Patient population
From 2003 to 2018, there were 121 cases of intracranial cavernoma blindly approved by the two independent neurosurgeons excluding the in-charge neurosurgeon for the GKRS based on the patients’ medical records and imaging findings at the Central Bureau of Health Insurance, Taichung, Taiwan, to determine whether GKRS was the appropriate treatment. The approval criteria was based on the consensus of Taiwan Neurosurgical Society on for GKRS including one or more of the following: recurrence of cavernoma after craniotomy, nidus volume less than 20cc or maximum diameter less than 3.5cm, vulnerable location for the nidus removal, severe illness inappropriate for general anesthesia, or KPS>70. Finally, there were 105 of 121 (86.7%) cases approved for Gamma Knife treatment. There were 11 cases lost to follow up, and, as such, 94 (89.5%) cases were included in this study. The study was approved by the ethical committee of Taichung Veterans General Hospital on record No. CG 18080
Radiosurgical Technique
After the patient had received a local anesthetic agent, the Leksell G head frame was affixed to the head, and the patient was monitored for blood pressure, oxygenation, and electrocardiography. All patients were treated with a Leksell Gamma Knife model D (Elekta AB) by a team consisting of a neurosurgeon, neuroradiologist, radiation oncology, and medical physicist. All patients underwent GKRS with low margin dosage of 11-12 Gy prescribed to nidus at the isodose line of 50% to 60%. Radiosurgery dose plans, with single or multiple isocenters, were created, and the targeted margin of the cavernoma was considered to be the region characterized by mixed signal change within the T2-weighted signal-defined hemosiderin ring [33].
Imaging Technique
The target lesions were typically imaged using a 1.5-T MR imaging unit (GE Medical Systems). Target localization was performed using T1-weighted, fast-spin-echo T2-weighted, spoiled-gradient recalled, and time-off light imaging. Additional T1-weighted, spoiled-gradient recalled, and time-of-flight sequences were also obtained after administration of gadolinium (Gd). The axial volume acquisition of 256 × 256 matrices was divided into 1-mm thickness without a gap. All patients gave informed consent to receive a Gd injection in accordance with Taiwan guidelines concerning Gd administration during MR imaging examinations.
Clinical follow up and assessment of Life quality
The patients received regular follow up at 3-6 month intervals after GKRS including neurological examination and record of frequency, intensity and drug dosage in patients with a seizure history. SF-36 is a well-validated instrument for measuring quality of life (QOL) [34]. It covers 8 domains including physical function (PF), role limitation due to a physical problem (RP), bodily pain (BP), general health (GH), vitality, social functioning (SF), role limitation due to an emotional problem (RE), and mental health (MH). In this study, BP was specifically limited to headache and facial pain, and these were clearly described for the participants. In general, the physical component summary covered PF, RP, BP, and GH, whereas the mental component summary included vitality, SF, RE, and MH. Scores on the SF-36 scale range from 0 to 100, with higher scores indicating better condition. The QOL data were collected prior to GKRS and at last out-patient follow-up. The Karnofsky Performance Score (KPS) spans from 100 to 0, where 100 is "perfect" health and 0 is death [35]. KPS was also collected by the clinical team before GKRS and at last follow up.
Imaging Follow-Up
All patients underwent routine MR imaging examinations 6–12 months after GKRS. More specifically, T1-weighted images were obtained with or without administration of Gd, and T2-weighted images were obtained to evaluate whether there were any adverse treatment effects. If patients experienced new neurological deficits (increased seizure frequency, impairment sensory of motor function), they underwent additional imaging examinations at the time of newly neurological deficits to evaluate for radiologic changes associated with these clinical changes. The assessment of volume alteration was based on our previous investigation with volume enlargement by 20% defined as increase, volume reduction by 20 % defined as decrease, and volume changes of less than 20% from baseline defined as stable [36].
Statistical Analysis
Descriptive statistics were computed using standard methods to calculate mean± standard deviation or median values with ranges. Factors contributing to seizure frequency, imaging alteration, neurological outcome, and quality of life that were assessed by the Mann-Whitney test, Chi-Square test, and Fisher's Exact test. Logistical regression testing was used for the assessment of risk factors related to control of seizure, new neurological deficits and improvement in QOL. A p value < 0.05 was considered significant.