The role of neurosurgeon in the multidisciplinary approach to ectopic or bifocal intracranial germinoma: A systematic review and report of two illustrative cases.

BACKGROUND: Pure germinoma typically originates from the midline and is usually found in the pineal and suprasellar regions in 76-90 % of cases. When it is in both regions, it is considered bifocal (10 % at diagnosis). If pure germinoma is located outside of the midline, it is considered ectopic, with a global incidence of about 0.7 %. The study aims to describe the clinical and surgical approach to patients with atypical intracranial ectopic germinoma (IEG) and bifocal germinoma (BG) through a literature review with the goal to delineate the correct diagnostic and therapeutic pathway, to reduce the diagnostic delay and improve the prognosis of these patients. METHODS: A systematic review of the literature in most common electronic database (PubMed, Ovid MEDLINE and Ovid EMBASE) on IEG and BG, in according with the "PRISMA statement" criteria, from January 1990 to September 2022 was done. In addition, two rare cases of IEG and BG were reported. RESULTS: This systematic review included 16 papers (20 patients) with a final diagnosis of IEG and 30 papers (121 patients) with a final diagnosis of BG. IEGs seems to involve primary basal ganglia (40 %) and corpus callosum (40 %). For IEGs, biopsy (70 %, 14 cases out of 20) was the most common surgical approach: open approach (35 %), stereotactic minimally invasive approach (30 %) or endoscopic trans-sphenoidal approach (5 %). Partial resection was performed in 10 % of cases, whereas a total resection was performed in 20 % of cases. Also for BGs, biopsy was the most common surgical approach in 80 % of patients, whereas surgical resection (partial or total) was performed in 5.3 % of patients. CONCLUSION: IEG and BG are rare type of primary intracranial germ cell tumor, whose unusual location often can cause delays in diagnosis, which can have a significant impact on the patient's prognosis and requiring a multidisciplinary and timely approach.

Hearing preservation surgery for vestibular schwannoma: a systematic review and meta-analysis.

The aim of this systematic review is to analyse the role of hearing preservation surgery for vestibular schwannoma. The complications and hearing outcomes of the single surgical techniques were investigated and compared with those of less invasive strategies, such as stereotactic radiotherapy and wait and scan policy. This systematic review and meta-analysis was performed according to the PRISMA guidelines. All included studies were published in English between 2000 and 2022. Literature data show that hearing preservation is achieved in less than 25% of patients after surgery and in approximately half of cases after stereotactic radiotherapy, even if data on long-term preservation are currently not available.

Intracranial mesenchymal tumor with (novel) COX14::PTEN rearrangement.

Mesenchymal tumors of the central nervous system (CNS) include numerous entities, with different pathological features and biological behavior. Mesenchymal non-meningothelial tumors are rare and comprise neoplasms that are exclusive to the CNS or show peculiar features when occurring in the CNS compared with other sites. Within this group there are three new entities, classified on the basis of specific molecular alterations and included in the 5th edition of the WHO Classification of CNS Tumors: primary intracranial sarcoma; DICER1-mutant; CIC-rearranged sarcoma; intracranial mesenchymal tumor, FET::CREB fusion-positive. These tumors often show variable morphology, making diagnosis very challenging, although the implementation of molecular techniques has led to better characterization and more precise identification of these entities. However, many molecular alterations have yet to be discovered and some recently reported CNS tumors are currently missing an appropriate classification. Herein, we report the case of a 43-year-old man who presented with an intracranial mesenchymal tumor. Histopathological examination showed a wide spectrum of peculiar morphological features and a non-specific immunohistochemical profile. Whole transcriptome sequencing revealed the presence of a novel genetic rearrangement involving COX14 and PTEN genes, which has never been reported before in any other neoplasm. The tumor did not cluster in any defined methylation class of the brain tumor classifier, but resulted in a calibrated score of 0.89 for the methylation class "Sarcoma, MPNST-like", when analyzed by the sarcoma classifier. Our study is the first to report about this tumor with unique pathological and molecular features, characterized by a novel rearrangement between COX14 and PTEN genes. Other studies are necessary in order to define it as a new entity or as a novel rearrangement involving recently described and incompletely characterized CNS mesenchymal tumors.

Cerebrospinal Fluid Lactate and Glucose Levels as Predictors of Symptomatic Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a complex neurovascular syndrome with profound systemic effects associated with high rates of disability and mortality. Delayed cerebral ischemia (DCI), which encompasses all neurobiological events occurring in the subacute-late stage after aSAH, has a complex pathogenesis and can occur in the absence of instrumental vasospasm. Our aim was to assess the correlation between cerebrospinal fluid (CSF) lactate and glucose levels measured on the second or third day after aSAH with clinical deterioration caused by DCI and with 3-month functional outcome. METHODS: This prospective study included all aSAH patients admitted between January 2020 and December 2021 who underwent external ventricular drain placement and CSF lactate and glucose measurement. RESULTS: Among 133 aSAH patients, 48 had an external ventricular drain placed and early CSF lactate and glucose assessment. Independent predictors of symptomatic DCI were World Federation of Neurosurgical Societies grade IV-V (adjusted odds ratio [aOR] 25.8, 95% confidence interval [CI] 2.9-649.2, P = 0.012), elevated CSF glucose (aOR 28.8, 95% CI 3.3-775.2, P = 0.010), and elevated CSF lactate (aOR 14.7, 95% CI 1.9-205.7, P = 0.018). The only independent predictor of 3-month functional outcome was occurrence of symptomatic DCI (aOR 0.02, 95% CI 0.0-0.2, P = 0.01). CONCLUSIONS: Elevated CSF lactate and glucose levels in the first 3 days following aSAH were independent predictors of subsequent DCI-related neurological impairment; the presence of instrumental vasospasm was not significantly correlated with DCI after multivariate adjustment. CSF lactate and glucose monitoring may represent a point-of-care test, which could potentially improve prediction of subacute neurological worsening and guide therapeutic choices. Further research with larger prospective cohorts is warranted.

Anatomical study of the thoracolumbar radiculomedullary arteries, including the Adamkiewicz artery and supporting radiculomedullary arteries.

OBJECTIVE: The aim of this paper was to identify and characterize all the segmental radiculomedullary arteries (RMAs) that supply the thoracic and lumbar spinal cord. METHODS: All RMAs from T4 to L5 were studied systematically in 25 cadaveric specimens. The RMA with the greatest diameter in each specimen was termed the artery of Adamkiewicz (AKA). Other supporting RMAs were also identified and characterized. RESULTS: A total of 27 AKAs were found in 25 specimens. Twenty-two AKAs (81%) originated from a left thoracic or a left lumbar radicular branch, and 5 (19%) arose from the right. Two specimens (8%) had two AKAs each: one specimen with two AKAs on the left side and the other specimen with one AKA on each side. Eight cadaveric specimens (32%) had 10 additional RMAs; among those, a single additional RMA was found in 6 specimens (75%), and 2 additional RMAs were found in each of the remaining 2 specimens (25%). Of those specimens with a single additional RMA, the supporting RMA was ipsilateral to the AKA in 5 specimens (83%) and contralateral in only 1 specimen (17%). The specimens containing 2 additional RMAs were all (100%) ipsilateral to their respective AKAs. CONCLUSIONS: The segmental RMAs supplying the thoracic and lumbar spinal cord can be unilateral, bilateral, or multiple. Multiple AKAs or additional RMAs supplying a single anterior spinal artery are common and should be considered when dealing with the spinal cord at the thoracolumbar level.

Pituitary Stalk Hemangioblastoma: Complete Resection through Orbitozygomatic Approach with Extradural Anterior Clinoidectomy.

Background Pituitary stalk hemangioblastomas (PSHBLs) are rare vascular tumors and their surgical removal is challenging due to the proximity with several fundamental anatomic structures including the pituitary stalk, third ventricle, hypothalamus, and optic pathways. To date, only few descriptions of transcranial and transsphenoidal approaches for PSHBLs have been reported in the literature and none in video, with suboptimal outcomes in terms of pituitary function preservation. Here, we describe the use of orbitozygomatic (OZ) craniotomy with extradural anterior clinoidectomy (EAC) for the removal of a PSHBL with preservation of the pituitary stalk. Case Description A 60-year-old woman with a sporadic symptomatic HBL of the pituitary stalk, with the typical features of avid contrast enhancement on T1- and flow voids on T2-weighted magnetic resonance imaging (MRI) images, underwent a right OZ craniotomy with EAC. The choice of the approach was guided by the necessity of exposing the floor of the 3rd ventricle and infundibulum, where the origin of the pituitary stalk is better appreciated and preserved, without brain retraction. EAC was deemed important due to the necessity of widening the right carotico-oculomotor and opticocarotid triangles and gaining access to the ophthalmic segment of the internal carotid artery, origin of the superior hypophyseal artery, and the tumor supply. The postoperative MRI confirmed gross tumor removal with preservation of the pituitary stalk and no tumor recurrence after 2 years of follow-up. Conclusion OZ craniotomy coupled with EAC facilitates surgical removal of PSHBLs thus augmenting the chances of pituitary function preservation. The link to the video can be found at https://youtu.be/hH65W937RGY .

Postoperative Impact of Pontocerebellar Angle Surgery on the Quality of Life in Patients with Vestibular Schwannoma.

BACKGROUND: Vestibular Schwannomas are benign tumors arising from the VIII CN. Surgical treatment is indicated in case of tumors larger than 2.5 cm in the cerebellopontine angle or in the case of cranial nerve dysfunction. The aim of the present study was to evaluate the QoL by means of the PANQOL questionnaire in a group of surgically treated patients mainly affected by large and giant VS Methods: All patients underwent preoperative and postoperative otoneurological evaluation and gadolinium enhanced MRI and they completed, independently, the PANQOL questionnaire at last follow up. RESULTS: 70% of patients presented with large Koos III or IV VS Each domain of PANQOL showed a strong correlation with the total PANQOL score. In relation to the postoperative facial nerve function, patients with poorer function showed significantly lower score in the facial dysfunction and pain, patients with postoperative balance problems showed a significantly lower PANQOL score for domains of balance and pain. CONCLUSIONS: This study showed that postoperative QoL of patients was acceptable even if there were some domains that were more affected, such as hearing and balance domains; therefore, the lowest scores suggest the need for vestibular rehabilitation programs and strategies that improve postoperative hearing.

The Readthrough Isoform AQP4ex Is Constitutively Phosphorylated in the Perivascular Astrocyte Endfeet of Human Brain.

AQP4ex is a recently discovered isoform of AQP4 generated by a translational readthrough mechanism. It is strongly expressed at the astrocyte perivascular endfeet as a component of the supramolecular membrane complex, commonly called orthogonal array of particles (OAP), together with the canonical isoforms M1 and M23 of AQP4. Previous site-directed mutagenesis experiments suggested the potential role of serine331 and serine335, located in the extended peptide of AQP4ex, in water channel activity by phosphorylation. In the present study we evaluated the effective phosphorylation of human AQP4ex. A small scale bioinformatic analysis indicated that only Ser335 is conserved in human, mouse and rat AQP4ex. The phosphorylation site of Ser335 was assessed through generation of phospho-specific antibodies in rabbits. Antibody specificity was first evaluated in binding phosphorylated peptide versus its unphosphorylated analog by ELISA, which was further confirmed by site-directed mutagenesis experiments. Western blot and immunofluorescence experiments revealed strong expression of phosphorylated AQP4ex (p-AQP4ex) in human brain and localization at the perivascular astrocyte endfeet in supramolecular assemblies identified by BN/PAGE experiments. All together, these data reveal, for the first time, the existence of a phosphorylated form of AQP4, at Ser335 in the extended sequence exclusive of AQP4ex. Therefore, we anticipate an important physiological role of p-AQP4ex in human brain water homeostasis.

Alteration of the translational readthrough isoform AQP4ex induces redistribution and downregulation of AQP4 in human glioblastoma.

Glioblastoma multiforme (GBM) is characterized by a remarkable cellular and molecular heterogeneity that make the behavior of this tumor highly variable and resistant to therapy. In addition, the most serious clinical complication of GBM and other brain tumors is the development of vasogenic edema which dramatically increase the intracranial pressure. In the present study we evaluate the expression, supramolecular organization and spatial distribution of AQP4 and AQP4ex, the new readthrough isoform of AQP4, in relationship with the degree of vasogenic brain edema and tumor progression. To this purpose, tissue samples from regions of tumor core, peritumoral and non-infiltrated tissues of each GBM patient (n = 31) were analyzed. Immunofluorescence experiments revealed that the expression of AQP4ex was almost absent in tumoral regions while the canonical AQP4 isoforms appear mostly delocalized. In peritumoral tissues, AQP4 expression was found altered in those perivascular astrocyte processes where AQP4ex appeared reduced and partially delocalized. Protein expression levels measured by immunoblot showed that global AQP4 was reduced mainly in the tumor core. Notably, the relative amount of AQP4ex was more severely reduced starting from the peritumoral region. BN-PAGE experiments showed that the supramolecular organization of AQP4 is only partially affected in GBM. Edema assessment by magnetic resonance imaging revealed that the level of AQP4ex downregulation correlated with edema severity. Finally, the degree of BBB alteration, measured with sodium fluorescein content in GBM biopsies, correlated with the edema index and AQP4ex downregulation. Altogether these data suggest that the AQP4ex isoform is critical in the triggering event of progressive downregulation and mislocalization of AQP4 in GBM, which may affect the integrity of the BBB and contributes to accumulation of edema in the peritumoral tissue. Thus, AQP4ex could be considered as a potential early biomarker of GBM progression.

A Rare Case of Posterior Fossa Tumor and Central Precocious Puberty: Case Presentation and Review of the Literature.

Central precocious puberty (CPP) is a condition that causes early gonadotropin-dependent sexual development; CPP is idiopathic in girls in most cases, whereas more than 50% of boys have an identifiable etiology. We conducted a qualitative systematic review following the ENTREQ (enhancing transparency in reporting the synthesis of qualitative research) framework. A search was made in MEDLINE/Pubmed and MeSH Database using the terms "precocious puberty" AND "brain tumor" OR "posterior fossa tumor" OR "cerebellar tumor" OR "infratentorial tumor", identifying five cases of pediatric patients with infratentorial tumors and CPP and a case of cerebellar ganglioglioma without hypothalamic-pituitary-gonadal axis involvement and/or intracranial hypertension. Our work highlights the importance of a multidisciplinary approach and extensive central nervous system imaging for patients presenting with CPP in order to detect possible tumor association. Moreover, we believe that this manuscript could contribute to stimulate other research because the exact mechanism of CPP in infratentorial brain lesions has not been understood yet.

Papillary Meningioma: Case Presentation with Emphasis on Surgical and Medical Therapy of a Rare Variant of Meningioma.

Meningioma is one of the most frequent neoplasms of all in the central nervous system. Different variants are known, and of these some have peculiar characteristics, both from a morphological point of view and from a biological point of view. Here, we present a rare case of relapsed papillary meningioma in a young patient, focusing on histological characteristics, medical-surgical therapy and focusing on the risk of progression and/or recurrence of the lesion if not completely eradicated. Finally, we provide detailed molecular characteristics of the case in question.

Primary Endoscopic Endonasal Management of Giant Pituitary Adenomas: Outcome and Pitfalls from a Large Prospective Multicenter Experience.

PURPOSE: To evaluate factors influencing clinical and radiological outcome of extended endoscopic endonasal transtuberculum/transplanum approach (EEA-TTP) for giant pituitary adenomas (GPAs). METHODS: We recruited prospectively all consecutive GPAs patients undergoing EEA-TTP between 2015 and 2019 in 5 neurosurgical centers. Preoperative clinical and radiologic features, visual and hormonal outcomes, extent of resection (EoR), complications and recurrence rates were recorded and analyzed. RESULTS: Of 1169 patients treated for pituitary adenoma, 96 (8.2%) had GPAs. Seventy-eight (81.2%) patients had visual impairment, 12 (12.5%) had headaches, 3 (3.1%) had drowsiness due to hydrocephalus, and 53 (55.2%) had anterior pituitary insufficiency. EoR was gross or near-total in 46 (47.9%) and subtotal in 50 (52.1%) patients. Incomplete resection was associated with lateral suprasellar, intraventricular and/or cavernous sinus extension and with firm/fibrous consistence. At the last follow-up, all but one patient (77, 98.7%) with visual deficits improved. Headache improved in 8 (88.9%) and anterior pituitary function recovered in 27 (50.9%) patients. Recurrence rate was 16.7%, with 32 months mean recurrence-free survival. CONCLUSIONS: EEA-TTP is a valid option for GPAs and seems to provide better outcomes, lower rate of complications and higher EoR compared to one- or multi-stage microscopic, non-extended endoscopic transsphenoidal, and transcranial resections.

A Unique Case of Bilateral Thalamic High-Grade Glioma in a Pediatric Patient with LI-Fraumeni Syndrome: Case Presentation and Review of the Literature.

Li-Fraumeni syndrome (LFS) is a rare high-penetrance and autosomal-dominant pathological condition caused by the germline mutation of the TP53 gene, predisposing to the development of tumors from pediatric age. We conducted a qualitative systematic review following the ENTREQ (Enhancing Transparency in Reporting the Synthesis of Qualitative Research) framework. A search was made in MEDLINE/Pubmed and MeSH Database using the terms "Li-Fraumeni" AND "pediatric high-grade glioma (HGG)", identifying six cases of HGGs in pediatric patients with LFS. We added a further case with peculiar features such as no familiar history of LFS, association of embryonal rhabdomyosarcoma and bithalamic HGG, whose immunohistochemical profile was accurately defined by Next Generation Sequencing. Knowledge synthesis and case analysis grounded the discussion about challenges in the management of this pathology in pediatric age.

Dalbavancin Efficacy and Impact on Hospital Length-of-Stay and Treatment Costs in Different Gram-Positive Bacterial Infections.

BACKGROUND AND OBJECTIVES: The study aimed to evaluate the impact of dalbavancin therapy on both hospital length-of-stay (LOS) and treatment-related costs, as well as to describe the clinical outcome, in a retrospective cohort of patients with diverse Gram-positive bacterial infections, hospitalized in different specialty Units. METHODS: From July 2017 to July 2019, clinical and sociodemographic data were collected for all hospitalized patients switched to dalbavancin for the treatment of Gram-positive infections. LOS and treatment-related costs were assessed and compared to a hypothetical scenario where the initial standard antimicrobial therapy would have been administered in hospital for the same duration as dalbavancin. RESULTS: A total of 50 patients were enrolled. The observed infections were: acute bacterial skin and skin structure infections (ABSSSIs, 12 patients), complicated ABSSSIs (eight patients), osteoarticular infections (18 patients), vascular graft or cardiovascular implantable electronic devices (CIED) infections (12 patients). After a median of 14 [interquartile range (IQR) 7-28] days, the in-hospital antimicrobial therapy was switched to dalbavancin 1500 mg. When appropriate, considering the site and the clinical course of the infection, 1500 mg doses were repeated every 14 days until recovery. Overall, 49/50 (98%) patients reported clinical success at the end of therapy. No relapses were observed in 37 patients for whom a median follow-up of 150 (IQR 30-180) days was available. By switching to dalbavancin, a median of €8,259 (IQR 5644-17,270) and 14 hospital days (IQR 22-47) per patient were saved. CONCLUSIONS: In this experience, the use of dalbavancin contributed to shorten LOS and treatment-related costs, especially in difficult Gram-positive infections requiring prolonged therapy.

Ruptured Tentorial Arteriovenous Fistula: Endoscopic-Assisted Microsurgical Disconnection Using Indocyanine Green Videoangiography Guidance.

Tentorial dural arteriovenous fistulas are rare causes of intracranial hemorrhage and nervous tissue venous congestion. Due to their extensive arterial supply and difficult transvenous endovascular navigation, they are frequently managed microsurgically. Precise identification of the venous drainage, its retractorless exposition, and real-time verification of arteriovenous disconnection are the mainstays of surgery. We describe the case of 61-year-old man presenting with a cerebellar hematoma causing obstructive hydrocephalus, resolved by emergent endoscopic third ventriculocisternostomy, with no need of external ventricular drain.1 Brain angiograms showed a straight sinus dural arteriovenous fistula. The fistulous point could not be reached endovascularly due to the small caliber and tortuosity of the arterial feeders and difficult transvenous navigation, and then the endovascular treatment was limited to closure of both occipital arteries. At surgery, indocyanine green videoangiography with semiquantitative assessment of flow dynamics identified the draining vein originating from the dura of the left wall of the straight sinus (Video 1). After the draining vein was clipped at its origin from the straight sinus and the endoscopic view confirmed that the clip's tips straddled the vein, control indocyanine green videoangiography showed no more early injection of the draining vein and restoration of the normal venous drainage. Postoperative angiograms confirmed the elimination of the fistula. The patient was discharged to a rehabilitation facility 5 days postoperatively and regained functional independence, with a modified Rankin Scale score of zero by the third month after surgery. Relevant teaching points are exposed at the end of the case narration.