To use or not to use antithrombotics in unruptured cerebrovascular malformations? A systematic review focusing on this clinical and surgical dilemma.

OBJECTIVE: Antithrombotic medications (ATMs), including antiplatelet therapy (APT) and oral anticoagulants (OACs), are widely used in current clinical practice for the prevention and treatment of a variety of cardiovascular diseases, deep vein thrombosis, and pulmonary thromboembolisms. The long-term usage of these drugs, associated with an inherent risk of bleeding, raises concerns for unruptured cerebrovascular malformations (UCVMs), such as arteriovenous malformations (AVMs), cerebral cavernous malformations (CCMs), and intracranial aneurysms (IAs), in which the bleeding risk also poses a major threat. The aim of this study was to assess the safety and risk-benefit ratio of ATMs in these various neurosurgical diseases and to give neurosurgeons a safe and reasonable choice regarding whether to administer ATMs to these patients during the course of the disease. METHODS: The authors conducted a systematic review of the literature (PubMed/MEDLINE and Embase) according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines, which yielded 4 papers about CCMs, 2 about AVMs, and 9 about IAs. The risk of bias was assessed using the Cochrane Collaboration's tool. RESULTS: For AVMs, only 2 studies with a total of only 14 patients were included. Data on AVMs and ATMs are limited and weak, relying on small case series. Nevertheless, there is no evidence for either an increased risk of intracranial hemorrhage in patients with AVMs who are receiving ATMS or the need to interrupt ATMs in those patients who have been diagnosed with sporadic, unruptured brain AVMs. With respect to CCMs, the literature search resulted in 4 cohort studies and 1 meta-analysis. These studies affirmed the absence of a correlation between ATMs and an increased risk of CCM bleeding while simultaneously suggesting a protective role of ATMs against bleeding. Concerning IAs, the topic is more complex and debated, despite larger case series on IAs than on AVMs or CCMs. The benefits of ATMs for IAs may vary according to the type of intervention and specific drug administered. Evidence supports the continuation of long-term APT for all patients newly diagnosed with an IA, whereas starting APT in patients with incidentally discovered IA as a means of prophylaxis against rupture is unclear. CONCLUSIONS: The findings of this review should be taken as a wide overview of UCVM and ATM. Future research should consider the relationship of AVM, CCM, and IA with APT and OAC independently.

Practical Algorithm for the Management of Multisutural Craniosynostosis with Associated Chiari Malformation and/or Hydrocephalus.

INTRODUCTION: The association between multisutural craniosynostosis with Chiari malformation (CM), venous hypertension, and hydrocephalus is widely described in the literature, especially in children with paediatric craniofacial syndromes. Some efforts have been done in the last years to understand the complex pathogenetic mechanisms underlying this association, and several theories have been proposed. In particular, it is now accepted that the hypothesis of the overcrowding of the posterior fossa due to precocious suture fusion is the cause of the cerebellar herniation in syndromic and non-syndromic patients, against the theory of intrinsic cerebellar anomalies, ventriculomegaly, and venous hypertension. However, whatever the pathophysiological mechanism, it is still unclear what the best management and treatment of CM and hydrocephalus are in multisutural craniosynostosis patients. The aim of this study was to report our 25 years' experience in treating paediatric patients affected by these rare pathologies in order to propose a simple and effective therapeutic flow chart for their management. MATERIALS AND METHODS: We retrospectively collected data of each patient who underwent a cranial vault remodelling (CVR) for complex multisutural craniosynostosis in our institution in the last 25 years, while monosutural craniosynostosis was excluded. We recorded data concerning type of craniosynostosis and craniofacial syndromes, presence of ventriculomegaly, and CM at presentation and clinical and radiological follow-up. Therefore, we evaluated the final outcomes (improved, stable, deteriorated) of these patients and created a practical flow chart that could help physicians choose the best surgical treatment when different pathological conditions, as Chiari malformation I (CMI) or hydrocephalus, affect complex craniosynostosis children. RESULTS: Thirty-nine patients (39 out of 55; 70.9%), with an isolated multisutural craniosynostosis at presentation, underwent a two-step CVR as first surgery; 36 patients (92.3%) had an improved outcome, 2 patients (5.1%) had a stable outcome, and 1 patient (2.56%) had a deteriorated outcome. Other eight children (8 out of 55; 14.5%) had a radiological evidence of asymptomatic CMI at presentation. In this group, we performed CVR as first surgery. As for the final outcome, 7 patients had an improved outcome (87.5%) with good aesthetic result and stability or resolution of CMI. Finally, 7 patients (7 out of 55; 12.7%) presented a various combination of CMI and ventriculomegaly or hydrocephalus at presentation. Among them, 3 patients had an improved outcome (42.8%), and 4 patients had a deteriorated outcome (57.1%). DISCUSSION: The prevalence of one pathological condition with associated symptoms over the others was the key factor leading our therapeutic strategy. When craniosynostosis is associated with a radiological CM, the assessment of clinical symptoms is of capital importance. When asymptomatic or pauci-symptomatic, we suggest a CVR as first step, for its efficacy in reducing tonsillar herniation and solving CM symptoms. When craniosynostosis is associated with ventricular enlargement, the presence of intracranial hypertension signs and symptoms forces physicians to first treat hydrocephalus with a ventriculo-peritoneal shunt or endoscopic third ventriculostomy. For patients with various degrees and severity of ventriculomegaly and associated CM, the outcomes were very heterogeneous, even when the same therapeutic strategy was applied to patients with similar starting conditions and symptoms. This is maybe the most unexpected and least clear part of our results. Despite the proposed algorithm comes from a clinical experience on 85% successfully treated patients with multiple craniosynostosis, more extensive and deep studies are needed to better understand CM and hydrocephalus development in such conditions.

Turning tables: a war-like approach to neurosurgical emergencies in the COVID-19 era.

During the Coronavirus-disease-2019 (COVID-19) pandemic emergency, neurosurgeons may have to decide to prioritize treatments to patients with the best chance of survival, as in a war setting triage. In this paper, we discussed factors that should be considered in the perioperative period and neurocritical care management of neurosurgical patients during a pandemic emergency; in particular, we focused on the decision on whether to operate or not a patient during the COVID-19 pandemic. A multidisciplinary expert panel composed by specialists with direct experience in COVID-19 management discussed and reviewed the criteria that should be taken into account in the decision to operate or not a patient during the COVID-19 pandemic. Disease-related factors should be first considered in order to precisely know the enemy we are facing. Patient-related factors should be then evaluated to understand the battleground on which we are facing the enemy. After these considerations, we must ascertain costs and expected outcomes of our surgical intervention by evaluation of surgery-related factors. Finally, the last factor that need to be evaluated before surgery is the availability of resources, staff, and ward availability for perioperative care. All these considerations will lead to the optimal organization and management of neurosurgical emergencies during pandemic times, considering the community and not only the single patient. We provided schematic preoperative considerations that we hope will help neurosurgeons to guide their decisions in these challenging times.

De novo intracranial aneurysm formation in SARS-CoV-2 infection: first report of a yet unknown complication.

BACKGROUND AND IMPORTANCE: COVID-19 is a viral infection that mainly affects the respiratory tract, but can also cause multiple inflammatory reactions, including neurological and cerebrovascular manifestations. We report the case of a COVID-19 patient who developed 'de novo' multiple cerebral aneurysms with no risk factors for aneurysm formation. CLINICAL PRESENTATION: A 55-year-old man with SARS-CoV-2 infection came to our attention for left eye blindness accompanied by ptosis, palpebral chemosis and retro-orbital pain. Brain CT and CT-angiography were negative for hemorrhages and for vascular malformations. Repeated intracerebral hemorrhages and neurological deterioration then occurred, and a new CT-angiography showed multiple intracranial aneurysms that were not present before. CONCLUSION: Intracranial aneurysm formation as a complication of COVID-19 has not been previously reported. As other viral infections do, COVID-19 may be able to determine a vascular damage that can ultimately lead to development of an aneurysm. It is reasonable to hypothesize an involvement of the renin-angiotensin system as a pathogenic mechanism. A conservative therapy aiming at inflammatory modulation and vascular damage prevention may be warranted in these patients.

Lymphoplasmacyte-rich meningioma with hematologic signs and PD-L1 over-expression.

Lymphoplasmacyte-rich meningioma (LPRM) is one of the rarest variants of grade I meningiomas. It can be clinically associated with prominent peripheral blood abnormalities, anemia, and/or various gammopathy, which usually disappear after surgical removal of the tumor. We document a case of right frontal LPRM in a 72-year-old male who presented general cognitive decadence. The patient suffered from mild anemia. The LPRM is a rare variant of meningioma, with only a few cases globally reported in the literature. It has been categorized as a grade I tumor in the 2021 World Health Organization (WHO) classification central nervous system. Due to the rarity, this meningioma variant origin and biological behavior are still not clear. Immunohistochemistry profile showed prominent PD-L1 expression, leading to additional interrogation on LPRM immunomorphological characteristics, the significance of the inflammatory tumoral microenvironment and its correlation with the immune-checkpoints.

Peculiar bony involvement of sinus pericranii in children: Extensive diploic erosion in three "karstic" variants.

OBJECT: Sinus pericranii (SP) is a rare, benign, extradural venous anomaly whose extracranial connection consists in an enlarged subgaleal drainage composed of a network of thin-walled veins that form a varix on the external table of the skull. In the present series of three patients we present three variantesof SP which have never been described, characterized by an extensive diploic erosion causing a "karstic" effect. METHODS: A systematic review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A comprehensive search for relevant articles was performed on PubMed from 1992 to 2022 using the following search words: "sinus pericranii". RESULTS: The search produced 77 articles with 137 patients. In all the cases analysed, there were not reported any patients with extensive diploic erosion, namely "karstic" variants. So, the authors present clinical history, neuroimages, treatment strategies and outcome of 3 patients with a "karstic" SP with the aim to describe this clinicradiological entity. CONCLUSIONS: In this study, our group identified a peculiar variant of SP characterized by bony involvement with extensive diploic "karstic" erosion of diploe, with possible tendency to enlarge during time.

Preliminary Validation of FoRCaSco: A New Grading System for Cerebral and Cerebellar Cavernomas.

OBJECTIVE: Surgical indications for cerebral cavernous malformations (CCMs) remain significantly center- and surgeon-dependent; available grading systems are potentially limited, as they do not include epileptologic and radiologic data. Several experienced authors proposed a new grading system for CCM and the first group of patients capable of providing its statistical validation was analyzed. METHODS: A retrospective series of 289 CCMs diagnosed between 2008 and 2021 was collected in a shared anonymous database among 9 centers. The new grading system ranges from -1 to 10. For each patient with cortical and cerebellar cavernous malformations the grading system was applied, and a retrospective outcome analysis was performed. We proposed a score of 4 as a cutoff for surgical indication. RESULTS: Operated patients with a score ≥4 were grouped with non-operated patients with a score <4, as they constituted the group that received correct treatment according to the new grading system. Patients with a score ≥4, who underwent surgery and had an improved outcome, were compared to patients with a score ≥4 who were not operated (P = 0.04), and to patients with a score <4 who underwent surgery (P < 0.001). CONCLUSIONS: This preliminary statistical analysis demonstrated that this new grading would be applicable in surgical reality. The cutoff score of 4 correctly separated the patients who could benefit from surgical intervention from those who would not. The outcome analysis showed that the treated patients in whom the grading system has been correctly applied have a better outcome than those in whom the grading system has not been applied.

Pediatric pituitary adenoma with mixed FSH and TSH immunostaining and FSH hypersecretion in a 6 year-old girl with precocious puberty: case report and multidisciplinary management.

OBJECTIVE: We describe a rare case of functioning gonadotropins-producing pediatric adenoma immunostaining positively for FSH and focally for TSH causing central precocious puberty associated to central hypothyroidism in a 6 year-old girl. MATERIALS AND METHODS: Clinical evaluation revealed precocious puberty, as confirmed by hormonal determination with elevated FSH and estradiol, while central hypothyroidism was biochemically diagnosed by a low fT4 and normal TSH. Head MRI showed the presence of a hyperintense pituitary lesion. The patient successfully underwent transsphenoidal endoscopic resection of the pituitary macroadenoma. RESULTS: Pathologic evaluation of the tissue resected at surgery confirmed the diagnosis of pituitary adenoma with positive immunohistochemistry for FSH and focally for TSH in a mixed pattern. Ten months after surgery, there were no neurological signs and symptoms. Postoperative head MRI showed no abnormalities and no evidence of tumor regrowth. CONCLUSIONS: Early and accurate diagnosis, multidisciplinary approach and close follow up are crucial factors for the favorable outcome.

Evaluation of acromegaly treatment direct costs with respect to biochemical control and follow-up length.

PURPOSE: Acromegaly is a severe chronic endocrine disease. Achieving biochemical control often needs a multimodal treatment approach, including prolonged medical treatment. Aim of the study is to evaluate the burden of treatment direct costs with respect to the different therapeutic strategies, disease control, and follow-up length. METHODS: Single center retrospective study on 73 acromegaly patients. Costs of acromegaly treatments were computed based on a detailed revision of patients' clinical charts. RESULTS: Median total treatment cost/patient was €47,343 during the entire follow-up (8 years), while median treatment cost/patient/year was €6811. The majority of patients received medical therapy (71/73, 97.3%). Median cost for first-line medical treatment (first-generation somatostatin receptor ligands) was lower compared to second-line treatments (pegvisomant monotherapy or combination therapies), considering both total (€22,824 vs €76,140; p < 0.001), and yearly cost/patient (€4927 vs €9161; p < 0.001). Sixty patients (82.2%) reached biochemical control at last follow-up (IGF-1 ≤ 1 xULN). The percentage of patients treated with first- or second-line medical therapies was comparable between controlled and uncontrolled patients (p = 1.000), and the yearly cost/patient did not significantly differ between the two groups (€6936 vs €6680; p = 0.829). Follow-up duration was significantly longer in controlled patients compared to the uncontrolled ones (8.7 vs 3.5 years; p = 0.019). CONCLUSIONS: Direct costs for the management of acromegaly have a significant burden on the healthcare systems. However, more than 80% of our patients reached biochemical control using multimodal approaches. Treatment modalities and yearly costs did not significantly differ between controlled and uncontrolled patients, while follow-up length represented a major determinant of biochemical outcome.

Lymphoplasmacyte-rich meningioma with hematologic signs and PD-L1 over-expression

ABSTRACT Lymphoplasmacyte-rich meningioma (LPRM) is one of the rarest variants of grade I meningiomas. It can be clinically associated with prominent peripheral blood abnormalities, anemia, and/or various gammopathy, which usually disappear after surgical removal of the tumor. We document a case of right frontal LPRM in a 72-year-old male who presented general cognitive decadence. The patient suffered from mild anemia. The LPRM is a rare variant of meningioma, with only a few cases globally reported in the literature. It has been categorized as a grade I tumor in the 2021 World Health Organization (WHO) classification central nervous system. Due to the rarity, this meningioma variant origin and biological behavior are still not clear. Immunohistochemistry profile showed prominent PD-L1 expression, leading to additional interrogation on LPRM immunomorphological characteristics, the significance of the inflammatory tumoral microenvironment and its correlation with the immune-checkpoints.

Role of Anterior Nasal Packing in Endoscopic Skull Base Surgery: Italian Survey.

BACKGROUND: Nowadays, the endoscopic endonasal approach to sellar and parasellar region tumors is a common technique in neurosurgery, and surgical nuances, complications, and management strategies are shared in a multidisciplinary setting between neurosurgeons and ear, nose, and throat surgeons. Due to the heterogeneity of its variations, the role of the anterior nasal packing in endoscopic endonasal approach to the skull base surgery (EESBS) has not yet been unanimously accepted and no consensus or guidelines on its use exist. MATERIALS AND METHODS: A survey containing 10 questions about indications, management advantages, and pitfalls of the use of anterior nasal packing in EESBS was created by using an online open-source tool (SurveyMonkey). The questionnaire was sent to 39 Italian neurosurgical departments, which routinely adopt the endoscopic endonasal approach. RESULTS: Almost half of 39 selected centers (19; 48.7%) answered our survey. The main results can be summarized as 1) anterior nasal packing after EESBS is considered useful by 84% of participants, 2) prevention of epistaxis is the principal indication for anterior nasal packing, 3) the type of approach and skull base reconstruction influence the use of anterior nasal packing, and 4) nasal discomfort is considered the principal negative aspect of nasal packing. CONCLUSIONS: Our study identified that anterior nasal packing is commonly adopted in certain conditions, namely when extensive nasal dissection is performed. Furthermore, the choice to adopt or not the anterior nasal packing should be tailored taking in account specific conditions, such as acromegaly and Cushing disease. It represents an important factor in reducing postoperative sinonasal complications of EESB.

Management of spinal aneurysms associated with arteriovenous malformations: systematic literature review and illustrative case.

PURPOSE: Spinal aneurysms are rare vascular malformations, commonly associated with spinal AVMs. AVM-associated spinal aneurysms are burdened by significant morbidity. The purpose of our study is to evaluate the best treatment strategy for these uncommon vascular lesions and to report an illustrative case. METHODS: We reviewed clinical and radiological data of a patient surgically treated at our institution for a spinal AVM with an associated prenidal aneurysm. According to PRISMA guidelines, a systematic literature review has been performed in order to discuss the best management AVM-associated prenidal aneurysms. RESULTS: In the reported case, the aneurysm showed spontaneous regression at follow-up after surgical removal of the AVM. Only 6 articles reported management of spinal prenidal AVM-associated aneurysms. Basing on our experience and data from literature, surgical treatment of the aneurysm may be indicated along with the resection of the AVM if the aneurysm is close to the nidus. Conversely, if the aneurysm is far away from the nidus or in an unfavorable position, resection of the nidus only may lead to aneurysm regression as in the reported case. CONCLUSIONS: The treatment strategy for AVM-associated spinal aneurysms should be tailored on the single patient. In presence of large aneurysms that cause mass-effect symptoms, when rupture of the aneurysm is suspected or when treatment of the AVM is not proposable, direct treatment of the aneurysm should be considered. Otherwise, when complete resection of the nidus is performed, the eventually associated unruptured aneurysms located in challenging positions can be safely managed conservatively.

The role of external ventricular drainage for the management of posterior cranial fossa tumours: a systematic review.

Posterior cranial fossa tumours frequently develop hydrocephalus as first presentation in up to 80% of paediatric patients and 21.4% of adults, although it resolves after tumour removal in 70-90% and 96%, respectively. New onset hydrocephalus is reported in about 2.1% of adult and 10-40% of paediatric patients after posterior fossa surgery. There is no consensus concerning prophylactic external ventricular drainage (EVD) placement that is frequently used before posterior fossa lesion removal, as well in those cases without clear evidence of hydrocephalus. The aim of the study was to define the most correct management for patients who undergo posterior fossa tumour surgery, thus identifying cohorts of patients who are at risk of persistent hydrocephalus prior to surgery. A systematic review of literature has been performed, following PRISMA guidelines. Most of the studies reported CSF shunt only in the presence of hydrocephalus, whereas only a few authors suggested its prophylactic use in the absence of signs of ventricular dilatation. Predictive factors for postoperative hydrocephalus has been identified, including young age (< 3 years), severe symptomatic hydrocephalus at presentation, EVD placement before surgery, FOHR index > 0.46 and Evans index > 0.4, pseudomeningocele, CSF leak and infection. The use of pre-resection CSF shunt in case of signs and symptoms of hydrocephalus is mandatory, although it resolves in the majority of cases. As reported by several studies included in the present review, we suggest CSF shunt also in case of asymptomatic hydrocephalus, whereas it is not indicated without evidence of ventricular dilatation.

Ipsilateral Nasoseptal Flap Pedicle for Transpterygoid Approach: Technical Note.

INTRODUCTION: Transpterygoid approach is an expanded endonasal approach (EEA) that allows surgical access to the medial infratemporal fossa, to the skull base area of petrous bone and to the Meckel's cave. During this approach, a sacrifice of sphenopalatine artery is often required, leading to the need of contralateral Hadad-Bassagasteguy flap (HBF) or alternative reconstructive techniques. MATERIALS AND METHODS: We report a case of spontaneous CSF leak due to a meningo-encephalocele in the left lateral recess of sphenoid sinus, in which an ispilateral nasoseptal flap was harvest and sphenopalatine artery was preserved. RESULTS: We described the surgical technique adopted to preserve the ipsilateral nasoseptal vascular pedicle during transpterygoid approach and we performed a review of the pertinent literature. CONCLUSION: Wide exposure of the pterygoid base through transpterygoid approach could be obtained preserving the sphenopalatine artery, allowing skull base reconstruction with ipsilateral nasoseptal flap.

Pediatric Neurosurgery After the COVID-19 Pandemic: Management Strategies from a Single Pediatric Hospital in Italy.

BACKGROUND: Coronavirus disease-2019 (COVID-19) pandemic had a great impact over all elective neurosurgical activity and important implications in management of neurosurgical urgencies. During the pandemic, some pediatric hospitals reported their experiences. After the emergency phase of the COVID-19 pandemic, the health care system needs to be reorganized to again manage all nonurgent activities, while ensuring safety of both patients and health care workers. METHODS: We developed preventive measures to limit any possibility of COVID-19 spread, according to the principles of epidemiologic prevention and suggestions from recent literature. To evaluate the efficacy of these measures, we retrospectively reviewed the neurosurgical activity at our institution from May 4 to July 15, 2020. RESULTS: One hundred nineteen patients were admitted to the neurosurgical ward, and 80 surgical procedures were performed. Furthermore, 130 outpatient clinics were scheduled. A total of 258 nasopharyngeal swabs and 249 specific interviews were performed. In our series, no cases of positivity for severe acute respiratory syndrome coronavirus-2 infection were found, and no surgical cases were postponed. DISCUSSION: We present the management of the neurosurgical activity after the emergency phase at the Neurosurgical Department of Giannina Gaslini Children's Hospital in Genoa, Italy. CONCLUSIONS: The Italian health care system is undertaking a process of reorganization of resources, in an attempt to restore all nonurgent activities while ensuring safety. After the emergency phase, we are learning to live together with COVID-19 and, although epidemiologic data are encouraging, we must be prepared for an eventual second peak.