Assessing the efficacy of an innovative diagnostic method for identifying 5 % variants in somatic ctDNA.

BACKGROUND: Liquid biopsy is considered a complementary and recently also an alternative method to surgical biopsy. It allows for the acquisition of valuable information regarding the potential presence of tumors, particularly through the analysis of circulating tumor DNA (ctDNA). CtDNA is a fraction of circulating free DNA (cfDNA) that can be extracted from various tissues, with blood being the most readily available. RESULTS: To maximize the yield of plasma separation, specific Streck tubes are recommended for blood collection. The MagPurix CFC DNA Extraction Kit can be used for cfDNA extraction, and the TWIST Library Preparation protocol can be optimized for further analysis. Next-generation sequencing (NGS) can be employed to compare somatic and germline lineages, enabling the identification of somatic variants with a Variant Allele Frequency (VAF) of 5 % or higher, which are absent in the germline lineage. CONCLUSION: This analysis helps in the assessment of recurrence, analysis, and monitoring of cancer tissue.

Combined Endoscopic Endonasal Transclival and Contralateral Transmaxillary Approach to the Petrous Apex and the Petroclival Synchondrosis: Working "Around the Corner" of the Internal Carotid Artery-Quantitative Anatomical Study and Clinical Applications.

The endoscopic contralateral transmaxillary (CTM) approach has been proposed as a potential route to widen the corridor posterolateral to the internal carotid artery (ICA). In this study, we first refined the surgical technique of a combined multiportal endoscopic endonasal transclival (EETC) and CTM approach to the petrous apex (PA) and petroclival synchondrosis (PCS) in the dissection laboratory, and then validated its applications in a preliminary surgical series. The combined EETC and CTM approach was performed on three cadaver specimens based on four surgical steps: (1) the nasal, (2) the clival, (3) the maxillary and (4) the petrosal phases. The CTM provided a "head-on trajectory" to the PA and PCS and a short distance to the surgical field considerably furthering surgical maneuverability. The best operative set-up was achieved by introducing angled optics via the endonasal route and operative instruments via the transmaxillary corridor exploiting the advantages of a non-coaxial multiportal surgery. Clinical applications of the combined EETC and CTM approach were reported in three cases, a clival chordoma and two giant pituitary adenomas. The present translational study explores the safety and feasibility of a combined multiportal EETC and CTM approach to access the petroclival region though different corridors.

The Posterior Auricularis Muscle as Superficial Landmark for the Sigmoid Sinus and Transverse-Sigmoid Sinus Junction: An Anatomical Study.

OBJECTIVE: Neuronavigation systems coupled with previously reported external anatomical landmarks assist neurosurgeons during intracranial procedures. We aimed to verify whether the posterior auricularis muscle (PAM) could be used as an external landmark for identifying the sigmoid sinus (SS) and the transverse-sigmoid sinus junction (TSSJ) during posterior cranial fossa surgery. METHODS: The PAM was dissected in 10 adult cadaveric heads and after drilling the underlying bone, the relationships with the underlying SS and TSSJ were noted. The width and length of the PAM, and the distance between the muscle and reference points (asterion, mastoid tip, and midline), were measured. RESULTS: The PAM was identified in 18 sides (9 left, 9 right). The first 20 mm of the muscle length (mean 28.28 mm) consistently overlay the mastoid process anteriorly and the proximal half of the SS slightly posteriorly on all sides. The superior border was a mean of 2.22 mm inferior to the TSSJ and, especially when the muscle length exceeded 20 mm, this border extended closer to the transverse sinus; it was usually found at a mean of 3.11 mm (range 0.0-13.80 mm) inferior to the distal third of the transverse sinus. CONCLUSIONS: Superficial landmarks give surgeons improved surgical access, avoiding overexposure of deep neurovascular structures and reducing brain retraction. On the basis of our cadaveric study, the PAM is a reliable and accurate direct landmark for identifying the SS and TSSJ. The PAM could potentially be used for guiding the retrosigmoid approach.

Intrasellar Dermoid Cyst: Case Report of a Rare Lesion and Systematic Literature Review Comparing Intrasellar, Suprasellar, and Parasellar Locations.

OBJECTIVE: Intracranial dermoid cyst (DC) is a rare benign, slow-growing lesion, most commonly arising along the midline. They can occur in the supratentorial compartment, very rarely involve the sellar region and only exceptionally are intrasellar. The aim of our study is to address the challenges in the diagnosis and management of sellar DCs. METHODS: We performed a systematic review of sellar DCs, in keeping with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and described an intrasellar DC in a 32-year-old female who presented with bilateral blurring vision. RESULTS: The review identified 4 intrasellar, 29 suprasellar, and 28 parasellar cases. Intrasellar DCs more likely present with progressive visual impairment and pituitary hormone dysfunctions during the fifth decade of life. Suprasellar and parasellar DCs are typically diagnosed during the third decade of life because of diplopia, ptosis, trigeminal hypoaesthesia/para-esthesia or cyst's rupture. Sellar DCs are typically hypodense on computed tomography scans and contain calcifications. Magnetic resonance imaging features include T1 hyperintensity, T2 heterogeneous intensity, no restriction on diffusion-weighted images, and no contrast enhancement. Surgery is the treatment of choice. Gross total resection is achieved in 60% of intrasellar and 61.9% of suprasellar and parasellar DCs. Early postoperative complications are reported in 40.0%, 16.7%, and 23.8% of intrasellar, suprasellar, and parasellar DCs, respectively. CONCLUSIONS: Intrasellar DCs are rare lesions typically diagnosed later than suprasellar and parasellar DCs due to their different clinical presentations. However, they should be considered in the differential diagnosis of cystic lesions of the sella, including epidermoid cysts, craniopharyngiomas, Rathke's cleft cysts, and teratomas.

Clinical Impact and Predictors of Aneurysmal Rebleeding in Poor-Grade Subarachnoid Hemorrhage: Results From the National POGASH Registry.

BACKGROUND: Scarce data are available regarding rebleeding predictors in poor-grade aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVES: To investigate predictors and clinical impact of rebleeding in a national multicentric poor-grade aSAH. METHODS: Retrospective analysis of prospectively collected data from the multicentric Poor Grade Aneurysmal Subarachnoid Hemorrhage Study Group (POGASH) registry of consecutive patients treated from January 1, 2015, to June 30th, 2021. Grading was defined as pretreatment World Federation of Neurological Surgeons grading scale IV-V. Ultra-early vasospasm (UEV) was defined as luminal narrowing of intracranial arteries not due to intrinsic disease. Rebleeding was defined as clinical deterioration with evidence of increased hemorrhage on subsequent computed tomography scans, fresh blood from the external ventricular drain, or deterioration before neuroradiological evaluation. Outcome was assessed by the modified Rankin Scale. RESULTS: Among 443 consecutive World Federation of Neurological Surgeons grades IV-V patients with aSAH treated within a median of 5 (IQR 4-9) hours since onset, rebleeding occurred in 78 (17.6%). UEV (adjusted odds ratio [OR] 6.8, 95% CI 3.2-14.4; P < .001) and presence of dissecting aneurysm (adjusted OR 3.5, 95% CI 1.3-9.3; P = .011) independently predicted rebleeding while history of hypertension (adjusted OR 0.4, 95% CI 0.2-0.8; P = .011) independently reduced its chances. 143 (32.3) patients died during hospitalization. Rebleeding emerged, among others, as an independent predictor of intrahospital mortality (adjusted OR 2.2, 95% CI 1.2-4.1; P = .009). CONCLUSION: UEV and presence of dissecting aneurysms are the strongest predictors of aneurysmal rebleeding. Their presence should be carefully evaluated in the acute management of poor-grade aSAH.

Posterior Petrous Meningiomas: Surgical Classification and Postoperative Outcomes in a Case Series of 130 Patients Operated via the Retrosigmoid Approach.

OBJECTIVE: A standardized definition and classification of primary posterior petrous meningiomas (PPMs) is lacking, with consequent challenges in comparing different case series. This study aimed to provide an anatomical description and classification of PPMs analyzing a homogeneous series of patients operated via the retrosigmoid approach. METHODS: PPMs originate laterally to the petro-occipital fissure within the venous ring composed of the superior petrosal, sigmoid, inferior petrosal, and cavernous sinuses. We proposed a classification based on tumor site of origin, direction of growth relative to the internal acoustic meatus, and cranial nerves' displacement. Four types of PPMs were defined: retromeatal (type A), meatal (type B), premeatal (type C), and broad-based (type D). We performed a retrospective analysis of 130 consecutive patients with PPMs who underwent surgery as first-line treatment. RESULTS: The PPM classification predicted clinical presentation, postoperative morbidity, and resection rates. Headache, hydrocephalus, and cerebellar deficits were more common in type A (59.0%, 37.7%, 49.2%) and type D (66.7%, 66.7%, 33.3%). Hypoacusia/anacusia was more common in type B (87.5%), while trigeminal hypoesthesia/anesthesia was more common in type C (85.0%). After surgery, patients with type A and D PPMs were at higher risk to develop cerebellar deficits (11.5%-22.2%), whereas patients with type B and C PPMs presented with hypoacusia/anacusia (12.5%) and trigeminal deficits (10.0%), respectively. The near-total resection rate was higher in type A (91.8%), followed by types B (82.5%), C (80.0%), and D (77.8%) PPMs. CONCLUSIONS: The PPM surgical classification has an operative and prognostic relevance. In expert hands, the retrosigmoid approach represents a safe and effective approach to remove PPMs.

Transcortical endoportal subchoroidal endoscope-assisted approach to the third ventricle: from virtual reality to anatomical laboratory.

BACKGROUND: Surgical approaches to the third ventricle (TV) have always represented a technical challenge in neurosurgery. Virtual reality (VR) is attaining increasing relevance in training programs and preoperative planning. The aim of this study is to demonstrate the worthwhile mutual contribution of VR simulations and specimen dissections to develop a new surgical approach to the TV. METHODS: The transcortical endoportal subchoroidal endoscope assisted (TEPSEA) approach was planned and simulated thanks to VR (Surgical Theater©, LLC, Cleveland, OH, USA), and then implemented on cadaver specimens by using the VBAS portal system (Viewsite™ Brain Access System TC Model, Vycor Medical™ Inc., Boca Raton, FL, USA). We assessed anthropometric measurements during VR planning and evaluated surgical operability during anatomical dissections. RESULTS: Surgical field depths measured between 75.6 and 85.3 mm to mammillary bodies and habenular commissure, which were in mean 20.2 mm away. An 18-mm movement was estimated for 15°-posterior tilting of a 70-mm long VBAS. Excellent exposure and maneuverability were achieved within the TV through a 2.47 cm2 portal working area. The 30°-endoscope assistance expanded the access towards the anterior and posterior walls of the TV particularly to the infundibular recess, mammillary bodies, habenular commissure and pineal recess. CONCLUSIONS: We documented the utility of a step-by-step VR planning and simulation followed by anatomical dissections to study surgical approaches to deep brain areas. The TEPSEA exploits the portal system and endoscopic assistance to access the entire TV minimizing cortical and white matter manipulation.

Endoscopic sublabial transmaxillary approach to the inferior orbit: pearls and pitfalls-A comparative anatomical study.

OBJECTIVE: Although orbital surgery has always represented a challenge for neurosurgeons, keyhole and endoscopic techniques are gradually surging in popularity maximizing functional and esthetic outcomes. This quantitative anatomical study first compared the surgical operability achieved through three endoscopic approaches within the inferior orbit: the endoscopic sublabial transmaxillary (ESTMax), the endoscopic endonasal transethmoidal (EETEth), and the endoscope-assisted lateral orbitotomy (ELO). METHODS: Each of these approaches was performed bilaterally on five specimens. We described the ESTMax step-by-step, underlining its advantages and pitfalls in comparison with EETEth and ELO. Then, we assessed surgical measurements and operability in ESTMax, EETEth, and ELO. RESULTS: The ESTMax provided the most favorable operative window (278.9 ± 43.8 mm2; EETEth: 240.8 ± 21.5 mm2, p < 0.001; ELO: 263.1 ± 19.8 mm2, p = 0.006), the broadest surgical field area (415.9 ± 26.4 mm2; EETEth: 386.7 ± 30.1 mm2, p = 0.041; ELO: 305.2 ± 26.3 mm2, p < 0.001), surgical field depths significantly shorter than EETEth (p < 0.001) but similar to ELO, the widest surgical angles of attack (45°-65°; EETEth: 20°-30°, p < 0.001; ELO: 25°-50°, p < 0.001), and the greatest surgical mobility areas (EETEth: p < 0.001; ELO: p < 0.001). Furthermore, the ESTMax allowed multi-angled exposure and handy maneuverability around all the inferior intraorbital targets. Small anterior antrostomy, blunt intraorbital dissections, direct targets' approach, orbital floor reconstruction, and maxillary bone flap replacement may limit the ESTMax morbidity rates. CONCLUSIONS: The ESTMax is a minimally invasive "head-on" orbital approach that exploits endoscopic surgery advantages avoiding the cranio-orbital and trans-nasal approach limitations and possible complications. It represents a promising alternative to EETEth and ELO because of its optimal operability for resecting lesions extending into the entire inferior orbit.

Ectopic GH-secreting pituitary adenoma of the clivus: systematic literature review of a challenging tumour.

PURPOSE: Acromegaly is usually due to growth hormone (GH)-secreting pituitary adenomas, but it may be exceptionally caused by GH-secreting ectopic pituitary adenomas (EPA). EPA are defined as extra-sellar pituitary tumours, extra- or intra-cranially sited, entirely separated from the pituitary stalk and gland. The aim of the study is to address the challenges in the management of clival GHEPA. METHODS: We reported a case of a 53-year-old acromegalic patient with a primary clival GHEPA and reviewed systematically the relevant English literature between 1975 and 2019, in keeping with the PRISMA guidelines. RESULTS: Four cases of primary clival GHEPA have been described in literature apart from ours. All patients presented with acromegalic features, elevated circulating GH and/or insulin-like growth factor-1 levels. Hyperprolactinemia and empty sella were described in two cases, respectively. These tumours show the typical imaging characteristics of pituitary adenomas, but their neuroradiological diagnosis may be challenging due to their sizes and the difficulty in defining the absence of connections with the pituitary fossa. CONCLUSION: Although primary clival GHEPA are exceedingly rare, even if likely under-reported in literature, they should be considered in the differential diagnosis of clival tumours because of their specific management. Surgery represents the first-line treatment option, while medical and radiation therapies can be adopted as neo-adjuvant, adjuvant or primary treatments according to tumour and patient characteristics.

Cumulative intracranial tumour volume prognostic assessment: a new predicting score index for patients with brain metastases treated by stereotactic radiosurgery.

Brain metastases (BM) represent the most common intracranial malignancy in adults. Limitations of existing prognostic models reduce their predictivity and clinical applicability. The aim of this study is to validate the cumulative intracranial tumour volume prognostic assessment (CITVPA) as a new prognostic score system for patients with BM treated by Stereotactic Radiosurgery (SRS). Between January 2001 and December 2015, 1894 patients underwent Gamma Knife SRS treatment. The CITVPA model was implemented and validated as follows: the CITV cut-offs were identified thanks to a receiver-operating characteristic (ROC) curve analysis; the survival predictive factors were selected through a Cox proportional hazard model; its prognostic power was compared to RPA, SIR and GPA through the Harrel concordance index (HCI). According to the ROC curve analysis, the CITV cut-off values were set at 1.5 and 4.0 cc. Based on the multivariate analysis, the CITVPA model included: age (OR 1.010, 95% CI 1.005-1.015, p < 0.001), KPS (OR 0.960, 95% CI 0.956-0.965, p < 0.001), extracranial metastases (OR 1.287, 95% CI 1.154-1.437, p < 0.001), BM number (OR 1.193, 95% CI 1.047-1.360, p = 0.008), and CITV (OR 1.028, 95% CI 1.020-1.036, p < 0.001). A score between 0 and 1 was attributed to each prognosticator; a global CITVPA score ranging from 0 to 5 was assigned with higher results corresponding to worse outcomes. The CITVPA (HCI = 0.64) exhibited a significantly (p < 0.001) higher prognostic power compared to RPA (HCI = 0.55), SIR (HCI = 0.55) and GPA (HCI = 0.61). The CITVPA represents a reliable prognostic system for patients with BM treated by SRS. However, further prospective and multicentric studies are necessary before its applicability in clinical practice.

Mini Fronto-Orbital Approach: "Window Opening" Towards the Superomedial Orbit - A Virtual Reality-Planned Anatomic Study.

BACKGROUND: Surgical approaches to the orbit are challenging and require combined multispecialist skills. Considering its increasing relevance in neurosurgical practice, keyhole surgery could be also applied to this field. However, mastering a minimally invasive approach necessitates an extended learning curve. For this reason, virtual reality (VR) can be effectively used for planning and training in this demanding surgical technique. OBJECTIVE: To validate the mini fronto-orbital (mFO) approach to the superomedial orbit, using VR planning and specimen dissections, conjugating the principles of skull base and keyhole neurosurgery. METHODS: Three-dimensional measurements were performed thanks to Surgical Theater (Surgical Theater© LLC), and then, simulated craniotomies were implemented on cadaver specimens. RESULTS: The mFO approach affords optimal exposure and operability in the target area and reduced risks of surrounding normal tissue injuries. The eyebrow skin incision, the minimal soft-tissue retraction, the limited temporalis muscle dissection and the single-piece craniotomy, as planned with VR, are the key elements of this minimally invasive approach. Furthermore, the "window-opening" cotton-tip intraorbital dissection technique, based on widening surgical corridors between neuromuscular bundles, provides a safe orientation and a deep access inside the orbit, thereby significantly limiting the risk of jeopardizing neurovascular structures. CONCLUSION: The mFO approach associated to the window-opening dissection technique can be considered safe, effective, suitable, and convenient for treating lesions located in the superomedial orbital aspect, up to the orbital apex.

Uncertain Effectiveness of Prophylactic Anticonvulsive Medication in Predicting Cognitive Outcome of Neurosurgical Patients.

OBJECTIVES: To evaluate the influence of prophylactic anticonvulsive medication, above all levetiracetam monotherapy, in predicting the cognitive outcome of neurosurgical patients with post-traumatic brain injury, intracerebral hemorrhage, and encephalic tumors. METHODS: We examined data concerning 232 of 327 adult patients admitted to the Neurorehabilitation Department of the San Raffaele Hospital (Milan, Italy) after discharge from the Neurosurgery Department. Cognitive status was evaluated by means of the "Mini-Mental State" examination and the Functional Independence Measure at baseline and at the end of a rehabilitation care with an average duration of about four weeks. RESULTS: The vast majority of the patients were treated with levetiracetam. Our data showed a negative role of antiepileptic drugs on cognitive recovery in a cohort of neurosurgical patients. CONCLUSIONS: Knowing thoroughly the effects of antiepileptic drugs in rehabilitation outcome is of fundamental importance. This study represents the only large series analyzing these aspects in the rehabilitation of neurosurgical patients. Antiepileptic drugs should be managed to ensure patients the best possible cognitive outcome. Further evidence from good-quality trials is required to assess the clinical effectiveness of prophylactic anticonvulsive medication in predicting the cognitive outcome of neurosurgical patients who are treated with rehabilitation.

Health-care disparities stemming from sexual orientation of Italian patients with Multiple Sclerosis: A cross-sectional web-based study.

Lesbian, gay, bisexual and transgender (LGBT) patients might experience unique difficulties and barriers to treatment of chronic diseases related to their sexual orientation. Thus, we investigated concerns experienced by LGBT patients with multiple sclerosis (MS). We conducted a web-based survey using a multi-choice questionnaire published in an Italian social-network (www.smsocialnetwork.com) for MS patients. The survey investigated: socio-demographic factors, lifestyle habits, MS-related health status and LGBT specific issues (e.g. friendliness to their sexual orientation and eventual homophobic behaviors in the MS Center). Among MS patients willing to use psychological services, LGBT patients were associated with a smaller number of psychological consultations, compared to heterosexuals (Coeff.=-0.449; p<0.001; 95%CI=-0.682 to -0.217). LGBT patients were more likely to change MS Center, compared to heterosexuals (OR=2.064; p=0.046; 95%CI=1.011-4.212). The number of MS Center changes was associated with MS Center friendliness (p=0.037; rho=-0.229) and with the occurrence of homophobic behaviors (p=0.036; rho=0.234). LGBT MS patients more frequently changed MS Center and had a reduced use of psychological services, compared to heterosexuals. The attitude towards LGBT MS patients might affect resource utilizations and LGBTs health status.