Resection of supratentorial high-grade gliomas availing of neuronavigation matched intraoperative ultrasound and Fluorescein: How far is it safe to push the resection?

Background: High-Grade Gliomas are the most common primary brain malignancies and despite the multimodal treatment, and the increasing amount of adjuvant treatment options the overall prognosis remains dismal. The present investigation aims to analyze the safety profile of the use of intraoperative ultrasounds (Io-US) in a homogeneous and matched cohort of patients suffering from High-grade gliomas (HGG) operated on with or without the aid of Io-US and Fluorescein in specific relation to the incidence of neurological and functional status sequelae. Methods and materials: A retrospective analysis was performed on 74 patients affected by HGG. 22 patients were treated with Io-US matched with neuronavigational system (Group A); 15 patients were treated both with the use of Io-US and Fluorescein matched with neuronavigational system (Group B); 37 patients were treated with the use of the neuronavigational system only (Group C). Primary endpoints were the extent of resection and functional outcome (measured with Karnofski Performance Status). Results: Significative differences were observed in terms of a higher extent of resection in Group B. In a multivariate analysis, this data appears to be independent of the location (eloquent/non-eloquent) of the lesion and from its histology. Regarding functional outcomes, no differences were detected between the two groups. Conclusions: The present study is the first that analyzes the simultaneous use of Io-US and Fluorescein, and the results demonstrate that these two instruments together could improve the extent of resection in HGG while ensuring good outcomes in terms of functional status.

Idiopathic Normal Pressure Hydrocephalus: The Real Social and Economic Burden of a Possibly Enormous Underdiagnosis Problem.

Normal Pressure Hydrocephalus (iNPH) typically affects the elderly and can cause cognitive decline, resulting in its differential diagnosis with other neurodegenerative conditions. Moreover, it is probably underdiagnosed; such under- and misdiagnosis prevents the patient from receiving the right treatment and significantly affects the quality of life and life expectancy. This investigation is an in-depth analysis of the actual incidence of iNPH in the population of the province served by our hospital (circa 580,000 individuals). The first phase of this study was conducted by visualizing a total of 1232 brain CT scans performed in the Emergency Departments of the four hospitals of our network on patients who were admitted for different complaints yet screened as suspicious for iNPH. Subsequently, corresponding Emergency Department medical records were investigated to understand the medical history of each patient in search of elements attributable to an alteration of CSF dynamics. The cohort of positive CT scans, according to the radiological and clinical inclusion criteria, included 192 patients. Among the reasons to require acute medical care, "Fall" was the most common. The cumulative incidence of CT scans suggestive of iNPH among the patients undergoing CT scans was as high as 15.58%, and the period prevalence calculated for the total amount of patients accessing the Emergency Departments was 1.084%. The real incidence of iNPH in the population may be underestimated, and the social burden linked to the assistance of patients suffering from such untreated conditions could be significantly relieved.

Petroclival Clinoidal Folds and Arachnoidal Membranes of the Anteromedial Incisural Space: Clinical Anatomy for Neuro Critical Care.

A systematic and narrative literature review was performed, focusing attention on the anatomy of the area located at the junction of the sphenoid and the basal portion of the temporal bone (petrous bone, petrous apex, upper petro-clival region) encircled by the free edge of the tentorium, the insertion of the tentorium itself to the petrous apex and the anterior and posterior clinoid processes that give rise to three distinct dural folds or ligaments: the anterior petroclinoid ligament, the posterior petroclinoid ligament and the interclinoid ligament. These dural folds constitute the posterior portion of the roof of the cavernous sinus denominated "the oculomotor triangle". The main purpose of this review study was to describe this anatomical region, particularly in the light of the relationships between the anterior margin of the free edge of the tentorium and the above-mentioned components of the sphenoid and petrous bone.

Adult IDH Wild-Type Glioblastoma Ultrastructural Investigation Suggests a Possible Correlation between Morphological Biomarkers and Ki-67 Index.

Glioblastoma is an aggressive brain tumor with an average life expectancy between 14 and 16 months after diagnosis. The Ki-67 labeling index (LI), a measure of cellular proliferation, is emerging as a prognostic marker in GBM. In this study, we investigated the ultrastructure of glioblastoma tissue from 9 patients with the same molecular profile (adult IDH wild-type glioblastoma, wild-type ATRX, and positive for TP53 expression, GFAP expression, and EGFR overexpression) to find possible ultrastructural features to be used as biomarkers and correlated with the only parameter that differs among our samples, the Ki-67 LI. Our main results were the visualization of the anatomical basis of astrocyte-endothelial cells crosstalk; the ultrastructural in situ imaging of clusters of hyperactivated microglia cells (MsEVs); the ultrastructural in situ imaging of microglia cells storing lipid vesicles (MsLVs); the ultrastructural in situ imaging of neoplastic cells mitophagy (NCsM). The statistical analysis of our data indicated that MsEVs and MsLVs correlate with the Ki-67 LI value. We can thus assume they are good candidates to be considered morphological biomarkers correlating to Ki-67 LI. The role of NCsM instead must be further evaluated. Our study findings demonstrate that by combining ultrastructural characteristics with molecular information, we can discover biomarkers that have the potential to enhance diagnostic precision, aid in treatment decision-making, identify targets for therapy, and enable personalized treatment plans tailored to each patient. However, further research with larger sample sizes is needed to validate these findings and fully utilize the potential of ultrastructural analysis in managing glioblastoma.

EGFR-Driven Mutation in Non-Small-Cell Lung Cancer (NSCLC) Influences the Features and Outcome of Brain Metastases.

Background: Brain metastases (BMs) is one of the most frequent metastatic sites for non-small-cell lung cancer (NSCLC). It is a matter of debate whether EGFR mutation in the primary tumor may be a marker for the disease course, prognosis, and diagnostic imaging of BMs, comparable to that described for primary brain tumors, such as glioblastoma (GB). This issue was investigated in the present research manuscript. Methods: We performed a retrospective study to identify the relevance of EGFR mutations and prognostic factors for diagnostic imaging, survival, and disease course within a cohort of patients affected by NSCLC-BMs. Imaging was carried out using MRI at various time intervals. The disease course was assessed using a neurological exam carried out at three-month intervals. The survival was expressed from surgical intervention. Results: The patient cohort consisted of 81 patients. The overall survival of the cohort was 15 ± 1.7 months. EGFR mutation and ALK expression did not differ significantly for age, gender, and gross morphology of the BM. Contrariwise, the EGFR mutation was significantly associated with MRI concerning the occurrence of greater tumor (22.38 ± 21.35 cm3 versus 7.68 ± 6.44 cm3, p = 0.046) and edema volume (72.44 ± 60.71 cm3 versus 31.92 cm3, p = 0.028). In turn, the occurrence of MRI abnormalities was related to neurological symptoms assessed using the Karnofsky performance status and mostly depended on tumor-related edema (p = 0.048). However, the highest significant correlation was observed between EGFR mutation and the occurrence of seizures as the clinical onset of the neoplasm (p = 0.004). Conclusions: The presence of EGFR mutations significantly correlates with greater edema and mostly a higher seizure incidence of BMs from NSCLC. In contrast, EGFR mutations do not affect the patient's survival, the disease course, and focal neurological symptoms but seizures. This contrasts with the significance of EGFR in the course and prognosis of the primary tumor (NSCLC).

Role of 1p/19q Codeletion in Diffuse Low-grade Glioma Tumour Prognosis.

BACKGROUND/AIM: In the latest 2021 WHO classification of central nervous system tumours (CNS), gliomas that present isocitrate dehydrogenase (IDH) mutations are defined as diffuse low-grade gliomas (DLGGs). IDH mutations are commonly observed in this tumour type. The Extent of Resection (EOR) positively influence survival; however, it is still debated whether the predictive value of EOR is independent of the 1p/19q co-deletion. We carried out a retrospective analysis on patients operated on for DLGG at the Sant'Andrea University Hospital Sapienza University of Rome, correlating the outcome with the presence of 1p/19q co-deletion and EOR. PATIENTS AND METHODS: The study examined 66 patients with DLGG who had undergone surgery for tumour resection between 2008 and 2018. Patients with DLGG were divided into two groups; diffuse astrocytoma (DA) in which 1p/19q codeletion is absent and oligodendroglioma (OG) in which 1p/19q codeletion is present. According to EOR, both groups were divided into two subgroups: subtotal resection (STR) and gross total resection (GTR). Three end-point variables were considered: overall survival (OS), progression-free survival (PFS) and time to malignant transformation (TMT). RESULTS: In the DA group, the GTR subgroup had an average OS of 81.6 months, an average PFS of 45.9 months and an average TMT of 63.6 months. After surgery, these patients had an average Karnofsky Performance Score (KPS) of 83.4. The STR subgroup had an average OS of 60.4 months, PFS was 38.7 months, and TMT was 46.4 months, post-operative KPS was 83.4. In contrast, in the OG group, the GTR averagely had 101.7 months of OS, 64.9 months of PFS, 80.3 months of TMT and an average post-operative KPS of 84.2, and the STR subgroup had an average of OS of 73.3 months, PFS of 48.2 months, TMT of 57.3 and an average postoperative KPS of 96.2. CONCLUSION: In patients affected by DLGGs, 1p/19q codeletion is significantly associated with prolonged survival and longer time-to-malignant transformation (TMT) compared to the absence of 1p/19q codeletion. Also, the extent of surgical resection (EOR) in DLGG patients has been confirmed as one of the main prognostic factors. However, its predictive value is substantially influenced by the presence of the 1p/19q codeletion.

Clinical Efficacy of Adjuvant Radiotherapy for World Health Organization Grade II Intracranial Meningioma.

BACKGROUND: Maximal surgical resection remains the treatment of choice for grade II meningiomas, and for some authors it is sufficient to guarantee a long indolent course even without postsurgical radiotherapy (RT), but there is no consensus on the use of RT in this patient population. METHODS: We retrospectively compared clinical and radiologic outcomes between World Health Organization grade I (group A) and grade II (group B) surgically treated meningiomas, focusing on the role of adjuvant RT. We registered clinical, surgical, and radiologic data to detect differences in survival and functional outcome between the 2 groups. RESULTS: The final cohort consisted of 284 patients for group A and 94 patients for group B. Group B showed a higher risk of developing recurrence independently of the extent of resection (7.75% for Group A vs. 27.7% for Group B, P = 0.01). Patients who did not undergo adjuvant RT documented recurrence in 50% of cases, compared with 19% of patients who underwent RT (P = 0.024). There is a weak difference in the risk of developing postoperative seizures in the group submitted to radiotherapy (P = 0.08). Performance status remained stable for both groups, but for Group B it tended to decrease significantly after 1 year with regard to extent of resection and RT. CONCLUSIONS: Recurrence is more frequent for grade II meningiomas, even though there are no significant differences in terms of complications and functional outcome. Radiotherapy in grade II meningiomas does indeed lead to better control of recurrence but leads to an increased risk of seizures and reduced performance status.

Development of a Novel Device for Decompressive Craniectomy: An Experimental and Cadaveric Study and Preliminary Clinical Application.

BACKGROUND: Decompressive craniectomy is an intervention of established efficacy in patients with intractable cerebral edema. OBJECTIVE: To evaluate a new device used in alternative to decompressive craniectomy. This device is designed to perform an augmentative craniotomy by keeping the bone flap elevated using specific cranial suspension titanium plates and giving the brain enough room to swell. METHODS: We tested the mechanical characteristics of the cranial brackets on dried skulls, on 3D-printed skull models, and on a preserved cadaver head. The resistance of the device was examined through dynamometric testing, and the feasibility of the surgical technique, including the suspension of the bone flap and the skin closure, was investigated on the cadaveric model. A preliminary clinical series of 2 patients is also reported. RESULTS: The laboratory tests have shown that this system allows an adequate expansion of the intracranial volume and it could withstand a force up to 637 ± 13 N in the synthetic model and up to 658 ± 9 N in the human skull without dislocation or failure of the brackets nor fractures of the bone ridges. Preliminary application in the clinical setting has shown that augmentative craniotomy is effective in the control of intracranial hypertension and could reduce the costs and complications associated with the classical decompressive craniectomy technique. CONCLUSION: Preliminary laboratory and clinical results show augmentative craniotomy to be a promising, alternative technique to decompressive craniectomy. Further clinical studies will be needed to validate its efficacy.

Extradural Clinoidectomy in Clinoidal Meningiomas: Analysis of the Surgical Technique and Evaluation of the Clinical Outcome.

The surgical treatment of clinoidal meningiomas is currently still discussed in the literature. Different surgical approaches have been proposed and evaluated, in multiple studies, in order to improve the surgical outcomes. The aim of this study is to evaluate the advantages of extradural clinoidectomy in the context of tumor removal radicality for visual function improvement. A retrospective analysis was performed on 74 patients-of which 26 patients with clinoidal meningiomas were in group III, according to Al Mefty classification-who underwent surgery at the Policlinico Umberto I Hospital between 2000 and 2019. Further, extradural clinoidectomy was performed on 15 patients (Group A), and 11 patients underwent the pterional approach only (Group B). Additionally, visual impairment was present in all 26 patients before surgery. Next, visual function assessment was performed on all patients, both in presurgery and postsurgery. Radiological follow up was performed at 3 and 6 months, and then every 12 months. Gross Total Resection (GTR) was achieved in 13/15 (86.7%) patients who underwent clinoidectomy, and in 4/11 (36.4%) patients who did not undergo clinoidectomy. Visual function improvement was achieved in 12/15 (80%) patients who underwent clinoidectomy and in 4 of 11 (36.4%) who did not undergo clinoidectomy. According to our study, extradural clinoidectomy is the most suitable method for facilitating the gross total resection of clinoidal meningiomas. Our experience and data suggest that a higher rate of total resection and, subsequently, the best visual outcomes are achieved. Extradural drilling via the anterior clinoid process reveals a wider surgical corridor for meticulous tumor resection.

Full-Thickness Craniodural Metastasis with Leptomeningeal Infiltration of Salivary Origin: A Radiological Lesson and a Technical Remark.

Calvarial metastases are a relatively rare entity, with an overall incidence of 3-4%. Among these cases, metastases arising from salivary gland cancers are even rarer; in fact, large studies regarding salivary gland tumors showed that brain metastases are observed in 0.8% of the cases. Generally, bone metastases have been described in proximity to primary tumors, while bloodstream-disseminated lesions are often located inside the brain parenchyma. During every surgical step, traction on lower-lying infiltrated tissues must be avoided in order to successfully remove the lesion. This case report presents the first ever case of a 67-year-old woman affected by submandibular gland undifferentiated adenocarcinoma metastasis with a full-thickness involvement of the calvarium, pachy- and leptomeninges.

Global Neurocognitive and Frontal Functions Analysis and Precision Intrathecal Pressure Measurement to Settle the Diagnostic Dilemma of the Normal Pressure Hydrocephalus: A Preliminary Experience.

INTRODUCTION: Normal-pressure hydrocephalus (NPH) is a common condition associated with a cognitive deterioration and possibly involving up to 9%-14% of all nursing home residents older than 65 years old. The purpose of the present paper is to introduce an inclusive study protocol aimed at increasing the diagnostic precision and follow-up accuracy. METHODS: A total of 28 patients were operated on for NPH in our institution in the period ranging between January 2015 and December 2019. All the patients underwent magnetic resonance imaging of the brain with standard sequences, calculation of the Evans index and corpus callosum angle, and evaluations by means of Montreal Cognitive Assessment (MOCA), Mini-Mental State Examination, and Frontal Assessment Battery (FAB) neuropsychological tests preoperatively and at 1 and 6 months. A preoperative lumbar test infusion (LIT) with fine measurement of the intrathecal pressures at the beginning and at the end of the procedures was performed. RESULTS: MOCA and FAB proved an overall improvement of the neurocognitive conditions at 1 month postoperatively. The mean pressure at the beginning of the LIT, was negatively associated with the neuropsychological outcome variables (Mini-Mental State Examination, FAB, and MOCA) in the 3 different evaluations, with FAB and MOCA at 6 months. We found a strong positive correlation between the Evans index as measured on the first magnetic resonance imaging scan both with the diastolic and systolic pressure at the beginning of the test. CONCLUSIONS: Neuropsychological assessment, combined with LIT with intrathecal pressure managements aids the diagnostic process in patients affected by NPH. It allows standardizing in a rigorous fashion the follow-up evaluation of patients undergoing surgery for a ventriculoperitoneal shunt.

The Surgical Risk Factors of Giant Intracranial Meningiomas: A Multi-Centric Retrospective Analysis of Large Case Serie.

Giant intracranial meningiomas (GIMs) are a subgroup of meningiomas with huge dimensions with a maximum diameter of more than 5 cm. The mechanisms by which a meningioma can grow to be defined as a "giant" are unknown, and the biological, radiological profile and the different outcomes are poorly investigated. We performed a multi-centric retrospective study of a series of surgically treated patients suffering from intracranial meningioma. All the patients were assigned on the grounds of the preoperative imaging to giant and medium/large meningioma groups with a cut-off of 5 cm. We investigated whether the presence of large diameter and peritumoral brain edema (PBE) on radiological diagnosis indicates different mortality rates, grading, characteristics, and outcomes in a multi-variate analysis. We found a higher risk of developing complications for GIMs (29.9% versus 14.8%; p < 0.01). The direct proportional relationship between PBE volume and tumor volume was present only in the medium/large group (Pearson correlation with p < 0.01) and not in the GIM group (p = 0.47). In conclusion, GIMs have a higher risk of developing complications in the postoperative phase than medium/large meningioma without higher risk of mortality and recurrence.

Intracranial Meningioma in Elderly Patients. Retrospective Multicentric Risk and Surgical Factors Study of Morbidity and Mortality.

With the increasing life expectancy, a large number of intracranial meningiomas (IM) have been identified in elderly patients. There is no general consensus regarding the management for IMs nor studies regarding the outcome of older patients undergoing meningioma surgery. We aimed to determine whether preoperative variables and postoperative clinical outcomes differ between age groups after meningioma surgery. We analyzed data from all patients who had undergone IM surgery from our departments. The final cohort consisted of 340 patients affected by IM with ASA class I-II: 188 in the young group (<65) and 152 in the elderly. The two subgroups did not present significant differences concerning biological characteristics of tumor, localization, diameters, lesion and edema volumes and surgical radicality. Despite these comparable data, elderly presented with a significantly lower Karnofsky Performance status value on admission and remained consistently lower during the follow-up. We establish instead that there is no intrinsic correlation to the presence of IM and no significant increased risk of complications or recurrence in elderly patients, but rather only an increased risk of reduced performance status with mortality related to the comorbidity of the patient, primarily cardiovascular disease, and an intrinsic frailty of the aged population.

Sacral Nerves Reconstruction After Surgical Resection of a Large Sacral Chordoma Restores the Urinary and Sexual Function and the Anal Continence.

OBJECTIVE: Chordomas are slow-growing tumors, with a high tendency to local relapse. En bloc resection is related to the most favorable outcome in terms of survival but is frequently associated with permanent neurological deficits involving sphincters and sexual functions. In the present article, we describe an innovative technique of en bloc resection followed by reconstruction of the sacral nerves with nerve grafts. METHODS: The chordoma was excised through a posterior approach after dividing the proximal and distal sacral nerves using the established technique. After that, a microsurgical S2-S3-S4 nerve reconstruction was performed connecting the proximal and distal stumps with sural nerve grafts withdrawn from both lower limbs. RESULTS: Immediately after surgery, the patient experienced complete impairment of sexual function and sphincters with urinary and fecal incontinence. After 6 months, there was a progressive recovery of sexual function and sphincter control. One year after the operation, the patient achieved an adequate sexual life (erection and ejaculation) and complete control of the bladder and anal sphincter. CONCLUSION: Reconstruction of nerves sacrificed during sacral tumor removal has been shown to be effective in restoring sphincter and sexual function and is a promising technique that may significantly improve patients' quality of life.

Post-traumatic intracranial pseudo-aneurysms of posterior circulation: a comprehensive review of an under-diagnosed and rare entity.

Traumatic aneurysms are rare and the total number of cases involving the posterior circulation (TIPC) is even smaller. Traumatic brain injury (TBI) may be responsible not only of rupture in brain aneurysm (BrA) pre-existing to trauma, but it has been identified also as a possible pathogenetic cause of TIPC formation in patients not affected by intracranial vascular lesions. A complete literature review was performed of all reported cases regarding rupture of BrA with SAH resulting from TIPC not previously identified at the first radiological screening. A representative case of a left posterior inferior cerebellar artery (PICA) pseudo-aneurysm caused by left vertebral artery's dissection is reported. We show a unique complete collection of all 34 cases. Despite their rarity, TIPCs are associated with a significant morbidity and mortality rate, as high as 40-60%. Of the 22 patients with good neurological status (64.7%), we did not notice a significant correlation with regard to the location of the aneurysm, type of treatment, or clinical onset. Early recognition of a pseudo-aneurysm and adequate treatment seem to be the most important prognostic factor for these patients. Despite their rarity, TIPCs are associated with a significant morbidity and mortality rate. A TIPC should be suspected in case of delayed deterioration in head-injured patient and should be investigated with angiography. Conservative management is worsened by poor prognosis and the goal of treatment is to exclude the aneurysm from circulation with surgical or endovascular methods as soon as possible.

Ultrasound Lancet-aided Translaminar Posterior Lumbar Approach to the Recesso-Foraminal Area: Technical Note.

Extrusion and sequestration of the nucleus pulposus involving the spinal canal or the foramina/recesses complicates up to 28% of the lumbar disc herniations. The transpars/translaminar anatomical approach is well described and its advantages when handling with a lateral, foraminal extruded disc herniation are appreciated and recognized. Nevertheless, this approach presents several pitfalls such as the risk of disconnecting the pars interarticularis, which may cause segmental instability. This particular eventuality is because of the particular anatomical conformation of the pars interarticularis. Although already part of the modern surgical armamentarium for general, orthopedic, cranial and spinal surgeons, the use of the ultrasonic scalpel technique for such approach has never been discussed to date, to the best of our knowledge. The purpose of the present paper is therefore to introduce and describe the stepwise technique along with an extensive discussion of the facilitating role of the ultrasonic scalpel in the translaminar/transpars approach in the management of extruded disc herniation of the lumbar spine.

IDH Wild-type Glioblastoma Presenting with Seizure: Clinical Specificity, and Oncologic and Surgical Outcomes.

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain neoplasia in adults. Seizure is a common manifestation in GBM. Up to 25 to 60% of patients with GBM have seizures. We aim to summarize all the relevant clinical, surgical, radiologic, and molecular features of a cohort of patients suffering from GBM-related epilepsy and measure the outcome, to understand the possible existence of a clinical/phenotypical specificity of this subgroup of patients. METHODS: We retrospectively analyzed a cohort of 177 patients affected by isocitrate dehydrogenase wild-type (IDH-WT) GBM; 49 patients presented seizure at onset (SaO) and 128 were seizure free (SF). We investigated the relationship between seizures and other prognostic factors of GBMs. RESULTS: A statistically significant association between the location of the lesions in the parietal lobe and seizures was observed. The left side was more commonly affected. Interestingly, there was a statistical relationship between tumors involving the subventricular zone (SVZ) and SaO patients. The tumors were also smaller on average at diagnosis, and generalized SaOs were associated with longer overall survival. CONCLUSIONS: The typical patient with IDH-WT GBM with SaO is a young (<55 year) male without a history of headache. The lesion is typically small to medium in size and located in the temporoparietal dominant lobe, with a high tendency to involve the SVZ.

Diffuse Axonal Injury: Clinical Prognostic Factors, Molecular Experimental Models and the Impact of the Trauma Related Oxidative Stress. An Extensive Review Concerning Milestones and Advances.

Traumatic brain injury (TBI) is a condition burdened by an extremely high rate of morbidity and mortality and can result in an overall disability rate as high as 50% in affected individuals. Therefore, the importance of identifying clinical prognostic factors for diffuse axonal injury (DAI) in (TBI) is commonly recognized as critical. The aim of the present review paper is to evaluate the most recent contributions from the relevant literature in order to understand how each single prognostic factor determinates the severity of the clinical syndrome associated with DAI. The main clinical factors with an important impact on prognosis in case of DAI are glycemia, early GCS, the peripheral oxygen saturation, blood pressure, and time to recover consciousness. In addition, the severity of the lesion, classified on the ground of the cerebral anatomical structures involved after the trauma, has a strong correlation with survival after DAI. In conclusion, modern findings concerning the role of reactive oxygen species (ROS) and oxidative stress in DAI suggest that biomarkers such as GFAP, pNF-H, NF-L, microtubule associated protein tau, Aß42, S-100ß, NSE, AQP4, Drp-1, and NCX represent a possible critical target for future pharmaceutical treatments to prevent the damages caused by DAI.