Anna Michel

Cerebral Cavernous Malformations (CCMs) are low-flow vascular lesions located within the central nervous system, with a reported prevalence in the general population of 0.16–0.5%. Patients with CCMs may remain asymptomatic or present new onset symptoms such as seizures or focal neurological deficits often related to the occurrence of intracerebral hemorrhage. CCM may appear sporadic or as part of familial forms linked to mutations in the CCM-gene cluster, affecting endothelial cell integrity and triggering molecular cascades, including the MEKK3/KLF2/4 signaling pathway. Recent studies have highlighted the roles of inflammatory, angiogenic, and coagulation pathways alongside the emerging evidence of a gut–brain axis influencing microbiome-driven TLR4 signaling. This systematic review aims to describe molecular biomarkers associated with CCM pathophysiology, emphasizing their potential use as diagnostic and prognostic tools. Circulating plasma biomarkers such as CRP, vitamin D, and interleukins may reflect ongoing inflammatory and endothelial processes, while some imaging biomarkers like Quantitative Susceptibility Mapping (QSM) have shown a correlation with iron deposition and vascular leakage. Leveraging both circulating and imaging biomarkers may improve the therapeutic decision-making process. Further studies are encouraged to validate these findings and to facilitate the development of personalized, evidence-based strategies for the management of CCM.

Background/Objectives: Cerebral infarction significantly worsens outcomes after aneurysmal subarachnoid hemorrhage (SAH). This retrospective study analyzed early predictors of infarct-free survival and the impact of infarct timing on clinical outcomes. Methods: We reviewed 988 consecutive SAH patients treated from 2003 to 2016, all with follow-up CT scans. Baseline clinical and SAH characteristics were recorded to identify predictors of infarct-free survival and assess the relationship between infarct timing and outcomes. Results: Cerebral infarctions occurred in 475 patients (48.1%) at a median of 3.4 days post-SAH; 70.9% happened within the first week. Earlier infarctions were associated with higher in-hospital mortality (odds ratio [OR] = 0.91 per day increase, p < 0.0001) and poor 6-month outcomes (modified Rankin Scale > 3; OR = 0.96 per day increase, p = 0.012), especially within 48 h. Independent predictors of infarct-free survival included poor initial condition (WFNS ≥ 4, adjusted hazard ratio [aHR] = 1.82, p < 0.0001), intraventricular hemorrhage (aHR = 1.25, p = 0.041), aneurysm rebleeding (aHR = 1.76, p < 0.0001), acute hydrocephalus (aHR = 1.38, p = 0.020), and daily aspirin intake (aHR = 0.68, p = 0.002). The number of baseline risk factors (0–5) strongly influenced both infarction likelihood and timing (p < 0.0001). Conclusions: Cerebral infarctions predominantly occur within the first week after SAH, with earlier infarctions having a more severe impact on outcomes. Initial risk factor-adapted SAH management may improve functional outcomes.

Objective: Central neurocytomas (CNs), classified as CNS (central nervous system) grade 2 tumors, are exceptionally rare tumors, accounting for approximately 0.1–0.5% of all intracranial neoplasms, and are typically characterized by a benign clinical course and frequent association with hydrocephalus. This study aims to present a comprehensive analysis of surgical and adjuvant therapies for CN. Methods: The study comprised all patients who underwent microsurgical tumor removal in our center over the past decade (2013–2023). Clinical manifestations, surgical and adjuvant therapy approaches, MRI and histological findings, clinical outcomes, and recurrence-free survival were evaluated. Results: A total of eleven patients (six men, mean age of 28.0 years; five women, mean age of 53.6 years) underwent surgical treatment. Intraventricular tumors were the most common (72.7%, n = 8). The predominant presenting symptoms were headache and visual disturbances. All tumors exhibited contrast enhancement on MRI. Hydrocephalus was present in five patients. The Ki67 proliferation index ranged from 2% to 10%, with nine patients exhibiting Ki67 > 3%. The median recurrence-free survival was 38.0 months (IQR: 25.0–53.0). The most severe postoperative complications included aphasia, hemiparesis, and memory impairment, resulting in a postoperative Karnofsky Performance Status (KPS) below 70% in five patients. Follow-up assessments showed significant symptomatic improvement in all affected patients. Conclusions: Gross total resection is the recommended first-line therapy with favorable neurological outcomes and for atypical CN as well. Adjuvant radiotherapy should be reserved for tumor progression and recurrence. The role of adjuvant chemotherapy remains unclear, but it may be an option for CN with a high proliferation index.

Purpose: Breast cancer (BC) is one of the most common primary tumor entities that develop brain metastases (BM) during disease progression. Multiple BM are associated with poorer prognosis, but various surgical, radiotherapeutic and systemic treatment approaches improve survival. We aimed to identify prognostic factors and evaluate the overall survival following BM surgery in patients with multiple BCBM. Methods: All metachronous metastasized female patients with resected BCBM at our institution between 2008 and 2019 were included. Data on clinical, radiologic, and histopathologic parameters were recorded and analyzed using univariate and multivariate regression models. Results: Among the 93 patients included in the final analysis, 30 individuals presented with multiple BM. Compared to patients with single BM, those with multiple BM were more likely to have infratentorial BM (adjusted odds ratio [aOR] 3.35, 95% confidence interval [CI] 1.03–10.83, p = 0.044), HER2(human epidermal growth factor receptor 2)-positive BC (aOR 3.93, 95% CI 1.23–12.53, p = 0.021) and hepatic metastases (aOR 5.86, 95% CI 1.34–25.61, p = 0.019). There was no significant difference in postoperative survival between individuals with multiple (median: 12.5 months) and single BM (17.0 months, p = 0.186). In the multivariate Cox regression analysis, adjuvant radiotherapy (adjusted hazard ratio [aHR] 5.93, 95% CI 1.06–33.26, p = 0.043) and trastuzumab treatment (aHR 4.95, 95% CI 1.72–14.25, p = 0.003) were associated with longer postoperative survival multiple BCBM patients. Conclusion: BC patients with multiple BM show remarkable postoperative survival, particularly if combined with adjuvant radiotherapy. Our data justify the surgery of multiple BCBM in patients with appropriate clinical condition and feasible location of BM.

Background: Rosette-forming glioneuronal tumor (RGNT) is an extremely rare entity described for the first time in the WHO classification of tumors of the central nervous system in 2007. Predominantly, single case reports of RGNT in the pineal region have been published, and specific therapy concepts are pending. Methods: The study group comprised all patients with the RGNT (CNS WHO grade 1) in the pineal region that underwent microsurgical tumor removal in our center (August 2018–June 2021). Surgical strategy, histological findings, and clinical outcome are presented, and the results are evaluated and compared to published case reports. Results: Four male patients aged under 50 years (range between 20 and 48 years) and one female patient, 51 years old, were included in this study. Chronic headaches and generalized epileptic seizures were the main symptoms. Supra-cerebellar infratentorial gross total tumor resection (GTR) was performed in two cases, two patients underwent subtotal tumor resection, and an endoscopic biopsy was performed in case five. Conclusion: In cases where surgical resection seems feasible with a reasonable surgical risk, we advocate GTR. Regular and long-term MRI follow-up is essential to detect a slow tumor progression. The role of additional chemotherapy or radiotherapy remains unclear.

Purpose: Breast cancer (BC) is the most frequently diagnosed tumor entity in women. Occurring at different time intervals (TI) after BC diagnosis, brain metastases (BM) are associated with poor prognosis. We aimed to identify the risk factors related to and the clinical impact of timing on overall survival (OS) after BM surgery. Methods: We included 93 female patients who underwent BC BM surgery in our institution (2008–2019). Various clinical, radiographic, and histopathologic markers were analyzed with respect to TI and OS. Results: The median TI was 45.0 months (range: 9–334.0 months). Fifteen individuals (16.1%) showed late occurrence of BM (TI ≥ 10 years), which was independently related to invasive lobular BC [adjusted odds ratio (aOR) 9.49, 95% confidence interval (CI) 1.47–61.39, p = 0.018] and adjuvant breast radiation (aOR 0.12, 95% CI 0.02–0.67, p = 0.016). Shorter TI (< 5 years, aOR 4.28, 95% CI 1.46–12.53, p = 0.008) was independently associated with postoperative survival and independently associated with the Union for International Cancer Control stage (UICC) III–IV of BC (aOR 4.82, 95% CI 1.10–21.17, p = 0.037), midline brain shift in preoperative imaging (aOR10.35, 95% CI 1.09–98.33, p = 0.042) and identic estrogen receptor status in BM (aOR 4.56, 95% CI 1.35–15.40, p = 0.015). Conclusions: Several factors seem to influence the period between BC and BM. Occurrence of BM within five years is independently associated with poorer prognosis after BM surgery. Patients with invasive lobular BC and without adjuvant breast radiation are more likely to develop BM after a long progression-free survival necessitating more prolonged cancer aftercare of these individuals.

Background: Brain metastases requiring surgical treatment determine the prognosis of patients with breast cancer. We aimed to develop the scores for the prediction of short (n = 95), 18 (18.9%) and 22 (23.2%) patients experienced short and long postoperative survival, respectively. Breast-preserving surgery, presence of multiple brain metastases and age ≥ 65 years at breast cancer diagnosis were identified as independent predictors of short postoperative survival. In turn, positive HER2 receptor status in brain metastases, time interval ≥ 3 years between breast cancer and brain metastases diagnosis and KPS ≥ 90% independently predicted long survival. The appropriate short and long survival scores showed higher diagnostic accuracy for the prediction of short (AUC = 0.773) and long (AUC = 0.775) survival than the breast Graded Prognostic Assessment score (AUC = 0.498/0.615). A cumulative survival score (total score) showed significant association with overall survival (p = 0.001). Conclusion: We identified predictors independently impacting the prognosis after BCBM surgery. After external validation, the presented scores might become useful tools for the selection of proper candidates for BCBM surgery.