in the study. Patients who developed hydrocephalus showed significantly lesser maximum axial tumor areas than patients without hydrocephalus (respectively 6.5 cm vs 16.45 cm, p < 0.005). Hydrocephalus developed in 33 patients (35%) with an onset interval of 5.24 ± 1.21 months (range 3.2-7.3). The majority of hydrocephalic patients (28 cases, 90%) were treated by ventriculoperitoneal shunt, the remaining 3 patients being treated by endoscopic third ventriculostomy. Mean overall survival was 16.6 months ± 20 months without significative difference between the groups.

Conclusion: The onset of hydrocephalus occurs in the first moths of the disease story and found a negative correlation with tumor maximal axial diameter. Early treatment of hydrocephalus presents a very low complications rate with satisfying clinical outcome, as it allows the patients to continue the neurooncological therapies being a part of the treatment armamentarium instead of a palliative solution.
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http://dx.doi.org/10.1007/s00381-020-04589-4DOI Listing
November 2020

Long-term follow-up of neuropsychological functions in patients with high grade gliomas: can cognitive status predict patient's outcome after surgery?

Acta Neurochir (Wien) 2020 04 28;162(4):803-812. Epub 2020 Jan 28.

Unit of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35 (Padiglione Monteggia), 20122, Milan, Italy.

Background: Patients affected by a high-grade glioma (HGG) have a poor prognosis with a median survival of 12-16 months. Such poor prognosis affects the perception of the remaining life by patients and the neuropsychological status can strongly affect every-day functioning of these patients. Monitoring changes of neuropsychological functioning (NPF) overtime may provide better clinical information and optimize the neuro-oncological management. The aims of our work were (1) to investigate the feasibility of a complex neuropsychological battery in HGG patients before and during follow-up after surgery; (2) to study the neuropsychological profile of patients affected by HGGs and their relation with the disease status (relapse/death) across time after surgery.

Methods: One hundred two patients who received surgery for HGG between 2011 and 2017 were studied. All clinical data were prospectively recorded. NPF was assessed during the neuro-oncological follow-up through the Milano-Bicocca Battery (MIBIB). Statistical analysis was performed on the neuropsychological results of the tests administered.

Results: First, MIBIB proved to be suitable for patients with HGG tumors before and after surgery, and during long-term follow-up; it also showed a cluster structure representative of the principal cognitive domains. Second, we found a steep decline in the neuropsychological profile before death and/or tumor relapse for the 52% of the neuropsychological tests administered.

Conclusion: Complex neuropsychological batteries can be administered to HGG patients before and during follow-up after surgery. There is a correlation between neuropsychological deterioration and tumor relapse and/or death, which may reflect a progressive damage to cognitive functions due to tumor infiltration and progression.
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http://dx.doi.org/10.1007/s00701-020-04230-yDOI Listing
April 2020

Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology.

Cells 2020 01 25;9(2). Epub 2020 Jan 25.

Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.

Circulating platelets (PLTs) are able to affect glioblastoma (GBM) microenvironment by supplying oncopromoter and pro-angiogenic factors. Among these mediators, sphingosine-1-phophate (S1P) has emerged as a potent bioactive lipid enhancing cell proliferation and survival. Here, we investigated the effect of "tumor education", characterizing PLTs from GBM patients in terms of activation state, protein content, and pro-angiogenic potential. PLTs from healthy donors (HD-PLTs) and GBM patients (GBM-PLTs) were collected, activated, and analyzed by flow cytometry, immunofluorescence, and Western blotting. To assess the pro-angiogenic contribution of GBM-PLTs, a functional cord formation assay was performed on GBM endothelial cells (GECs) with PLT-releasate. GBM-PLTs expressed higher positivity for P-selectin compared to HD-PLTs, both in basal conditions and after stimulation with adenosine triphosphate (ADP) and thrombin receptor activating peptide (TRAP). PLTs showed higher expression of VEGFR-1, VEGFR-2, VWF, S1P, S1PR1, SphK1, and SPNS. Interestingly, increased concentrations of VEGF and its receptors VEGFR1 and VEGFR2, VWF, and S1P were found in GBM-PLT-releasate with respect to HD-PLTs. Finally, GBM-PLT-releasate showed a pro-angiogenic effect on GECs, increasing the vascular network's complexity. Overall, our results demonstrated the contribution of PLTs to GBM angiogenesis and aggressiveness, advancing the potential of an anti-PLT therapy and the usefulness of PLT cargo as predictive and monitoring biomarkers.
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http://dx.doi.org/10.3390/cells9020294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072723PMC
January 2020

Cushing's disease: a prospective case-control study of health-related quality of life and cognitive status before and after surgery.

J Neurosurg 2019 Nov 15:1-11. Epub 2019 Nov 15.

2Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan.

Objective: Some studies have highlighted psychological and neuropsychological difficulties and a potential reduction in health-related quality of life (HRQOL) in patients with pituitary tumors, despite hormone deficits or excess. To the authors' knowledge, this study is the first prospective longitudinal case-control study with the aim of simultaneously testing whether HRQOL and psychiatric and neuropsychological disabilities are related to neural dysfunction due to hypercortisolism per se, or tumor mass and/or surgery in patients with Cushing's disease (CD). The authors evaluated a homogeneous cohort of patients with CD and nonfunctioning pituitary adenomas (NFPAs) before and after neurosurgery and compared these patients with healthy controls.

Methods: Twenty patients (10 with NFPA and 10 with CD) were evaluated using 3 validated questionnaires (SF-36, Beck Depression Inventory-II [BDI-II], and Minnesota Multiphasic Personality Inventory-II [MMPI-II]) to assess HRQOL and psychological status preoperatively and 12 months after neurosurgery. Neuropsychological tests were assessed preoperatively, 3-7 days postoperatively, and 12 months postoperatively. Twenty healthy matched controls were recruited.

Results: Preoperatively, the NFPA and CD subgroups had worse HRQOL scores than controls on the basis of SF-36 scores, although the NFPA subgroup experienced significant recovery 12 months postoperatively. Preoperatively, CD patients had depressive symptoms according to the BDI-II and MMPI-II that persisted 12 months postoperatively, together with social introversion and hypochondriasis; NFPA patients were similar to controls except for hypochondriasis scores that were clinically significant at all timepoints. Preoperatively and 3-7 days postoperatively, both subgroups showed significant neuropsychological disabilities compared with controls, but only the CD subgroup did not completely recover over time.

Conclusions: HRQOL and neuropsychological impairments were observed in all patients at early timepoints, independent of hypercortisolism, tumor mass, and successful surgery. Over time, CD patients showed persistent changes in HRQOL, in particular in social activities. In this light, CD seems to have a strong impact on HRQOL and to be associated with more psychological and neuropsychological comorbidities than NFPA.
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http://dx.doi.org/10.3171/2019.8.JNS19930DOI Listing
November 2019

Minimally invasive fetal surgery for myelomeningocele: preliminary report from a single center.

Neurosurg Focus 2019 10;47(4):E12

3Obstetrics-Fetal Surgery.

Objective: Recent trials have shown the safety and benefits of fetoscopic treatment of myelomeningocele (MMC). The authors' aim was to report their preliminary results of prenatal fetoscopic treatment of MMC using a biocellulose patch, focusing on neurological outcomes, fetal and maternal complications, neonatal CSF leakage, postnatal hydrocephalus, and radiological outcomes.

Methods: Preoperative assessment included clinical examination, ultrasound imaging, and MRI of the fetus. Patients underwent purely fetoscopic in utero MMC repair, followed by postoperative in utero and postnatal MRI. All participants received multidisciplinary follow-up.

Results: Five pregnant women carrying fetuses affected by MMC signed informed consent for the fetoscopic treatment of the defect. The mean MMC size was 30.4 mm (range 19-49 mm). Defect locations were L1 (2 cases), L5 (2 cases), and L4 (1 case). Hindbrain herniation and ventriculomegaly were documented in all cases. The mean gestational age at surgery was 28.2 weeks (range 27.8-28.8 weeks). Fetoscopic repair was performed in all cases. The mean gestational age at delivery was 33.9 weeks (range 29.3-37.4 weeks). After surgery, reversal of hindbrain herniation was documented in all cases. Three newborns developed signs of hydrocephalus requiring CSF diversion. Neurological outcomes in terms of motor level were favorable in all cases, but a premature newborn died due to CSF infection and sepsis.

Conclusions: The authors' preliminary results suggest that fetoscopic treatment of MMC is feasible, reproducible, and safe for mothers and their babies. Neurological outcomes were favorable and similar to those in the available literature. As known, prematurity was the greatest complication.
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http://dx.doi.org/10.3171/2019.8.FOCUS19438DOI Listing
October 2019

Medulloblastoma and central nervous system germ cell tumors in adults: is pediatric experience applicable?

Childs Nerv Syst 2019 12 14;35(12):2279-2287. Epub 2019 Aug 14.

SC Pediatria, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, 20133, Milan, Italy.

Medulloblastoma and central nervous system (CNS) germ cell tumors are very rare in adults, while they account for 25% and 5% of brain tumors in children, respectively (Pastore et al. Eur J Cancer 42:2064-208, 2006). Pediatric experiences, mostly from randomized and controlled clinical trials, have led to different tailored treatments, based on various risk factors, including histology, and extent of disease. For medulloblastoma, biological features have recently emerged that enable therapies to be scaled down in some cases, or pursued more aggressively in the event of chromosomal and/or genetic alterations (Massimino et al. Crit Rev Oncol Hematol 105:35-51, 2016). Such refinements are still impossible for adult patients due to the lack of similar clinical trials that might provide the same or a different understanding regarding patients' prognosis, long-term survival, quality of life, and acute and late toxicities. This review aims to contribute to the debate on the treatment of adults with these two diseases and promote the creation of broad-based, national and international trials to advance our knowledge in this area and to share the skills between pediatric and adult oncologists as adolescent and young adults (AYA) brain tumor national boards are currently requiring.
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http://dx.doi.org/10.1007/s00381-019-04340-8DOI Listing
December 2019

Therapeutic effect of Anakinra in the relapsing chronic phase of febrile infection-related epilepsy syndrome.

Epilepsia Open 2019 Jun 27;4(2):344-350. Epub 2019 Mar 27.

Department of Neuroscience Istituto di Ricerche Farmacologiche Mario Negri IRCCS Milano Italy.

Febrile infection-related epilepsy syndrome (FIRES) is a severe epileptic encephalopathy with presumed inflammatory origin and lacking effective treatments. Anakinra is the human recombinant interleukin 1 receptor antagonist clinically used in autoinflammatory or autoimmune conditions. We report a case of FIRES for which the spatial and temporal match between electroencephalography (EEG) and magnetic resonance imaging (MRI) focal alterations provides support for the detrimental synergic interplay between seizures and inflammation that may evolve to permanent focal lesions and progressive brain atrophy in weeks to months. Brain biopsy showed aspects of chronic neuroinflammation with scarce parenchymal lymphocytes. We report the novel evidence that anakinra reduces the relapse of highly recurrent refractory seizures at 1.5 years after FIRES onset. Our evidence, together with previously reported therapeutic effects of anakinra administered since the first days of disease onset, support the hypothesis that interleukin 1β and inflammation-related factors play a crucial role in seizure recurrence in both the acute and chronic stages of the disease.
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http://dx.doi.org/10.1002/epi4.12317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546072PMC
June 2019

Cerebrospinal Fluid Level of Aquaporin4: A New Window on Glymphatic System Involvement in Neurodegenerative Disease?

J Alzheimers Dis 2019 ;69(3):663-669

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, UOSD Neurologia - Malattie Neurodegenerative, Milan, Italy.

Aquaporin4 (AQP4) is a water channel protein located at astrocyte foot processes that plays a role in glymphatic system, a highly organized fluid transport pathway which seems to be involved in Alzheimer's disease (AD) and normal pressure hydrocephalus (NPH) pathophysiology. Cerebrospinal fluid (CSF) AQP4 levels were determined in 11 patients with AD, 10 patients with NPH, and 9 controls. We found significantly reduced AQP4 in AD patients, a trend in reduction in NPH patients, and a correlation between AQP4 and amyloid-β CSF levels. This study indicates the potential role of AQP4 and glymphatic system in neurodegenerative diseases pathophysiology.
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http://dx.doi.org/10.3233/JAD-190119DOI Listing
September 2020

Pseudotumour cerebri associated with mycoplasma pneumoniae infection and treatment with levofloxacin: a case report.

BMC Pediatr 2019 01 5;19(1). Epub 2019 Jan 5.

Pediatric Highly Intensive Care Unit, Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico, and a Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.

Background: Idiopathic intracranial hypertension (IIH), also known as pseudotumour cerebri syndrome (PTCS), is characterized by the presence of signs and symptoms of raised intracranial pressure without evidence of any intracranial structural cause and with normal cerebrospinal fluid microscopy and biochemistry. Obesity, various systemic diseases and endocrine conditions, and a number of medications are known to be risk factors for PTCS. The medications commonly associated with PTCS are amiodarone, antibiotics, corticosteroids, cyclosporine, growth hormone, oral contraceptives, vitamin A analogues, lithium, phenytoin, NSAIDs, leuprolide acetate, and some neuroleptic drugs. In relation to antibiotics, quinolones may cause intracranial hypertension, and most reported cases of quinolone-induced intracranial hypertension were associated with nalidixic acid, ciprofloxacin, ofloxacin, or pefloxacin. Literature reports of levofloxacin-induced PTCS are rare. Some authors recently hypothesized that Mycoplasma pneumoniae may trigger PTCS.

Case Presentation: We report on a 14-year-old overweight White Italian boy who suffered headache, diplopia, and severe bilateral papilloedema after a Mycoplasma pneumoniae infection, exacerbated on levofloxacin intake. A spontaneous improvement in headache and a reduction in diplopia was seen during hospitalisation. Oral acetazolamide therapy led to the regression of papilloedema in about five months. No permanent eye damage has been observed in our patient to date.

Conclusions: PTCS pathophysiology may be multifactorial and its specific features and severity may be a consequence of both constitutional and acquired factors interacting synergistically. It may be useful for paediatricians to know that some antibiotics may have the potential to precipitate PTCS in patients who already have an increased CSF pressure due to a transitory imbalanced CSF circulation caused by infections such as Mycoplasma pneumoniae, with headache being the first and most sensitive, but also the least specific, symptom.
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http://dx.doi.org/10.1186/s12887-018-1371-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320575PMC
January 2019

Optic Radiation Diffusion Tensor Imaging Tractography: An Alternative and Simple Technique for the Accurate Detection of Meyer's Loop.

World Neurosurg 2018 Sep 30;117:e42-e56. Epub 2018 May 30.

Unit of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Background: The optic radiation (OR) is a white matter bundle with a very complex anatomy. Its anterior component bends sharply around the tip of the temporal horn, forming the Meyer's loop (ML), the sparing of which during surgery is crucial to preserve visual function. Defining its exact anatomy and accurately identifying its position remain challenging, even with diffusion tensor imaging (DTI) tractography and the most refined tracking procedure. We have developed an alternative tracking technique to detect the ML position.

Methods: We performed DTI studies in 26 patients undergoing resection of a temporo-parieto-occipital lesion. We then reconstructed the ORs of each patient using 2 techniques (the first developed by our team, the other taken from the literature), using the same tracking software and parameters. We evaluated the accuracy of each technique measuring 3 distances that define the ML position. We created 5 data groups and compared the 2 techniques. Finally, we compared our results with the results from 8 anatomic dissection studies and other tractographic studies.

Results: Our findings show that our technique allows a more accurate definition of the ML position. We found a statistically significant (P < 0.05) difference for all the distances between the 2 techniques; our results resemble those obtained in dissection studies. Our technique is also easy to perform and repeatable.

Conclusions: Our tracking technique may be of marked interest for the evaluation and anatomic definition of the ML position, particularly for neurosurgeons approaching the anterior temporal region.
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http://dx.doi.org/10.1016/j.wneu.2018.05.131DOI Listing
September 2018

Constructional Apraxia in Older Patients with Brain Tumors: Considerations with an Up-To-Date Review of the Literature.

World Neurosurg 2018 Jun 31;114:e1130-e1137. Epub 2018 Mar 31.

Division of Neurosurgery, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. Electronic address:

Background: Constructional apraxia (CA) is a neuropsychological impairment of either basic perceptual and motor abilities or executive functions, in the absence of any kind of motor or perceptual deficit. Considering patients with focal brain tumors, CA is common in left or right parietal and parieto-occipital lesions. In neuropsychology, the Rey-Osterrieth Complex Figure Test (ROCFT; or parallel forms) is commonly used for the assessment of CA. This study stems from a clinical observation of a difficulty with CA tests for the majority of older neurosurgical patients without occipitoparietal lesions.

Methods: Patients were tested at 3 points: before surgery, 3 months after surgery, and 12 months after surgery. Thirty patients (15 meningiomas and 15 glioblastomas) were studied retrospectively.

Results: Older patients with focal brain lesions, regardless of the nature of the tumor, performed poorly at CA tests. More than 50% of patients obtained pathologic results at all 3 times considered.

Conclusions: Our findings suggest that as CA complex tests involve multiple domains, poor results in copy task may reflect a global cognitive deficit of older patients with tumors, without a specific constructional praxis deficit. CA complex tests (such as the ROCFT) do not give significant informations about visuo-constructional abilities.
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http://dx.doi.org/10.1016/j.wneu.2018.03.159DOI Listing
June 2018

Rathke's cleft cyst associated with pituitary granulomatosis with polyangiitis: An unusual combination of hypothalamus-pituitary region pathologies.

Radiol Case Rep 2018 Feb 31;13(1):233-236. Epub 2017 Oct 31.

Department of Neurosurgery, Fondazione IRCCS "Ca' Granda" Ospedale Maggiore Policlinico, Milan, Italy.

The authors present an unusual case of a patient suffering from visual deficit due to pituitary granulomatosis with polyangiitis (GPA) associated with Rathke's cleft cyst (RCC). The patient was referred to our Neurosurgery Department presenting right eye amaurosis, third cranial nerve palsy, and left temporal hemianopsia. Magnetic resonance imaging documented a sellar or suprasellar lesion with solid and cystic components. The dura mater of the skull base was also strongly enhanced. The patient underwent surgery. Histologic examination revealed RCC associated with pituitary GPA. To our knowledge, this is the first reported case of concomitant pituitary GPA and RCC. Pituitary involvement in GPA is rare, usually diagnosed in hormonal dysfunctions. The patient in case first presented optic chiasm compression, probably due to inflammation of both the pituitary gland and the previously asymptomatic RCC. We focus on the symptoms that led us to diagnose GPA pituitary involvement and on the peculiar and unusual Magnetic resonance imaging of the case presented.
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http://dx.doi.org/10.1016/j.radcr.2017.09.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853151PMC
February 2018

Risk of post-operative venous thromboembolism in patients with meningioma.

J Neurooncol 2018 Jun 2;138(2):401-406. Epub 2018 Mar 2.

Neurosurgery, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Via F. Sforza, 35, 20122, Milan, Italy.

The surgical resection of meningiomas can be complicated by venous thromboembolism (VTE) in the post-operative period, but the exact incidence of this event is not known. Aim of this study was to assess the occurrence of VTE in patients operated for meningioma who underwent a post-operative clinical and objective screening for VTE. Patients undergoing meningioma resection between 2000 and 2010 who accepted to be investigated for VTE in the post-operative period were included in the study. The screening included daily clinical assessment, pulmonary perfusion scintigraphy (Q-SCAN) on day 2 and venous compression ultrasonography (CUS) of the lower limbs within day 7. The univariate and multivariate statistical analysis of risk factors for VTE included sex, age, presence of comorbidities, pre- and post-operative Karnofsky Performance scale (KPS), post-operative neurological worsening and post-operative walking ability. Two-hundred and seventy-five patients were included in the study. VTE was diagnosed in 82 patients (29.8%). Univariate analysis revealed that age ≥ 65 years, cardiovascular comorbidities, pre- and post-operative KPS < 80/100, post-operative neurological worsening and impaired post-operative walking ability were significantly associated with VTE. Multivariate analysis confirmed only age ≥ 65 years (p = 0.011) and post-operative KPS < 80/100 (p = 0.002) as independent risk factors for VTE. Patients operated for meningioma have a 30% risk of VTE. Age ≥ 65 years and post-operative KPS < 80 were independent risk factors for VTE.
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http://dx.doi.org/10.1007/s11060-018-2810-zDOI Listing
June 2018

Surgery in elderly patients with intracranial meningioma: neuropsychological functioning during a long term follow-up.

J Neurooncol 2018 May 12;137(3):611-619. Epub 2018 Jan 12.

Division of Neurosurgery, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza, 35, 20122, Milan, Italy.

Surgical treatment of elderly patients with meningioma is has proved to be safe, especially when patients are selected using dedicated surgical scores. These scores take into account tumor size, edema, location and patient's co-morbidities. Neuropsychological functioning (NPF) of this kind of patients has been poorly studied in literature and it is not taken into account by these scores. Aim of our study was to describe the long-term outcome in terms of NPF of elderly patients undergoing surgery. Patients older than 70 years of age affected by intracranial meningioma and selected with the Clinical-Radiological Grading Score were included in our study. Neuropsychological testing was performed using a dedicated battery of tests before surgery, 3 and 12 months after surgery. Clinical, neurological and radiological outcomes were studied as well. Forty-one patients with a median age of 74 years were included in this study. Preoperatively only 1/41 patients showed a normal NPF with all tests scoring normally. Four out of 39 patients showed a complete neuropsychological recovery after 3 months; while 10/37 patients had a complete recovery after 12 months. NPF showed a trend of progressive improvement after surgery. Our study is the first experience reported in literature describing a long term follow-up in elderly patients after surgery for intracranial meningioma. In our series, surgery determined an improvement of NPF over time; especially with a low complication rate related to the selection of patients obtained through the CRGS. Further studies need to be performed in order to understand how brain edema, tumor size, volume and tumor location affect NPF in both short and long term.
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http://dx.doi.org/10.1007/s11060-018-2754-3DOI Listing
May 2018

External ventricular drain causes brain tissue damage: an imaging study.

Acta Neurochir (Wien) 2017 10 8;159(10):1981-1989. Epub 2017 Aug 8.

Neuroscience Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122, Milan, Italy.

Background: An external ventricular drain (EVD) is used to measure intracranial pressure (ICP) and to drain cerebrospinal fluid (CSF). The procedure is generally safe, but parenchymal sequelae are reported as a possible side effect, with variable incidence. We investigated the mechanical sequelae of EVD insertion and their clinical significance in acute brain-injured patients, with a special focus on hemorrhagic lesions.

Methods: Mechanical sequelae of EVD insertion were detected in patients by computed tomography (CT) and magnetic resonance imaging (MRI), performed for clinical purposes.

Results: In 155 patients we studied the brain tissue surrounding the EVD by CT scan (all patients) and MRI (16 patients); 53 patients were studied at three time points (day 1-2, day 3-10, >10 days after EVD placement) to document the lesion time course. Small hemorrhages, with a hyperdense core surrounded by a hypodense area, were identified by CT scan in 33 patients. The initial average (hyper- + hypodense) lesion volume was 8.16 ml, increasing up to 15 ml by >10 days after EVD insertion. These lesions were not accompanied by neurologic deterioration or ICP elevation. History of arterial hypertension, coagulation abnormalities and multiple EVD insertions were significantly associated with hemorrhages. In 122 non-hemorrhagic patients, we detected very small hypodense areas (average volume 0.38 ml) surrounding the catheter. At later times these hypodensities slightly increased. MRI studies in 16 patients identified both intra- and extracellular edema around the catheters. The extracellular component increased with time.

Conclusion: EVD insertion, even when there are no clinically important complications, causes a tissue reaction with minimal bleedings and small areas of brain edema.
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http://dx.doi.org/10.1007/s00701-017-3291-0DOI Listing
October 2017

Analysis of factors influencing the access to concomitant chemo-radiotherapy in elderly patients with high grade gliomas: role of MMSE, age and tumor volume.

J Neurooncol 2017 Sep 6;134(2):377-385. Epub 2017 Jul 6.

Division of Neurosurgery, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy.

High grade gliomas (HGG) are tumors with a rapidly progressive course and the standard of care consists of surgery and chemo-radiotherapy. Elderly patients with HGG usually have a worse prognosis due to their comorbidities and difficulties in accessing or completing adjuvant treatments. The purpose of our study was to assess the influence of pre-operative factors (MMSE, age, sex, KPS, tumor volume) on the post-operative access to chemo-radiotherapy in the elderly population. In addition, the influence of the access to adjuvant therapies on overall survival (OS) was assessed. We retrospectively reviewed our consecutive case series of 117 elderly patients (≥65 years) with HGG treated in our Institution. All the clinical records regarding age, sex, tumor location, MMSE, KPS, access to adjuvant treatments and OS were analyzed. 72 males and 45 females with a median age of 71 years were analyzed. Adjuvant therapies were considered; concomitant chemo-radiotherapy with standard radiotherapy or hypofractionated radiation regimen. 84 patients had access to adjuvant therapies. Access to therapies was associated with a median age of 71(range 66-80) years, a median MMSE of 26(range 5-30), and a median tumor volume of 24 cm(range 1-140). The median OS was 13 months for patients who had access to adjuvant therapies and 5 months for patients who did not. In the elderly patients with HGG, the MMSE, age and tumor volume were predictive of post-surgery access to adjuvant treatments. OS was significantly longer in elderly patients with HGG who had access to post-surgery chemo-radiotherapy.
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http://dx.doi.org/10.1007/s11060-017-2537-2DOI Listing
September 2017

Globus pallidus internus deep brain stimulation in PINK-1 related Parkinson's disease: A case report.

Parkinsonism Relat Disord 2017 05 20;38:93-94. Epub 2017 Feb 20.

Neuropathophysiology Unit, Fondazione IRCCS Ospedale Maggiore Policlinico, Milan, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.parkreldis.2017.02.018DOI Listing
May 2017

Is Complex Sphenoidal Sinus Anatomy a Contraindication to a Transsphenoidal Approach for Resection of Sellar Lesions? Case Series and Review of the Literature.

World Neurosurg 2017 Apr 5;100:173-179. Epub 2017 Jan 5.

Unit of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Background: The transsphenoidal approach is considered the gold standard for resection of pituitary adenomas and other sellar region lesions. This approach is guided by a few fundamental anatomic landmarks that conduct the surgeon toward the sellar floor. Some anatomic structures may vary a lot (e.g., intrasphenoidal septa, intercarotid distance) and may be difficult to identify. Pneumatization and conformation of the sphenoidal sinus (SS) plays a key role in accessing the floor of the sella and other skull base structures. A poorly pneumatized SS may be a relative contraindication to the transsphenoidal approach. We analyzed outcome and complications in transsphenoidal surgery for sellar lesions with a difficult SS.

Methods: We analyzed 243 consecutive patients who underwent a transsphenoidal approach for sellar lesions. Patients with poor pneumatization of the SS were included. Neurosurgical and endocrinologic outcomes were reported.

Results: Successful treatment using a transsphenoidal approach with neuronavigation and Doppler ultrasound was achieved in 15 patients with a low degree of pneumatization of the SS. A pituitary adenoma was present in 13 of 15 patients. Endocrinologic and neurosurgical outcomes were similar to patients with normal pneumatization of the SS, showing a cure of disease in 6 of 9 patients with functioning adenomas and an improvement of symptoms in cases of nonfunctioning adenomas.

Conclusions: Patients with a poorly pneumatized SS can be treated safely with a transsphenoidal approach using image guidance techniques to avoid major neurovascular complications.
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http://dx.doi.org/10.1016/j.wneu.2016.12.123DOI Listing
April 2017

Risk of Infection After Local Field Potential Recording from Externalized Deep Brain Stimulation Leads in Parkinson's Disease.

World Neurosurg 2017 Jan 28;97:64-69. Epub 2016 Sep 28.

Clinical Center for Neurostimulation, Neurotechnology, and Movement Disorders, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; III Department of Health Sciences, University of Milan & Ospedale San Paolo, Milan, Italy. Electronic address:

Objective: Adaptive deep brain stimulation (aDBS) controlled by local field potentials (LFPs) is considered a promising treatment for advanced Parkinson's disease (PD). The clinical research investigating aDBS functioning is performed using external deep brain stimulation (DBS) systems that require LFP recording through the temporary externalization of DBS leads. Although research examining LFP was first undertaken more than 20 years ago, only a few studies concern lead externalization and LFP recording safety. In the present retrospective study, we assessed the risk of infection related to these procedures.

Methods: A total of 105 patients with PD who underwent DBS surgery and lead externalization at our hospital from 2002 to 2014 were included in the present study. The medical records were used to collect clinical data and information concerning surgical site infections. We assessed the infection incidence in our cohort and the risk of infection related to the LFP recording procedure.

Results: The incidence of infections in patients who underwent lead externalization was 2.8%, which was consistent with the postoperative infectious risk reported in the literature (Wilcoxon signed rank test; P > 0.05). Moreover, the LFP recording procedure did not significantly increase the infection risk (LFP recordings vs. no LFP recordings: 2.5% vs. 4.2%; Fisher exact test; P > 0.05).

Conclusions: DBS lead externalization and LFP recording are safe and do not increase the postoperative infection risk in patients with PD who undergo DBS surgery. Our retrospective study supported further clinical research in the field of LFP-based aDBS.
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http://dx.doi.org/10.1016/j.wneu.2016.09.069DOI Listing
January 2017
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