Gamma Knife radiosurgery for cavernous malformation
Stereotactic radiosurgery (SRS) is a therapeutic option for repeatedly hemorrhagic cavernous malformations (CMs) located in areas deemed to be high risk for resection. During the latency period of 2 or more years after SRS, recurrent hemorrhage remains a persistent risk until the obliterative process has finished. The pathological response to SRS has been studied in relatively few patients.
Hu et al. retrospectively reviewed the clinical and radiological data of 53 patients with CMs of basal ganglia and thalamus who underwent GKRS at West China Medical Center between May 2009 and July 2018. All patients suffered at least once bleeding before GKRS. The mean volume of these lesions was 1.77 cm3, and the mean marginal dose was 13.2 Gy. After treatment, patients were followed to determine the change in symptom and hemorrhage event.
The mean follow-up period was 52.1 months (6.2-104.3 months). The calculated annual hemorrhage rate (AHR) was 48.5% prior to GKRS and 3.0% after treatment (p < 0.001). The Kaplan-Meier analysis revealed that 2-, 3-, and 5-year hemorrhage-free survival were 88, 80.9, and 80.9%, respectively. Preexisting symptoms were resolved in 11 patients, improved in 14, and stable in 5. Only 2 patients (3.8%) developed new neurological deficit.
This study suggests that AHR after GKRS was comparable to the recorded AHR of natural history (3.1-4.1%) in previous studies. GKRS is a safe and effective treatment modality for CMs of basal ganglia and thalamus. Considering the relative insufficient understanding of natural history of CMs, future study warrants longer follow-up 1)
9 studies are included in this meta-analysis. The overall RR of hemorrhage rate of pre-GKRS and post-GKRS is 6.08(95% CI: 5.04-7.35). The overall RR is 3.03(95% CI: 2.65-4.11) between the hemorrhage rate of pre-GKRS and the first 2 years of post-radiosurgery, and the overall RR is 12.13 (95% CI: 1.73-85.07) comparing pre-GKRS with 2 years after GKRS. There is no significant difference of the hemorrhage rate between the first 2 years of post-radiosurgery and 2 years after GKRS (RR =2.81, 95% CI: 0.20-13.42). The neurological deficiency is the commonest radiosurgery related complications.
Patients with cerebral CMs, especially who were deep seated and surgically inaccessible, seems to benefit from GKRS due to a reduction of annual hemorrhage rate in the first 2 years, and after that time, despite of a number of cases that suffer from negative side effects of radiation 2).
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 3).
Shin et al. aimed to gain insight into the effect of SRS on CM and to propose possible mechanisms leading to recurrent hemorrhages following SRS.
During a 13-year interval between 2001 and 2013, bleeding recurred in 9 patients with CMs that had been treated using Gamma Knife surgery at the authors’ institution. Microsurgical removal was subsequently performed in 5 of these patients, who had recurrent hemorrhages between 4 months and 7 years after SRS. Specimens from 4 patients were available for analysis and used for this report.
Histopathological analysis demonstrated that vascular sclerosis develops as early as 4 months after SRS. In the samples from 2 to 7 years after SRS, sclerotic vessels were prominent, but there were also vessels with incomplete sclerosis as well as some foci of neovascularization.
Recurrent bleeding after SRS for CM could be related to incomplete sclerosis of the vessels, but neovascularization may also play a role 4).
From 1994 to 2001, 92 patients with 114 CMs were treated by GKS and then followed up for 2-8 years (mean 4.1+/-1.9). We analyzed the MRI features of CMs bleeding, efficacy of GKS, and the complications of treatment. Six pathological specimens after radiosurgery (1 from our group, 5 from other centers) were also assayed.
Among 43 patients who were treated by GKS to control their epilepsy, epileptic paroxysm was alleviated in 36 patients (83.7%), including 12 (27.9%) seizure-free. Rebleeding was confirmed in 9 patients (9.8%) by neuroimage, one of whom died. Transient symptomatic radiation edema occurred in 7 cases (7.6%) within 6-12 months after radiosurgery, and one patient underwent open surgery for cerebral decompression. The main pathological changes of cavernoma were coagulation necrosis and the vessels obliterated gradually after radiosurgery.
It is feasible to treat small and surgically high risk CMs by radiosurgery. The treatment has to be prudent in an acute bleeding and symptomatic progression. Optimal treatment timing and dose planning are prerequisites to reduce radiation-related complications. GKS is safe and effective to control the epilepsy caused by CMs, and also to bring down the rebleeding rate after a latency interval of several years 5).