Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma.

Immunosuppressive macrophages restrict anti-cancer immunity in glioblastoma (GBM). Here, we studied the contribution of microglia (MGs) and monocyte-derived macrophages (MDMs) to immunosuppression and mechanisms underlying their regulatory function. MDMs outnumbered MGs at late tumor stages and suppressed T cell activity. Molecular and functional analysis identified a population of glycolytic MDM expressing GLUT1 with potent immunosuppressive activity. GBM-derived factors promoted high glycolysis, lactate, and interleukin-10 (IL-10) production in MDMs. Inhibition of glycolysis or lactate production in MDMs impaired IL-10 expression and T cell suppression. Mechanistically, intracellular lactate-driven histone lactylation promoted IL-10 expression, which was required to suppress T cell activity. GLUT1 expression on MDMs was induced downstream of tumor-derived factors that activated the PERK-ATF4 axis. PERK deletion in MDM abrogated histone lactylation, led to the accumulation of intratumoral T cells and tumor growth delay, and, in combination with immunotherapy, blocked GBM progression. Thus, PERK-driven glucose metabolism promotes MDM immunosuppressive activity via histone lactylation.

Treatment of giant intracranial aneurysms: long-term outcomes in surgical versus endovascular management.

Aneurysms with a major diameter > 25 mm are defined as giant intracranial aneurysms (GIAs). Different clinical, pathological, and radiological factors were revealed as playing a role in choosing the best strategy between surgical and endovascular approaches. Despite the improvement of both techniques, the efficacy and safety of these different management are still debated. We evaluated the differences in clinical and radiological outcomes of GIAs treated with surgical and endovascular techniques in a large retrospective mono-centric study. We compared aneurysm location, clinical, morphological features, treatment outcome, and complications on the ground of treatment technique. The final cohort consisted of 162 patients. All the patients were assigned on the ground of the type of eligible treatment: surgical (118 patients) and endovascular procedure (44 patients). The different treatment strategies were made through a multidisciplinary selection whereas clinical parameters, location, and morphologic features of the aneurysm were considered. The surgical group manifested a greater reduction in performance levels and neurological status in the post-operative phases than the endovascular group (p < 0.01) with a higher incidence of complications (p = 0.012) in contrast to a lower recurrence rate (p > 0.01). There is no significant difference in post-operative mortality and survival between surgical and endovascular groups. The surgical group manifested a higher incidence of complications after treatment. The endovascular group has a better post-operative outcome, but a higher risk of recurrence and the necessity of further treatment.

Glycan-Lectin Interactions as Novel Immunosuppression Drivers in Glioblastoma.

Despite diagnostic and therapeutic improvements, glioblastoma (GB) remains one of the most threatening brain tumor in adults, underlining the urgent need of new therapeutic targets. Lectins are glycan-binding proteins that regulate several biological processes through the recognition of specific sugar motifs. Lectins and their ligands are found on immune cells, endothelial cells and, also, tumor cells, pointing out a strong correlation among immunity, tumor microenvironment and vascularization. In GB, altered glycans and lectins contribute to tumor progression and immune evasion, shaping the tumor-immune landscape promoting immunosuppressive cell subsets, such as myeloid-derived suppressor cells (MDSCs) and M2-macrophages, and affecting immunoeffector populations, such as CD8+ T cells and dendritic cells (DCs). Here, we discuss the latest knowledge on the immune cells, immune related lectin receptors (C-type lectins, Siglecs, galectins) and changes in glycosylation that are involved in immunosuppressive mechanisms in GB, highlighting their interest as possible novel therapeutical targets.

Proteomic study of pilocytic astrocytoma pediatric brain tumor intracystic fluid.

Liquid chromatography in coupling with high-resolution ESI-LTQ-Orbitrap mass spectrometry was applied for a proteomic study of pediatric pilocytic astrocytoma brain tumor intracystic fluid by an integrated top-down/bottom-up platform. Both of the proteomic strategies resulted complementary and support each other in contributing to a wide characterization of the protein and peptide content of the tumor fluid. Top-down approach allowed to identify several proteins and peptides involved in different biological activities together with the characterization of interesting proteoforms such as fibrinopeptide A and its truncated form, fibrinopeptide B, complement C3f fragments, ß-thymosin peptides, ubiquitin, several apolipoproteins belonging to A and C families, apolipoprotein J and D, and cystatin C. Of particular interest resulted the identification of a N-terminal truncated cystatin C proteoform, likely involved in immune response mechanism modulations and the identification of oxidized and glycosylated apolipoproteins including disulfide bridge dimeric forms. The bottom-up approach confirmed some of the experimental data findings together with adding the characterization of high-molecular-mass proteins in the samples. These data could contribute to elucidate the molecular mechanisms involved in onset and progression of the disease and cyst development.

Proteomic characterization of pediatric craniopharyngioma intracystic fluid by LC-MS top-down/bottom-up integrated approaches.

The combination of top-down and bottom-up platforms was utilized for the LC-MS proteomic characterization of the intracystic fluid of adamantinomatous craniopharyngioma pediatric brain tumor disease. Proteins and peptides characterization was achieved by high-resolution LC-ESI-LTQ-Orbitrap-MS analysis while low-resolution LC-ESI-IT-MS was applied for the complete screening of the samples and the evaluation of the protein distribution within patients. Top-down analyses were applied to liquid/liquid extracted samples while bottom-up analyses were performed after trypsin digestion of both untreated and pretreated samples. The two proteomic approaches were complementary for the characterization of the proteome of craniopharyngioma intracystic fluid. Proteins and peptides involved in inflammation, mineralization processes and lipid transport were identified, in agreement with the calcium flecks, cholesterol granules and bone residues characteristic of this fluid. Apolipoprotein A-I, A-II, C-I and J, hemoglobin fragments, ubiquitin, α-2-HS-glycoprotein or fetuin A, α-1-antichymotrypsin, vitamin D binding protein, and α-1-acid glycoprotein were characterized. These data could be relevant for the comprehension of the processes involved in the pathogenesis of the disease and the development of the cyst and could contribute to the individuation of therapeutic targets for the reduction of the cyst volume delaying and/or avoiding invasive surgical treatments.

The Impact of the COVID-19 Pandemic and Lockdown on the Outcome of Glioblastoma.

BACKGROUND: Rapid spread of the SARS-CoV-2 pandemic in 2020 led to an indirect effect on non-COVID patients. Since neuro-oncology cases are unique and brain tumors need a specific therapeutic protocol at proper doses and at the right times, the effects of the pandemic on health care services for patients with glioblastomas (GBs) and their impact on overall survival (OS) and quality of life are not yet known. METHODS: We conducted a retrospective study of 142 GB patients who underwent surgery, radiation, and chemotherapy before and after the lockdown period, aiming to determine the differences in access to care, treatment modality, and adjuvant therapies, and how the lockdown changed the prognosis. RESULTS: The number of procedures performed for GB during the pandemic was comparable to that of the prepandemic period, and patients received standard care. There was a significant difference in the volume of lesions measured at diagnosis with a decreased number of "accidental" diagnoses and expression of a reduced use by the patient for a checkup or follow-up examinations. Patients expressed a significantly lower performance index in the lockdown period with longer progression-free survival (PFS) in the face of a comparable mean time to OS. CONCLUSION: Patients treated surgically for GB during the pandemic period had a more pronounced and earlier reduction in performance status than patients treated during the same period the year before. This appears to be primarily due to lower levels of care in the rehabilitation centers and more frequent discontinuation of adjuvant care.

Predicting in-hospital mortality in patients admitted from the emergency department for pulmonary embolism: Incidence and prognostic value of deep vein thrombosis. A retrospective study.

BACKGROUND: Pulmonary embolism (PE) is one of the most common causes of death from cardiovascular disease. Although deep vein thrombosis (DVT) is the leading cause of PE, its prognostic role is unclear. This study investigated the incidence and prognostic value of DVT in predicting in-hospital mortality (IHM) in patients admitted from the emergency department (ED) for PE. METHODS: This retrospective cohort study was conducted in the ED of a third-level university hospital. Patients over 18 years admitted for PE between 1 January 2018 and 31 December 2022 were included. RESULTS: Five hundred and thirty patients (mean age 73.13 years, 6% IHM) were included. 69.1% of cases had DVT (36.4% unilateral femoral vein, 3.6% bilateral, 39.1% unilateral popliteal vein, 2.8% bilateral, 45.7% distal vein thrombosis and 7.4% iliocaval involvement). Patients who died in hospital had a higher Pulmonary Embolism Severity Index (PESI) (138.6 vs. 99.65, p < 0.001), European Society of Cardiology risk class (15.6% vs. 1%, intermediate-high in 50% vs. 6.4%, p < 0.001) and more DVT involving the iliac-caval vein axis (18.8% vs. 6.6%, p = 0.011). PESI class >II, right ventricular dysfunction, increased blood markers of myocardial damage and involvement of the iliocaval venous axis were independent predictors of IHM on multivariate analysis. CONCLUSIONS: Although further studies are needed to confirm the prognostic role of DVT at PE, involvement of the iliocaval venous axis should considered to be a sign of a higher risk of IHM and may be a key factor in prognostic stratification.

The role of echocardiography in pulmonary embolism for the prediction of in-hospital mortality: a retrospective study.

PURPOSE: Pulmonary Embolism (PE) is the third leading cause of cardiovascular death, following myocardial infarction and stroke. The latest European Society of Cardiology (ESC) guidelines on PE recommend short-term prognostic stratification based on right ventricular (RV) overload detected by transthoracic echocardiography (TTE) or contrast-enhanced chest CT. The aim of the study is to find out which of the signs of right ventricular dysfunction best predicts in-hospital mortality (IHM). METHODS: This is a monocentric, retrospective study including adult patients admitted from the emergency department with a c-e cCT confirmed diagnosis of PE between January 2018 and December 2022 who underwent a TTE within 48 h. RESULTS: 509 patients (median age 76 years [IQR 67-84]) were included, with 7.1% IHM. At univariate analysis, RV/LV ratio > 1 (OR 2.23, 95% CI 1.1-4.5), TAPSE < 17 mm (OR 4.73, 95% CI 2.3-9.8), the D-shape (OR 3.73, 95% CI 1.71-8.14), and LVEF < 35% (OR 5.78, 95% CI 1.72-19.47) resulted significantly correlated with IHM. However, at multivariate analysis including also haemodynamic instability, PESI class > II, and abnormal hs-cTnI levels, only LVEF < 35% (OR 5.46, 95% CI 1.32-22.61) resulted an independent predictor of IHM. CONCLUSION: Despite the recognised role of TTE in the early management of patients with circulatory shock and suspected PE, signs of RV dysfunction have been shown to be poor predictors of IHM, whereas severely reduced LVEF is an independent risk factor for in-hospital death.

Aerosol corrosion prevention and energy-saving strategies in the design of green data centers.

The energy demands of data centers (DCs) worldwide are rapidly increasing, as are their environmental and economic costs. This paper presents a study conducted at Sannazzaro de' Burgondi (Po Valley), Italy, specifically aimed at optimizing the operating conditions of a DC designed for the Italian Oil and Gas Company (Eni) (5200 m(2) of Information Technology installed, 30 MW) and based on a direct free cooling (DFC) system. The aim of the study was to save the largest possible quantity of energy, while at the same time preventing aerosol corrosion. The aerosol properties (number size distribution, chemical composition, deliquescence relative humidity (DRH), acidity) and meteorological parameters were monitored and utilized to determine the potential levels of aerosol entering the DC (equivalent ISO class), together with its DRH. These data enabled us both to select the DC's filtering system (MERV13 filters) and to optimize the cooling cycle through calculation of the most reliable humidity cycle (60% of maximum allowed RH) applicable to the DFC. A potential energy saving of 81%, compared to a traditional air conditioning cooling system, was estimated: in one year, for 1 kW of installed information technology, the estimated energy saving is 7.4 MWh, resulting in 2.7 fewer tons of CO2 being emitted, and a financial saving of € 1100.

Identification of thymosins ß4 and ß 10 in paediatric craniopharyngioma cystic fluid.

BACKGROUND: Adamantinomatous craniopharyngioma is the third most recurrent paediatric brain tumour. Although histologically benign, it behaves aggressively as a malignant tumour due to invasion of the hypothalamus and visual pathways. Surgery is still the first and almost the only mode of treatment, although serious damage can occur as a consequence of tumour localization. The proteomic characterization of the intracystic tumoural fluid could contribute to the comprehension of the tumorigenesis processes and to the development of therapeutic targets to reduce cyst volume, allowing less invasive surgery and/or delay of the radical resection of the tumour mass and the collateral serious effects. METHODS: Intracystic fluid was analysed by a LC-ESI-IT-MS top-down platform after acidification, deproteinization and chloroform liquid/liquid extraction. FINDINGS: Thymosin ß4 and ß10 peptides were for the first time identified in the intracystic fluid of adamantinomatous craniopharyngioma by low- and high-resolution MS analysis coupled with LC. The two peptides showed the same distribution trend in the analysed samples. Thymosin ß4 and ß10 were present in 77 % of the analysed samples. These peptides were not found in the cerebrospinal fluid available for two patients. INTERPRETATION: The presence of ß-thymosins in the intracystic fluid of the tumour confirmed the secretion of these proteins in the extracellular environment. Due to their G-actin-sequestering activity and antiapoptotic and anti-inflammatory properties, these peptides could be strictly involved in both tumour progression and cyst development and growth.

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.

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.

Predicting in-hospital mortality in pulmonary embolism patients: development and external validation of the PATHOS score.

OBJECTIVE: According to the 2019 European Society of Cardiology (ESC) guidelines on pulmonary embolism (PE), prognosis is calculated using the Pulmonary Embolism Severity Index (PESI), a complex score with debated validity, or simplified PESI (sPESI). We have developed and validated a new risk score for in-hospital mortality (IHM) of patients with PE in the emergency department. METHODS: This retrospective, dual-center cohort study was conducted in the emergency departments of two third-level university hospitals. Patients aged >18 years with a contrast-enhanced computed tomography-confirmed PE were included. Clinical variables and laboratory tests were evaluated blindly to IHM. Multivariable logistic regression was performed to identify the new score's predictors, and the new score was compared with the PESI, sPESI, and shock index. RESULTS: A total of 1,358 patients were included in this study: 586 in the derivation cohort and 772 in the validation cohort, with a global 10.6% of IHM. The PATHOS scores were developed using independent variables to predict mortality: platelet count, age, troponin, heart rate, oxygenation, and systolic blood pressure. The PATHOS score showed good calibration and high discrimination, with an area under the receiver operating characteristics curve of 0.83 (95% confidence interval [CI], 0.77-0.89) in the derivation population and 0.74 (95% CI, 0.68-0.80) in the validation cohort, which is significantly higher than the PESI, sPESI, and shock index in both cohorts (P<0.01 for all comparisons). CONCLUSION: PATHOS is a simple and effective prognostic score for predicting IHM in patients with PE in an emergency setting.

Cerebrospinal fluid top-down proteomics evidenced the potential biomarker role of LVV- and VV-hemorphin-7 in posterior cranial fossa pediatric brain tumors.

Posterior cranial fossa is the most frequent location of pediatric brain tumors. Its diagnosis is currently performed by postsurgery histopathology and the identification of biomarkers in cerebrospinal fluid (CSF) could provide a less invasive tool. Patient CSF was collected during surgery before the tumor removal (PRE-CSF) and 6 days after the resection (POST-CSF) and analyzed by top down LC-MS proteomics for comparison. The PRE-CSFs generally exhibited a less complex LC-MS profile than the relative POST-CSFs suggesting a suppressive role of the tumor toward proteins and peptides production or release. Particularly, a panel of peptides, identified as alpha- and beta-hemoglobin chains fragments, were generally absent in the PRE-CSF and present in the POST ones independently from contaminant blood hemoglobin. Among them, the LVV- and VV-hemorphin-7 showed the most repeatable trend and with a few remarkable exceptions: their unusual absence in POST surgery CSF was in fact interestingly correlated to the presence of tumor in the patient despite surgery due to metastases or to subtotal resection. These results ascribed a relevant biological role to LVV- and VV-h7 peptides in the disease and a strong potential as biomarkers. Their analysis in POST surgery CSF could be used to predict patient prognosis.

Sudden paraplegia in a case of apparently isolated frontal embryonal tumour with abundant neuropil and true rosettes.

The exceptional case of a 19-month-old boy with an apparently isolated frontal lesion and a huge holocord neoplastic involvement, presenting with a subtly indolent preoperative course and a particularly tumultuous evolution, is reported. The diagnosis of embryonal tumour with abundant neuropil and true rosettes was posed.

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.

Vascular intracranial malformations and dementia: An under-estimated cause and clinical correlation. Clinical note.

Cerebrovascular malformations (CVMs) such as arteriovenous malformations (AVMs) or dural arteriovenous fistulas (DAVFs) represent a possible source of intracranial hemorrhage, but these malformations can also manifest with neurologic disorders secondary to ischemic penumbra from vascular steal. In the latter case, the clinical manifestations are less obvious and characteristic, and may include a varied clinical spectrum ranging from focal deficits to generalized malfunction of the brain parenchyma resulting in dementia. Dementias secondary to CVMs constitute a probably underestimated subpopulation of patients of great interest because they present with devastating but potentially reversible cognitive impairment. We examined the pertinent literature regarding the clinical manifestations of CVMs characterized by cognitive impairment and describe the distinctive clinical features. Our results confirm that cognitive impairment is one of the clinical manifestations of CVMs and is a frequently misrecognized and often late-diagnosed cause of reversible dementia.

Preoperative 3D volume reconstruction of the posterior wall of the sphenoid sinus with Horos: A free, simple and reliable tool in endoscopic endonasal trans-sphenoidal surgery.

BACKGROUND: The purpose of the study was to create computer-aided design models of the sphenoid sinus with a free-source software in order to perform a preoperative planning during trans-sphenoidal endoscopic surgery (TES) and clarify the three-dimensional anatomical features of the sphenoid sinus and its surrounding structures. METHODS: For each patient a 3D volume rendering of the sphenoid sinus was obtained from a thin slice head and maxilla-facial CT scan using a free-source DICOM viewer. The 3D models obtained preoperatively were examined preoperatively by six neurosurgeons in order to identify the boundaries of the sella. RESULTS: For the main anatomical landmark, all of the observers were able to recognize the anatomical structure at a rate ranging from 80 to 98%, 28 to 60% and 25 to 58% for expert (n=3), inexpert (n=3) and the entire group of observers (n=6), respectively. The analysis of the data shows that both observation groups presented a lower recognition rate of the following parameters: right and left medial and lateral optocarotid recesses and tumor prominence, however, the sellar prominence, clival recess, planum sphenoidalis, right and left ICA prominence, right and left optic prominences represent the main anatomical landmarks to be recognized during TES immediately before the opening of the sellar floor. CONCLUSIONS: The use of a preoperative 3D imaging is not in itself a novelty in the literature, however the fact that a simple tool obtained with a free-source software like Horos can represent a considerable help in surgical practice without resorting to the use of more complex software and expensive represents the real utility of this work.

Giant Prolactinoma Embedded by Pseudoaneurysm of the Cavernous Carotid Artery Treated with a Tailored Therapeutic Scheme.

The coexistence of intracranial aneurysm (IA) is generally thought to be highest in patients with pituitary adenomas (PAs). Different mechanisms may play a role in aneurysm formation, but whether the PA contributes to aneurysm formation is still unclear. In the literature, there are numerous reported cases of this association; however, the analyses of the characteristics of PAs, aneurysms, and treatment management are rare and limited to a restricted number of case reports. We report a rare case of an embedded aneurysm in a macroprolactinoma treated with therapeutic management tailored to the clinical, neurological, and radiological characteristics of the patient. To select the best treatment, we reviewed the literature and reported the only cases in which the radiological characteristics of aneurysms, PAs, therapeutic management, and patient outcome are described. We aimed to understand what are the variables that determine the best therapeutic management with the best possible outcome. The presence of a large pseudoaneurysm of the internal carotid artery completely embedded in a giant macroprolactinoma is rare and needs a tailored treatment strategy. The importance of the preoperative knowledge of asymptomatic IA coexisting with PA can avoid accidental rupture of the aneurysm during surgical resection and may lead to planning the best treatment. A high degree of suspicion for an associated aneurysm is needed, and if magnetic resonance imaging shows some atypical features, digital subtraction angiography must be performed prior to contemplating any intervention to avoid iatrogenic aneurysmal rupture. Our multimodal approach with the first-line therapy of low-dose cabergoline to obtain prolactin normalization with minimum risks of aneurysms rupture and subsequent endovascular treatment with flow diverter has not been described elsewhere to our knowledge. In the cases, we suggest adopting a tailored low-dose cabergoline therapy scheme to avoid rupture during cytoreduction and initiate a close neuroradiological follow-up program.