Towards a common language in neurosurgical outcome evaluation: the NEON (NEurosurgical Outcome Network) proposal.

BACKGROUND: The aim of this study was to achieve a consensus on the minimum set of outcome measures and predictors to be used in the neurosurgical practice and on the timing of outcome assessment. METHODS: A consensus building approach was employed. All neurosurgical departments in Lombardy (Italy) were invited to participate by the Carlo Besta Neurologic Institute IRCCS Foundation. Three workshops were organized during which a multidisciplinary group called Neurosurgical Outcome Network (NEON) was created and the methodology to select outcome measures, predictors, and timing of outcome assessment was established. Eight working groups were created for the different neurosurgical diseases (neuro-oncological, skull base, vascular, traumatic, spinal, peripheral nervous system, malformation, functional) and 8 workshops were organized to identify the outcome measures and predictors specific for each of the neurosurgical diseases based on the experts' clinical practice and the existing literature. RESULTS: A total of 20 neurosurgical departments participated in this study. Specific outcome measures, predictors and the timing of outcome assessment were identified for each of the 8 neurosurgical diseases. Moreover, a list of variables common to all pathologies were identified by the NEON group as further data to be collected. CONCLUSIONS: A consensus on the minimum set of outcome measures and predictors and the timing of outcome assessments for 8 neurosurgical diseases was achieved by a group of neurosurgeons of the Lombardy region, called NEON. These sets could be used in future studies for a more homogeneous data collection and as a starting point to reach further agreement also at national and international level.

Posterior fossa syndrome in a population of children and young adults with medulloblastoma: a retrospective, multicenter Italian study on incidence and pathophysiology in a histologically homogeneous and consecutive series of 136 patients.

INTRODUCTION: Posterior fossa syndrome (PFS) is a set of debilitating complications that can occur after surgery for posterior fossa tumors. This study aimed to assess the preoperative radiological and surgical risk factors for the onset of PFS in a histologically homogeneous population of children with medulloblastoma and compare it to a similar population of young adults. METHODS: Included patients underwent posterior fossa surgery for medulloblastoma at 11 Italian neurosurgical wards (2003-2019) and were referred to Fondazione IRCCS Istituto Nazionale dei Tumori in Milan (INT) for postoperative treatments. We collected patients' pre- and post-operative clinical, surgical and radiological data from the INT charts. To compare the distribution of variables, we used the Mann-Whitney and Fisher tests for continuous and categorical variables, respectively. RESULTS: 136 patients (109 children and 27 young adults) were included in the study. Among children, 29 (27%) developed PFS, and all of them had tumors at midline site with invasion of the fourth ventricle. Radiological evidence of involvement of the right superior (39% versus 12%; p = 0.011) or middle cerebellar peduncles (52% versus 18%; p = 0.002) seemed more common in children who developed PFS. Young adults showed an expected lower incidence of PFS (4 out of 27; 15%), that may be due to anatomical, physiological and oncological elements. CONCLUSIONS: This study confirmed some factors known to be associated with PFS onset and shed light on other debated issues. Our findings enhance an already hypothesized role of cerebellar language lateralization. The analysis of a population of young adults may shed more light on the often-neglected existence of PFS in non-pediatric patients.

Aneurismal subarachnoid hemorrhage during the COVID-19 outbreak in a Hub and Spoke system: observational multicenter cohort study in Lombardy, Italy.

BACKGROUND: Lombardy was the most affected Italian region by the first phase of the COVID-19 pandemic and underwent urgent reorganization for the management of emergencies, including subarachnoid hemorrhage from a ruptured cerebral aneurysm (aSAH). The aim of the study was to define demographics, clinical, and therapeutic features of aSAH during the COVID-19 outbreak and compare these with a historical cohort. METHODS: In this observational multicenter cohort study, patients aged 18 years or older, who were diagnosed with aSAH at the participating centers in Lombardy from March 9 to May 10, 2020, were included (COVID-19 group). In order to minimize bias related to possible SAH seasonality, the control group was composed of patients diagnosed with aSAH from March 9 to May 10 of the three previous years, 2017-2018-2019 (pre-pandemic group). Twenty-three demographic, clinical, and therapeutic features were collected. Statistical analysis was performed. RESULTS: Seventy-two patients during the COVID-19 period and 179 in the control group were enrolled at 14 centers. Only 4 patients were positive for SARS-CoV-2. The "diagnostic delay" was significantly increased (+ 68%) in the COVID-19 group vs. pre-pandemic (1.06 vs. 0.63 days, respectively, p-value = 0.030), while "therapeutic delay" did not differ significantly between the two periods (0.89 vs. 0.74 days, p-value = 0.183). Patients with poor outcome (GOS at discharge from 1 to 3) were higher during the COVID-19 period (54.2%) compared to pre-pandemic (40.2%, p = 0.044). In logistic regression analysis, in which outcome was the dichotomized Glasgow Outcome Scale (GOS), five variables showed p-values < 0.05: age at admission, WFNS grade, treatment (none), days in ICU, and ischemia. CONCLUSIONS: We documented a significantly increased "diagnostic delay" for subarachnoid hemorrhages during the first COVID-19 outbreak in Lombardy. However, despite the dramatic situation that the healthcare system was experiencing, the Lombardy regional reorganization model, which allowed centralization of neurosurgical emergencies such as SAHs, avoided a "therapeutic delay" and led to results overall comparable to the control period.

Solitary Calvarial Metastasis As the First Presentation of Urothelial Bladder Cancer.

The most common sites of metastasis from urothelial carcinoma of the bladder include the lymph nodes, bones, lungs, liver, and peritoneum. Bladder carcinoma metastases of the head are uncommon. In the English literature, only a few cases of bladder carcinoma metastasis to the skull base have been reported, and no cases of metastasis to the calvaria have been reported previously. We present the first case of calvarial metastasis from bladder carcinoma that preceded the diagnosis of the primary tumor. Bladder calvarial metastasis as the first evidence of a primary tumor is a rare event and a sign of an advanced stage of the disease. Therefore, adequate staging is essential to ensure appropriate treatment. Surgical treatment of calvarial injuries is usually secure.

Anxiety in neurosurgical patients undergoing nonurgent surgery during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic has forced many countries into lockdown and has led to the postponement of nonurgent neurosurgical procedures. Although stress has been investigated during this pandemic, there are no reports on anxiety in neurosurgical patients undergoing nonurgent surgical procedures. METHODS: Neurosurgical patients admitted to hospitals in eastern Lombardy for nonurgent surgery after the lockdown prospectively completed a pre- and postoperative structured questionnaire. Recorded data included demographics, pathology, time on surgical waiting list, anxiety related to COVID-19, primary pathology and surgery, safety perception during hospital admission before and after surgery, and surgical outcomes. Anxiety was measured with the State-Trait Anxiety Inventory. Descriptive statistics were computed on the different variables and data were stratified according to pathology (oncological vs nononcological). Three different models were used to investigate which variables had the greatest impact on anxiety, oncological patients, and safety perception, respectively. Because the variables (Xs) were of a different nature (qualitative and quantitative), mostly asymmetrical, and related to outcome (Y) by nonlinear relationships, a machine learning approach composed of three steps (1, random forest growing; 2, relative variable importance measure; and 3, partial dependence plots) was chosen. RESULTS: One hundred twenty-three patients from 10 different hospitals were included in the study. None of the patients developed COVID-19 after surgery. State and trait anxiety were reported by 30.3% and 18.9% of patients, respectively. Higher values of state anxiety were documented in oncological compared to nononcological patients (46.7% vs 25%; p = 0.055). Anxiety was strongly associated with worry about primary pathology, surgery, disease worsening, and with stress during waiting time, as expected. Worry about positivity to SARS-CoV-2, however, was the strongest factor associated with anxiety, even though none of the patients were infected. Neuro-oncological disease was associated with state anxiety and with worry about surgery and COVID-19. Increased bed distance and availability of hand sanitizer were associated with a feeling of safety. CONCLUSIONS: These data underline the importance of psychological support, especially for neuro-oncological patients, during a pandemic.

Removal of a Frontal Sinus Osteoma and Reconstruction by a Custom-Made Implant with Neuronavigation Assistance.

The authors report the surgical treatment of an extensive right frontal sinus osteoma assisted by neuronavigation and reconstruction by a hydroxyapatite custom-made implant. The patient presents with ptosis, hypoglobus, and proptosis of the right eye, without any visual impairment. Computed tomographic (CT) scan showed a very large bony mass involving right frontal sinus and displacing the orbital roof. A stereolithographic model-guided planning was carried out to obtain a practical simulation of the surgical operation and it was submitted to a new CT scan to acquire the reference point to realize the neuronavigation assistance, and to achieve the template to realize the hydroxyapatite custom-made implant. Intraoperatively, with the help of neuronavigation assistance, osteotomies were performed by piezoelectric device. The reconstruction was made using a hydroxyapatite custom-made implant. The procedure was damage free, the bony mass was excised, and the orbital roof was repaired without any adverse effects. Postsurgical CT scan and scintigraphy showed a good reconstruction and a good-quality osteoblasts activity on the borders of the implant. Osteoma is a benign slow-growing bone tumor, usually involving the frontal sinus. Navigational assistance offers a very important help to perform safe osteotomies. Hydroxyapatite custom-made implant seems to be an excellent reconstructive method.

Arterial and microvascular supply of cerebral hemispheres in the nude mouse revealed using corrosion casting and scanning electron microscopy.

Morphological analyses of cerebral vascularization are not only important for the characterization of the anatomical and physiological relationships between vascular and nervous tissue, but also required to understand structural modifications that occur in many pathological conditions affecting the brain. The aim of this study was to generate a three-dimensional vascular map of the cerebral hemispheres in the nude mouse brain, a widely used animal model for studying tumour biology. We used the corrosion casting (CC) technique to isolate blood vessels from 30 nude mouse brains. All casts were analysed using scanning electron microscopy (SEM), which generated quantitative data regarding vessel length and diameter as well as inter-vascular and inter-branching distances. We identified three different topographical regions: (i) the cortical region, characterized by a superficial wide sheet of vessels giving rise to terminal perforant vessels that penetrate the grey matter; (ii) the inner part of the grey matter, in which dense capillary nets form many flake-like structures extending towards the grey-white matter boundary, where perforant vessels finally change direction and form a well-defined vascular sheet; and (iii) the white matter layer, characterized by a more disorganized vascular architecture. In this study, we demonstrate the accuracy of the CC-SEM method in revealing the 3D-topographical organization of the vascular network of the normal nude mouse brain. These baseline data will serve as a reference for future anatomical investigations of pathological alterations, such as tumour infiltrations, using the nude mouse model.

Septic complication following porous hydroxyapatite cranioplasty: prosthesis retention management.

After failing of autologous cranioplasty or when the bone flap is unavailable, the alloplastic (heterologous) materials are the choice for cranial reconstruction. No agreement has been reported about the material with a significant lower risk of septic complications. This is due to extremely heterogeneous prognostic factors related not only to the material used but also to the surgical procedures and/or to the timing of the procedure. More attention should be focused on the material whose characteristic could enable a delay in bacterial colonization, where an antibiotic therapy could be effective, without need of prosthesis removal. Four cases of severe septic complication following cranioplasty with porous hydroxyapatite (HA) prosthesis are presented. Patients were conservatively treated, without heterologous bone flap removal. All of our patients presented reasons for delaying HA cranioplasty removal: patients #1, 3, and 4 had an associated shunted hydrocephalus and the need for not removing the prosthesis was related to the predictable recurrence of overshunting and/or sinking skin flap syndrome. In patient #4, the revision surgery would have also damaged the microvascular flap with latissimus dorsi muscle used by plastic surgeon for skin reconstruction. In patient #2, the patient refused revision surgery. In all cases, systemic and/or radiological signs of infection were observed. In patient #2 the infective process surrounded completely the HA prosthesis, while it was located in the epidural region in patients #1 and 4. In patient #3, a surgical curettage of the infected wound was performed over the HA prosthesis. Following prosthesis retention management with antibiotic therapy, all patients revealed systemic and/or radiological signs of sepsis resolution at follow-up. The possibility to avoid a prosthesis removal with effective antibiotic treatment is mainly due to the combination of three factors: targeted antibiotic therapy, good anatomical area revascularization (resulting of an "in situ" intake of antibiotics), and the biomimetism of HA prosthesis. Further investigations in a larger number of cases need to confirm these observations.

Early Carotid Occlusion After Endarterectomy in a Patient With a Mutation for MTHFR A1298C Polymorphism.

INTRODUCTION: Significant carotid stenosis is a well-documented risk factor for ischemic stroke. Carotid endarterectomy (CEA) and carotid artery stenting are effective procedures for the prevention of stroke in patients with this disease. However, the occurrence of restenosis could contribute to an increase in the risk of ischemic stroke. CASE REPORT: A 79-year-old woman was admitted to the Neurosurgical Department to undergo a CEA because of a progressive stenosis. At the 3-month radiologic follow-up, the examinations showed a carotid restenosis. She was immediately started on a double-antiplatelet therapy. Blood samples revealed high levels of homocysteine and genetic tests showed a homozygous mutation for methylene tetrahydrofolate reductase A1298C polymorphism. Folic acid associated with pyridoxine was added to the treatment. Radiologic follow-ups showed no changes in the stenosis degree. CONCLUSIONS: Even if the association between homocysteine and carotid restenosis after CEA is unclear, an initial screening before the surgical procedure could be useful to promptly treat this condition and probably reduce the risk of this complication. In the case of homozygous mutation, the selection of patients and the appropriate therapy could reduce the risk of carotid restenosis.

Brain tumor location influences the onset of acute psychiatric adverse events of levetiracetam therapy: an observational study.

To explore possible correlations among brain lesion location, development of psychiatric symptoms and the use of antiepileptic drugs (AEDs) in a population of patients with brain tumor and epilepsy. The medical records of 283 patients with various types of brain tumor (161 M/122 F, mean age 64.9 years) were analysed retrospectively. Patients with grade III and IV glioma, previous history of epileptic seizures and/or psychiatric disorders were excluded. Psychiatric symptoms occurring after initiation of AED therapy were considered as treatment emergent psychiatric adverse events (TE-PAEs) if they fulfilled the following conditions: (1) onset within 4 weeks after the beginning of AED therapy; (2) disappearance on drug discontinuation; (3) absence of any other identified possible concurrent cause. The possible influence of the following variables were analysed: (a) AED drug and dose; (b) location and neuroradiologic features of the tumor, (c) location and type of EEG epileptic abnormalities, (d) tumor excision already or not yet performed; (e) initiation or not of radiotherapy. TE-PAEs occurred in 27 of the 175 AED-treated patients (15.4%). Multivariate analysis showed a significant association of TE-PAEs occurrence with location of the tumor in the frontal lobe (Odds ratio: 5.56; 95% confidence interval 1.95-15.82; p value: 0.005) and treatment with levetiracetam (Odds ratio: 3.61; 95% confidence interval 1.48-8.2; p value: 0.001). Drug-unrelated acute psychiatric symptoms were observed in 4 of the 108 AED-untreated patients (3.7%) and in 7 of the 175 AED-treated patients (4%). The results of the present study suggest that an AED alternative to levetiracetam should be chosen to treat epileptic seizures in patients with a brain tumor located in the frontal lobe to minimize the possible onset of TE-PAEs.

Multilobed cystic dilation of the ventriculus terminalis (CDVT).

The cystic dilation of ventriculus terminalis (CDVT) is a rare anatomical variant in adulthood. In this report we describe a new case of an adult with multilobed CDVT, causing low-back pain and subjective disturbances in walking. A myelotomy with fenestration of the cyst was performed with a good clinical and radiological outcome.