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Background The benefit and the risk profile of Gamma Knife radiosurgery (GKRS) for intracerebral cavernoma remains incompletely defined in part due to the natural history of low incidence of bleeding and spontaneous regression of this vascular malformation. In this study, we retrieved cases from a prospectively collected database to assess the outcome of intracerebral cavernoma treated with GKRS using a double blinded review process for treatment. Methods From 2003 to 2018, there were 94 cases of cavernoma treated by GKRS in the doubly blinded assessments by two experienced neurological and approved for GKRS treatment. All the patients received GKRS with margin dose of 11–12 (Gray) Gy and afterwards were assessed for neurological outcome, radiologic response, and quality of life. Results The median age of the patients was 48 (15–85) years with median follow up of 77 (26–180) months post SRS. The mean target volume was 1.93 ± 3.45 cc. In those who has pre-SRS epilepsy, 7 of 16 (43.7%) achieved seizure freedom (Engel I/II) and 9 of 16 (56.3%) achieved decreased seizures (Engel III) after SRS. Rebleeding occurred in 2 cases (2.1%) at 13 and 52 months post SRS. The radiologic assessment demonstrated 20 (21.3%) cases of decreased cavernoma volume, 69 (73.4%) were stable, and 5 (7.3%) increased size. Eighty-seven of 94 (92.5%) cases at the last follow up achieve improvement in their quality of life, but 7 cases (7.4%) showed a deterioration. In statistical analysis, the effective seizure control class (Engel I/II) was highly correlated with patient harboring a single lesion ( p  < 0.05) and deep seated location of the cavernoma ( p  < 0.01). New neurological deficits were highly correlated with decreased mental ( p  < 0.001) and physical ( p  < 0.05) components of quality of life testing, KPS ( p  < 0.001), deep seated location ( p  < 0.01), and increased nidus volume ( p  < 0.05). Quality of life deterioration either in physical component ( p  < 0.01), mental component ( p  < 0.01), and KPS ( p  < 0.05) was highly correlated with increased cavernoma volume. Conclusion Low margin dose GKRS for intracerebral cavernoma offers reasonable seizure control and improved quality of life while conferring a low risk of treatment complications including adverse radiation effect.

This study aims to demonstrate the effect of gamma knife radiosurgery (GKRS) on symptoms, hemorrhage rates, and histopathological changes in patients with cavernous malformations (CMs), regardless of whether the symptomatic lesions are hemorrhagic. This single-center retrospective study evaluated symptomatic patients with single CMs treated with GKRS between 2016 and 2023. The patients’ demographic data, presenting symptoms, GKRS radiation dose, complications developed during follow-up (hemorrhage, radiotoxicity), the rate of symptom improvement, and histopathological changes of surgically removed CMs were recorded. Our study included 134 symptomatic patients, of whom 55 were male (41%) and 79 were female (59%). Among the patients, 80 (59.7%) had CMs in the lobar region, 23 (17.1%) in the cerebellum, 16 (12%) in the brainstem, and 15 (11.2%) in the basal nuclei/thalamus. The mean target volume was 0.64 ± 1.23 cm 3 , and the mean tumor margin dose was 14.89 ± 1.90 Gy. Symptoms were completely recovered in 95 patients (70.9%), while 18 (13.4%) experienced partial recovery. The annual hemorrhage rate (AHR) reduced from 6.26 to 1.01 following GKRS. Adverse radiation effects (ARE) were encountered in ten patients (7.46%) of cases, with only three patients (2.2%) being permanent. The mean follow-up period was 35.57 ± 23.54 months (2–83 months). Two patients without hemorrhage underwent surgical removal of CM due to symptomatic deterioration after GKRS. Histopathological examination demonstrated numerous vascular structures with luminal narrowing due to hyalinization and fibrinoid necrosis caused after GKRS. Our findings suggest that GKRS may help reduce hemorrhage rates and potentially relieve symptoms in patients with symptomatic CMs, although further long-term studies are necessary to confirm these observations and to fully assess potential risks. Since there is no radiological method to evaluate the impact of GKRS on CMs, our study examines the histopathological changes that occurred following the GKRS. The histopathological changes prove that GKRS alters the morphology of the CMs and thus can relieve symptoms and reduce hemorrhage rates associated with CMs.

Cavernous malformations (CM) of the brain are vascular abnormalities that carry a risk of bleeding, posing significant neurological and life-threatening challenges, particularly in posterior fossa. The efficacy of radiosurgery for cavernomas still remains a matter of debate, largely due to technical and statistical limitations. In this study, we present a series of posterior fossa cavernomas treated using CyberKnife radiosurgery, employing an innovative approach that integrates both technical and statistical advancements. Patients and methods We conducted a prospective series involving 35 posterior fossa cavernomas in 33 patients treated with low-dose radiosurgery protocols (12 Gy in a single fraction or 18 Gy in 3 fractions). Compared to previously published series, our approach targeted a larger treatment volume, encompassing the entire hemosiderin ring surrounding the cavernoma. Radiosurgery was indicated for cases of hemorrhage or progressive neurological deficits in anatomically challenging, nonsurgical areas. The statistical analysis was designed to address the unknown onset time of cavernoma prior to radiosurgery, enabling a more accurate calculation of the hemorrhage incidence rate before treatment. Follow-up evaluations, including clinical assessments and MRI, were conducted at 3-6-9-12-18-24 months and subsequently on an annual basis. Results With a mean follow-up duration of 26 months, exceeding the previously described latency period, and a median [IQR] follow-up of 13 months [8.7-30.4] which represents approximately half the latency period, only one patient experienced a recurrence of hemorrhage, occurring 20 months post-treatment and remaining asymptomatic. No patients exhibited radio-induced parenchymal changes or clinical deterioration following radiosurgery. Conclusions These preliminary results support the strategy of increasing the target volume while reducing the radiation dose for cavernous malformations. We further recommend incorporating sensitivity analyses to evaluate the robustness of results, particularly in the context of uncertainties surrounding the time of onset of cavernomas.

In this study, the dose schedule efficacy, safety and late adverse effects of stereotactic radiosurgery (SRS) were evaluated for patients with symptomatic cavernomas who were not eligible for surgery and treated with SRS. Between January 2013 and December 2018, 53 patients with cavernomas were treated using SRS with the CyberKnife® system. Patients’ diseases were deeply located or were in subcortical functional brain regions. In addition to bleeding, 23 (43.4%) patients had epilepsy, 12 (22.6%) had neurologic symptoms and 16 patients (30.2%) had severe headaches. The median volume was 741 (range, 421–1351) mm3, and the median dose was 15 (range, 14–16) Gy in one fraction. After treatment, six (50%) of 12 patients with neurologic deficits still had deficits. Rebleeding after treatment developed in only two (3.8%) patients. The drug was completely stopped in 14 (60.9%) out of 23 patients who received epilepsy treatment, and the dose of levetiracetam decreased from 2000 mg to 1000 mg in four (17.3%) of nine patients. Radiologically, complete response (CR) was observed in 13 (24.5%) patients, and partial responses (PR) were observed in 32 (60.2%) patients. Clinical response of CR was observed in 30 (56.6%) patients, PR was observed in 16 (30.2%), stable disease (SD) was observed in three (5.7%) and four (7.5%) patients progressed. In conclusion, SRS applied in the appropriate dose schedule may be an effective and reliable method in terms of symptom control and prevention of rebleeding, especially in patients with inoperable cavernomas.

This is a retrospective study examining the efficacy and safety of Gamma Knife radiosurgery (GKS) in treating patients with cerebral cavernous malformations (CCMs). Between 1993 and 2018, 261 patients with 331 symptomatic CCMs were treated by GKS. The median age was 39.9 years and females were predominant (54%). The median volume of CCMs was 3.1 mL. The median margin dose was 11.9 Gy treat to a median isodose level of 59%. Median clinical and imaging follow-up times were 69 and 61 months, respectively. After the initial hemorrhage that led to CCM diagnosis, 136 hemorrhages occurred in the period prior to GKS (annual incidence = 23.6%). After GKS, 15 symptomatic hemorrhages occurred within the first 2 years of follow-up (annual incidence = 3.22%), and 37 symptomatic hemorrhages occurred after the first 2 years of follow-up (annual incidence = 3.16%). Symptomatic radiation-induced complication was encountered in 8 patients (3.1%). Mortality related to GKS occurred in 1 patient (0.4%). In conclusion, GKS decreased the risk of hemorrhage in CCM patients presenting with symptomatic hemorrhage. GKS is a viable alternative treatment option for patients with surgically-inaccessible CCMs or significant medical comorbidities.

ObjectiveTo evaluate the safety and efficacy of SRS treatment of central neurocytomas (CNCs), cavernous sinus hemangiomas (CSHs), and glomus tumors (GTs); and to compare upfront stereotactic radiosurgery (SRS) and adjuvant SRS in the treatment of these hypervascular tumors.MethodsThis was a retrospective review of consecutive CNCs, CSHs, and GTs treated with SRS between 1993 and 2017. Tumor response was categorized based on volumetric analysis on magnetic resonance imaging: (1) tumor regression [> 10% decrease in tumor volume (TV)]; (2) stable tumor (≤ 10% change in TV); or (3) tumor progression (> 10% increase in TV).ResultsSixty hypervascular tumors (CNC: 28; CSH: 16; GT: 16) underwent SRS between 1993 and 2017. Margin doses were 13 Gy, 12 Gy, and 14 Gy for CNCs, CSHs, and GTs, respectively. Tumor regression was observed in 54 tumors (90%) with initial SRS after a median follow-up of 82 months. Relative reductions in TVs for CNCs were 38%, 52%, and 73% at 12, 24, and 48 months, respectively. Relative reductions in TVs for CSHs were 51%, 68%, and 88% at 12, 24, and 48 months, respectively. Relative reductions in TVs for GTs were 22%, 31%, and 47% at 12, 24, and 48 months, respectively. Upfront SRS was performed in 26 patients (43%). No difference in relative TV reductions were found between upfront and adjuvant SRS. Adverse radiation effects were observed in five patients. No mortality was encountered.ConclusionSRS for hypervascular tumors is associated with high rates of tumor regression with low risk of complications. No significant difference in rates of relative TV reduction were found between upfront and adjuvant SRS. Hence, upfront SRS may be considered in select patients.

Cavernous malformations (CMs) are angiographically occult, low-flow vascular malformations of the central nervous system. They are acquired lesions, with approximately 80% of patients having the sporadic form and 20% the familial form of the disease. The lesions may also develop years after radiotherapy. At the microscopic level, they consist of endothelium-lined cavities (or “caverns”) containing blood of different ages. The endothelium proliferates abnormally, and tight junctions are absent or dysfunctional, resulting in leakiness of the endothelium and clinical manifestations in some patients. Cavernous malformations can be an incidental finding or can present with focal neurologic deficits, seizures, or headache, with or without associated hemorrhage. Management of the CM lesion requires knowledge of the natural history of the disease compared with the risk of surgical intervention. Surgery is often considered for symptomatic patients with lesions in a noneloquent location. Medical management is warranted for symptoms related to the CM. Research aimed at understanding the genes and signaling pathways related to CMs have provided potential drug targets, and clinical trials are underway to determine whether medications reduce the risk of future bleeding without surgery or modify the disease course. In addition, recent epidemiologic data have aided practitioners in determining how to treat comorbid conditions in patients with a potentially hemorrhagic lesion. This review provides an overview of the epidemiology, presentation, and clinical management of CMs.

Purpose This retrospective systematic literature review aimed to summarize available data regarding epidemiology, etiology, presentation, investigations, differentials, treatment, prevention, monitoring, complications, and prognosis for radiation-induced cavernous malformations (RICMs) in pediatric patients. Methodology Review conducted per PRISMA guidelines. Google Scholar, PubMed, Trip Medical Database, and Cochrane Library searched utilizing a keyphrase, articles filtered per inclusion/exclusion criteria, duplicates excluded. Based on criteria, 25 articles identified, 7 further excluded from the systematic data but included in discussion (5 × insufficient data, 2 × other systematic reviews). Results Many studies did not contain all explored data. 2487 patients reviewed, 325 later found to have RICM (143 male, 92 female). Mean age at irradiation 7.6 years (range 1.5–19). Mean total radiation dose 56 Gy (12–112). Most common indications for radiation—medulloblastoma 133x, astrocytoma 23x, ependymoma 21x, germinoma 19x. Mean age at RICM diagnosis 18 years (3.6–57). Mean latency to RICM 9.9 years (0.25–41). Most common anatomic locations—temporal 36, frontal 36, parietal 13, basal ganglia 16, infratentorial 20. Clinical presentation—incidental 270, seizures 19, headache 11, focal neurological deficit 7, other 13. 264 patients observed, 34 undergone surgery. RICM bled in 28 patients. Mean follow-up 11.7 years (0.5–50.3). Prognostic reporting highly variable. Conclusions From our data, pediatric RICMs appear to display slight male predominance, present about 10 years after initial irradiation in late teen years, and present incidentally in majority of cases. They are mostly operated on when they bleed, with incidental lesions mostly being observed over time. Further prospective detailed studies needed to draw stronger conclusions.

Cavernous malformation (CM) is the second most common cerebral vascular malformation and is often found incidentally. Their natural history is usually benign, however, patients with CM who present with symptomatic hemorrhage may later follow a serious clinical course if left untreated. The risk of hemorrhage is associated with previous hemorrhage, lesion location (infratentorial and deep), and the presence of associated developmental venous anomaly (DVA). Histopathological specimens also indicate that coexistence of DVA and other vascular malformations may be associated with hemorrhage owing to CMs. Diagnosing CMs is difficult, even in patients who initially present with symptomatic hemorrhage. Computed tomography scans typically reveal a hemorrhagic CM as a nonspecific heterogenous mass of high density, which may not be misdiagnosed as a solitary hematoma, especially when located in the infratentorial region. Magnetic resonance imaging demonstrates internal loculation with mixed-signal intensities typical for CMs, although this may be partially or completely masked by acute hemorrhage. Susceptibility-weighted imaging (SWI) reveals a significant “blooming” effect of hemosiderin deposition. Three-dimensional postcontrast T1-weighted imaging is essential to identify associated DVAs, and this is important for both diagnosis and planning of surgical treatment. Contrast-enhanced MRI should be performed to diagnose hemorrhagic CMs and differentiate them from spontaneous solitary hematoma or hemorrhagic tumors.

Radiation-induced cavernomas (RIC) after cranial radiotherapy have an unknown risk of hemorrhage. Zabramski magnetic resonance imaging (MRI) classification is touted as being able to indicate non-radiation-induced cavernomas hemorrhage risk. The aim of our study was to assess the hemorrhage risk of RIC during long-term follow-up of childhood cancer survivors based on brain MRI examinations. We analyzed retrospectively long-term follow-up data of 36 childhood cancer survivors after initial diagnosis with acute leukemia (n = 18) or brain tumor (n = 18), all treated with cranial radiotherapy. Detected RIC in long-term follow-up brain MRI (1.5 or 3 Tesla) were classified following the Zabramski MRI classification and were categorized into \"high\" (Zabramski type I, II or V) or \"low\" (type III or IV) risk of hemorrhage. 18 patients (50%) showed RIC with a significant relation to the original tumor entity (p = 0.023) and the cumulative radiation dose to the brain (p = 0.016): all 9 childhood cancer survivors diagnosed with medulloblastoma developed RIC. We classified RIC in only 3/36 childhood cancer survivors (8%) (1 patient with acute lymphoblastic leukemia [Zabramski type II] and 2 patients with medulloblastoma [type I and type II]) as high risk for hemorrhage, the remaining RIC were classified as Zabramski type IV with low risk for hemorrhage. None of the childhood cancer survivors with RIC showed symptomatic hemorrhages. RIC are common late effects in childhood cancer survivors treated with cranial radiotherapy affecting half of these patients. However, only a few RIC (occurring in 8% of all reviewed childhood cancer survivors) were classified as high risk for hemorrhage and none of the childhood cancer survivors with RIC developed symptomatic hemorrhages. Thus, we conclude that RIC are low-risk findings in brain MRI and the course is mainly benign.