Epithelial ovarian cancer and brain metastases: might the BRCA status, PARP inhibitor administration, and surgical treatment impact the survival?

OBJECTIVE: To evaluate disease characteristics and survival according to BRCA status, administration of poly-(ADP-ribose) polymerase inhibitors (PARPi), and surgery in patients with ovarian cancer and brain metastases. METHODS: This is a monocentric retrospective cohort of patients with ovarian cancer and brain metastases treated between 2000 and 2021. Data were collected by a retrospective review of medical records and analyzed according to: (1) BRCA mutation; (2) PARPi before and after brain metastases; (3) surgery for brain metastases. RESULTS: Eighty-five patients with ovarian cancer and brain metastasis and known BRCA status (31 BRCA mutated (BRCAm), 54 BRCA wild-type (BRCAwt)) were analyzed. Twenty-two patients had received PARPi before brain metastases diagnosis (11 BRCAm, 11 BRCAwt) and 12 after (8 BRCAm, 4 BRCAwt). Brain metastases occurred >1 year later in patients who had received previous PARPi. Survival was longer in the BRCAm group (median post-brain metastasis survival: BRCAm 23 months vs BRCAwt 8 months, p=0.0015). No differences were found based on BRCA status analyzing the population who did not receive PARPi after brain metastasis (median post-brain metastasis survival: BRCAm 8 months vs BRCAwt 8 months, p=0.31). In the BRCAm group, survival was worse in patients who had received previous PARPi (median post-brain metastasis survival: PARPi before, 7 months vs no-PARPi before, 24 months, p=0.003). If PARPi was administered after brain metastases, survival of the overall population improved (median post-brain metastasis survival: PARPi after, 46 months vs no-PARPi after, 8 months, p=0.00038).In cases of surgery for brain metastases, the prognosis seemed better (median post-brain metastasis survival: surgery 13 months vs no-surgery 8 months, p=0.036). Three variables were significantly associated with prolonged survival at multivariate analysis: BRCA mutation, multimodal treatment, and ≤1 previous chemotherapy line. CONCLUSIONS: BRCA mutations might impact brain metastasis occurrence and lead to better outcomes. In a multimodal treatment, surgery seems to affect survival even in cases of extracranial disease. PARPi use should be considered as it seems to prolong survival if administered after brain metastasis.

Eosinophilic granuloma of the calvarium: is conservative management a valid option? Illustrative case and systematic review of the literature.

INTRODUCTION: Eosinophilic granuloma (EG) is the most common form of Langerhans cell histiocytosis, presenting as a single osteolytic lesion of the calvarium. Its diagnosis is based on typical clinical and radiological features. While surgical resection has been the standard treatment for EG, growing evidence favors watchful waiting, as unifocal calvarial lesions appear to frequently undergo spontaneous remission. However, histopathological confirmations of this hypothesis are still very limited. METHODS: Methods. Here, we report a case of EG with typical clinical and radiological features which, due to intervening circumstances, was resected in a delayed fashion. Moreover, we perform a systematic review of the literature on conservative management of EG. RESULTS: In our case, histological examination showed ongoing bone regeneration with no traces of the disease. Through our literature review, we found 47 cases of calvarial EG managed with watchful waiting. No active intervention was required in 43 cases (91%). Four patients (9%) received surgery or chemotherapy due to the persistence/progression of symptoms or family request. Three reports other than ours documented spontaneous disease remission in surgically resected EG upon histopathological examination. CONCLUSION: Our report provides further evidence that watchful waiting can be a reasonable option in the management of single calvarial EG.

Atlas invagination through the foramen magnum: expanding the spectrum of craniovertebral junction malformations.

PURPOSE: Malformations of the craniovertebral junction (CVJ) range from mild, asymptomatic conditions to severe forms of instability with basilar invagination. Rarely, there have been accounts of forms of so-called paramedian basilar invagination, with abnormal bone masses invading the lateral portion of the foramen magnum. All these entities have been comprehensively classified both from an anatomical and embryological standpoint. METHODS: Here, we report a case of a unique CVJ malformation which is not included in any existing classification framework and could represent a novel pathologic entity. We also provide an overview of the pertinent literature. RESULTS: The patient was a 14-year-old boy with a recent onset of spastic tetraparesis. Radiological studies documented a malformation of the atlas which invaginated through the foramen magnum, causing anterolateral medullary incarceration. Surgical treatment involved posterior decompression with resection of the abnormal bone and occipito-cervical fusion. CONCLUSION: Our report enriches the panorama of CVJ malformations, showing how anatomical knowledge and embryological insights constitute the basis for the correct assessment and treatment of these complex entities.

Bleeding risk evaluation in cerebral cavernous malformation, the role of medications, and hemorrhagic factors: a case-control study.

OBJECTIVE: Cerebral cavernous malformations (CCMs) are vascular lesions with an overall risk of rupture from 2% to 6% per year, which is associated with significant morbidity and mortality. The diagnostic incidence is increasing, so it is of paramount importance to stratify patients based on their risk of rupture. Data in the literature seem to suggest that specific medications, particularly antithrombotic and cardiovascular agents, are associated with a reduced risk of bleeding. However, the effect of the patient coagulative status on the cumulative bleeding risk remains unclear. The aim of this study was to assess the impact of different radiological, clinical, and pharmacological factors on the bleeding risk of CCMs and to assess the predictive power of an already validated scale for general bleeding risk, the HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly). METHOD: This was a multicenter retrospective observational study. The authors collected imaging, clinical status, and therapy data on patients with bleeding and nonbleeding CCMs. Univariate analysis and subsequent multivariate logistic regression were performed between the considered variables and bleeding or nonbleeding status to identify potential independent predictors of bleeding. RESULTS: The authors collected data on 257 patients (46.7% male, 25.3% with bleeding CCMs). Compared with patients with nonbleeding lesions, those with bleeding CCMs were younger, less frequently had hypertension, and less frequently required antiplatelet drugs and beta-blockers (all p < 0.05). Bleeding lesions, however, had significantly higher median volumes (1050 mm3 vs 523 mm3 , p < 0.001). On multivariate analyses, after adjusting for age, history of hypertension and diabetes, and use of antiplatelet drugs or beta-blockers, lesion volume ≥ 300 mm3 was the only significant predictor of bleeding (adjusted OR 3.11, 95% CI 1.09-8.86). When the diagnostic accuracy of different volume thresholds was explored, volume ≥ 300 mm3 showed a limited sensitivity (36.7%, 95% CI 24.6%-50.0%), but a high specificity 78.2% (95% CI 71.3%-84.2%), with an area under the curve of 0.57 (95% CI 0.51-0.64). CONCLUSIONS: This study supports previous findings that the CCM volume is the only factor influencing the bleeding risk. Antithrombotic agents and propranolol seem to have a protective role against the bleeding events. A high HAS-BLED score was not associated with an increased bleeding risk. Further studies are needed to confirm these results.

Repeated surgery for hemorrhagic brain metastases from hepatocellular carcinoma: palliation or effective part of a multimodal treatment? A case-based approach.

Brain metastases from hepatocellular carcinoma (HCCBM) are encountered very rarely in clinical practice, especially in western countries. Only a minority of patients undergoes resective surgery, as clinical picture is usually complex and presentation is often catastrophic with intra-cerebral hemorrhage (ICH). Neurosurgical intervention can be not only life-saving but may also alleviate significantly the burden of symptoms. We present the case of a patient with six metachronous hemorrhagic HCCBM in which emergent surgery extended survival by 9 months, of which seven spent in near-normal life quality, stressing the role of neurosurgery in the evaluation of HCCBM patients.

Treatment of Cystic Craniopharyngiomas: An Update.

In spite of the significant technical and technological progress in neurosurgery and the continuous discoveries by the basic research, adamantinomatous craniopharyngioma remains a significant clinical challenge. Actually, the huge size of the tumor, its multiple cystic components, the encasement of Willis' circle and optic pathways, and the invasion of the hypothalamus often prevent its safe surgical resection. Moreover, the local aggressiveness of the tumor accounts for a high risk of recurrence even after a gross total resection. For these reasons, more and more efforts are being dedicated to enhance the knowledge about AC and improve the tools for its treatment.This paper is dedicated to the most recent advances concerning the AC management. Promising, new insights come for the basic research, thanks to the updates on the role of the WNT-ß-catenin pathway (important for the tumor genesis and progression, not yet developed enough for a safe target therapy in children but useful for determining the prognosis) and the inflammatory mediators (widely overexpressed, especially by the cyst of the tumor, and for which target therapies are being developed). Moreover, further factors and pathways are under investigation.Also the development of new treatment strategies accounts for the improvement of the prognosis and the quality of life of AC patients. The enhancement of the experience with the endoscopic techniques (both transsphenoidal and transventricular approaches) actually allows to perform a less invasive but effective surgery that can be coupled with new modalities of radiation therapy aiming at obtaining a reliable control of the disease and protecting the endocrinological, ophthalmological, and neurological functions. A special mention is finally deserved by the techniques specifically designed for the intracystic therapy (as cyst fenestration alone or in combination with administration of radionuclides or bleomycin or interferon-α) that are here analyzed together with the aforementioned advances.

Functional and morphological changes in hypoplasic posterior fossa.

BACKGROUND: The knowledge of the development and the anatomy of the posterior cranial fossa (PCF) is crucial to define the occurrence and the prognosis of diseases where the surface and/or the volume of PCF is reduced, as several forms of craniosynostosis or Chiari type I malformation (CIM). To understand the functional and morphological changes resulting from such a hypoplasia is mandatory for their correct management. The purpose of this article is to review the pertinent literature to provide an update on this topic. METHODS: The related and most recent literature addressing the issue of the changes in hypoplasic PCF has been reviewed with particular interest in the studies focusing on the PCF characteristics in craniosynostosis, CIM, and achondroplasia. RESULTS AND CONCLUSIONS: In craniosynostoses, namely, the syndromic ones, PCF shows different degrees of hypoplasia, according to the different pattern and timing of early suture fusion. Several factors concur to PCF hypoplasia and contribute to the resulting problems (CIM, hydrocephalus), as the fusion of the major and minor sutures of the lambdoid arch, the involvement of the basal synchondroses, and the occlusion of the jugular foramina. The combination of these factors explains the variety of the clinical and radiological phenotypes. In primary CIM, the matter is complicated by the evidence that, in spite of impaired PCF 2D measurements and theories on the mesodermal defect, the PCF volumetry is often comparable to healthy subjects. CIM is revealed by the overcrowding of the foramen magnum that is the result of a cranio-cerebral disproportion (altered PCF brain volume/PCF total volume). Sometimes, this disproportion is evident and can be demonstrated (basilar invagination, real PCF hypoplasia); sometimes, it is not. Some recent genetic observations would suggest that CIM is the result of an excessive growth of the neural tissue rather than a reduced growth of PCF bones. Finally, in achondroplasia, both macrocephaly and reduced 2D and 3D values of PCF occur. Some aspects of this disease remain partially obscure, as the rare incidence of hydrocephalus and syringomyelia and the common occurrence of asymptomatic upper cervical spinal cord damage. On the other hand, the low rate of CIM could be explained on the basis of the reduced area of the foramen magnum, which would prevent the hindbrain herniation.

Long-term effect of subthalamic and pallidal deep brain stimulation for status dystonicus in children with methylmalonic acidemia and GNAO1 mutation.

Status dystonicus (SD) is a rare and potentially life-threatening condition requiring intensive care management. Deep brain stimulation (DBS) has emerged as an effective treatment for SD refractory to medical management, but its application in this field is still limited. Here, we report the long-term outcome of four pediatric patients treated with DBS at the University Hospital of Padua, Italy, for SD refractory to medications. In addition, we present the results of a systematic literature review aimed at identifying published cases of SD treated with DBS, with focus on motor outcome. In our cohort, two children were affected by methylmalonic acidemia and suffered acute basal ganglia lesions, while the other two carried a pathogenic mutation in GNAO1 gene. DBS target was subthalamic nucleus (STN) in one case and globus pallidus internus (GPi) in three. All patients experienced SD resolution within 8-19 days after surgery. Mean post-operative follow-up was 5 years. We identified in the literature 53 additional SD cases treated with DBS (median age at DBS implantation: 12 years) with reported positive outcome in 51 and resolution of SD in a mean of 17 days after surgery. Our findings indicate that DBS is an effective treatment for SD refractory to medications, even in patients with acute basal ganglia lesions; STN can be an appropriate target when GPi is damaged. Moreover, data from long-term follow-up show that SD recurrences can be significantly reduced in frequency or abolished after DBS implantation.

Chiari Formation or Malformation? Trends in the Pathophysiology and Surgical Treatment of an Ever-Elusive Entity.

Background: Chiari malformation type 1 (CM1) remains a complex neurosurgical condition with ongoing debate regarding its optimal management. Methods: This narrative review examines key controversies surrounding the pathophysiology, surgical indications, and treatment strategies for CM1. Results: We highlight the challenges posed by the wide spectrum of CM variants and the evolving understanding of its association with syringomyelia, basilar invagination, and craniovertebral instability. Emerging surgical techniques, including minimally invasive approaches and the use of new technologies such as endoscopes and exoscopes, are evaluated for their potential to improve outcomes. Recent consensus guidelines are also discussed. Conclusions: The need for individualized treatment plans for CM1 is emphasized, with special focus put on the connection between novel pathophysiological insights, technological advancements and opportunities for a more nuanced surgical management. Further research is necessary to establish solid foundations for more individualized treatments.

A Three-Step Submandibular Retropharyngeal Approach to the Craniovertebral Junction: Is Less Always More?

Background: Accessing the craniovertebral junction poses unique challenges due to its anatomical complexity and proximity to critical structures, such as the cord-brainstem junction, great vessels of the neck, cranial nerves, oropharynx, and rhinopharynx. Among the approaches that have been developed over the years, the submandibular retropharyngeal approach offers good antero-lateral access without the need of transgressing mucosal layers. In its traditional form, however, this approach involves multiple sequential steps and requires intricate dissection, extensive retraction, and meticulous maneuvering, which can increase operative time and produce approach-related morbidity. Methods: With this paper, we propose a simplified technique for a submandibular retropharyngeal approach involving only three surgical steps. The advantages and limitations of this technique are illustrated through three surgical cases of neoplastic and degenerative craniovertebral junction pathologies. Results: In two out of the three cases, our technique allowed for a wide exposure of the lesions that could be resected totally or sub-totally with good outcome. In one case with involvement of the clivus and the occipital condyle, the exposure was inadequate; a biopsy was obtained, and the lesion was subsequently resected via and endoscopic transmucosal approach. Conclusions: Our technique represents a significant simplification of the traditional submandibular retropharyngeal approach; with appropriate indication, it permits a fast, safe, and adequate exposure of craniovertebral junction pathologies.

Spinal lymphangiomas: Case-based review of a chameleonic disease entity.

Purpose: Lymphangiomas are benign hamartomas in the spectrum of lymphatic malformations, exhibiting multifaceted clinical features. Spinal involvement is exceedingly rare, with only 35 cases reported to date. Both due to their rarity and chameleonic radiologic features, spinal lymphangiomas (SLs) are usually misdiagnosed; postoperatively, surgeons are thus confronted with an unexpected histopathological diagnosis with sparse pertinent literature and no treatment guidelines available. Methods: Here, we report the case of a 67-year-old female who underwent surgery for a T6-T7 epidural SL with transforaminal extension, manifesting with spastic paraparesis. Then, we present the results of the first systematic review of the literature on this subject, delineating the clinical and imaging features and the therapeutic implications of this rare disease entity. Results: Our patient was treated with T6-T7 hemilaminectomy and resection of the epidural mass, with complete recovery of her neurological picture. No recurrence was evident at 18 months. In the literature, 35 cases of SL were reported that can be classified as vertebral SL (n = 18), epidural SL (n = 10), intradural SL (n = 3), or intrathoracic lymphangiomas with secondary spinal involvement (n = 4). Specific treatment strategies (both surgical and nonsurgical) were adopted in relation to each of these categories. Conclusion: Gathering knowledge about SL is fundamental to promote both correct preoperative identification and appropriate perioperative management of this rare disease entity. By reviewing the literature and discussing an exemplary case, we delineate a framework that can guide surgeons facing such an unfamiliar diagnosis.

3D Printing for Customized Bone Reconstruction in Spheno-Orbital Meningiomas: A Systematic Literature Review and Institutional Experience.

Background: The treatment of spheno-orbital meningiomas (SOMs) requires extensive bone resections, creating significant defects in a complex geometrical space. Bone reconstruction represents a fundamental step that optimizes long-term aesthetic and functional outcomes. In recent years, 3D printing technology has also been exploited for complex skull base reconstructions, but reports remain scarce. Methods: We retrospectively analyzed four consecutive patients who underwent SOM resection and one-step 3D PEEK customized reconstruction from 2019 to 2023. A systematic review of 3D printing customized implants for SOM was then performed. Results: All patients underwent a frontotemporal craniotomy, removal of SOM, and reconstruction of the superolateral orbital wall and pterional region. The aesthetic outcome was extremely satisfactory in all cases. No orbital implant malposition or infectious complications were documented. Eleven papers were included in the literature review, describing 27 patients. Most (23) patients underwent a single-stage reconstruction; in three cases, the implant was positioned to correct postoperative delayed enophthalmos. Porous titanium was the most used material (16 patients), while PEEK was used in three cases. Prosthesis malposition was described in two (7.4%) patients. Conclusions: Single-step reconstruction with a personalized 3D PEEK prosthesis represents a valid reconstruction technique for the treatment of SOMs with good aesthetic outcomes.

Geometry and Symmetry of Willis' Circle and Middle Cerebral Artery Aneurysms Development.

Background: A relationship between the geometry and symmetry of Willis' circle and intracranial aneurysms was reported for anterior communicating and posterior communicating (PCom) aneurysms. A similar association with the middle cerebral artery (MCA) aneurysms instead appeared weaker. Methods: We reviewed 432 patients from six Italian centers with unilateral MCA aneurysms, analyzing the relationship between the caliber and symmetry of Willis' circle and the presence of ruptured and unruptured presentation. CT-angiograms were evaluated to assess Willis' circle geometrical characteristics and the MCA aneurysm side, dimension and rupture status. Results: The hypoplasia of the first segment of the anterior cerebral artery (A1) was in approximately one-quarter of patients and PCom hypoplasia was in almost 40%. About 9% had a fetal PCom ipsilaterally to the aneurysm. By comparing the aneurysmal and healthy sides, only the PCom hypoplasia appeared significantly higher in the affected side. Finally, the caliber of the internal carotid artery (ICA) and the first segment of MCA (M1) caliber were significantly greater in patients with unruptured aneurysms, and PCom hypoplasia appeared related to the incidence of an ipsilateral MCA aneurysm and its risk of rupture. Conclusions: Although according to these findings asymmetries of Willis' circle are shown to be a risk factor for MCA aneurysm formation and rupture, the indifferent association with ipsilateral or contralateral hypoplasia remains a datum of difficult hemodynamic interpretation, thereby raising the concern that this association may be more casual than causal.

Integrated Neurosurgical Management of Retroperitoneal Benign Nerve Sheath Tumors.

Peripheral nerve sheath tumors (PNST) of the retroperitoneum are rare and are often treated by general surgeons dealing with retroperitoneal cancers. However, resection without the correct microsurgical technique can cause permanent neurological deficits and pain. Here, we discuss our interdisciplinary approach based on the integration of expertise from neurosurgery and abdominal surgery, allowing for both safe exposure and nerve-sparing microsurgical resection of these lesions. We present a series of 15 patients who underwent resection of benign retroperitoneal or pelvic PNST at our institution. The mean age of patients was 48.4 years; 67% were female. Tumors were 14 schwannomas and 1 neurofibroma. Eight patients (53%) reported neurologic symptoms preoperatively. The rate of complete resection was 87% (n = 13); all symptomatic patients showed improvement of their preoperative symptoms. There were no postoperative motor deficits; one patient (7%) developed a permanent sensory deficit. At a mean postoperative follow-up of 31 months, we observed no recurrences. To our best knowledge, this is the second-largest series of benign retroperitoneal PNST consistently managed with microsurgical techniques. Our experience confirms that interdisciplinary management allows for safe treatment of these tumors with good neurological and oncological outcomes.

Decompression with or without Fusion for Lumbar Synovial Cysts-A Systematic Review and Meta-Analysis.

The management of symptomatic lumbar synovial cysts (LSC) is still a matter of debate. Previous systematic reviews did not stratify data according to different treatment techniques or incompletely reported comparative data on patients treated with lumbar posterior decompression (LPD) and lumbar decompression and fusion (LDF). The aim of our study was to compare LPD and LDF via a systematic review and meta-analysis of the existing literature. The design of this study was in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review questions were as follows: among patients suffering from symptomatic lumbar synovial cysts (population) and treated with either posterior lumbar decompression or posterior decompression with fusion (intervention), who gets the best results (outcome), in terms of cyst recurrence, reoperation rates, and improvement of postoperative symptoms (comparison)? The search of the literature yielded a total of 1218 results. Duplicate records were then removed (n = 589). A total of 598 articles were screened, and 587 records were excluded via title and abstract screening; 11 studies were found to be relevant to our research question and were assessed for eligibility. Upon full-text review, 5 were excluded because they failed to report any parameter separately for both LPD and LDF. Finally, 6 studies for a total of 657 patients meeting the criteria stated above were included in the present investigation. Our analysis showed that LDF is associated with better results in terms of lower postoperative back pain and cyst recurrence compared with LPD. No differences were found in reoperation rates and complication rates between the two techniques. The impact of minimally invasive decompression techniques on the different outcomes in LSC should be assessed in the future and compared with instrumentation techniques.

Comparison Between Intrasylvian and Intracerebral Hematoma Associated with Ruptured Middle Cerebral Artery Aneurysms: Clinical Implications, Technical Considerations, and Outcome Evaluation.

BACKGROUND: Subarachnoid hemorrhage (SAH) due to a middle cerebral artery (MCA) aneurysm rupture is often associated with an intracerebral hematoma (ICH) or intrasylvian hematoma (ISH). METHODS: We reviewed 163 patients with ruptured MCA aneurysms associated with pure SAH or SAH plus ICH or ISH. The patients were first dichotomized according to the presence of a hematoma (ICH or ISH). Next, we performed a subgroup analysis comparing ICH versus ISH to explore their relationship with the most relevant demographic, clinical, and angioarchitectural features. RESULTS: Overall, 85 patients (52%) had a pure SAH, and 78 (48%) had presented with an associated ICH or ISH. No significant differences were observed in the demographics or angioarchitectural features between the 2 groups. However, the Fisher grade and Hunt-Hess score were higher for the patients with hematomas. A good outcome was observed in a higher percentage of patients with pure SAH compared with those with an associated hematoma (76% vs. 44%), although the mortality rates were comparable. Age, Hunt-Hess score, and treatment-related complications were the main outcome predictors on multivariate analysis. Patients with ICH appeared worse clinically compared with those with ISH. We also found that older age, a higher Hunt-Hess score, larger aneurysms, decompressive craniectomy, and treatment-related complications were associated with poor outcomes among the patients with an ISH, but not an ICH, which appeared, per se, as a more severe clinical condition. CONCLUSIONS: Our study has confirmed that age, Hunt-Hess score, and treatment-related complications influence the outcome of patients with ruptured MCA aneurysms. However, in the subgroup analysis of patients with SAH associated with an ICH or ISH, only the Hunt-Hess score at onset appeared as an independent predictor of the outcome.