1, mechanism and treatment status
In the last 60-70 years, epilepsy surgery has been developed and has become an important branch of functional neurosurgery, with improved surgical outcomes and fewer complications than before, but still not completely avoided. surgery was 5.4%, of which 3.03% were temporary and 2.33% were permanent. Therefore, further improving the safety of surgery and reducing complications are still major issues in the surgical treatment of epilepsy.
Over the past 40 years since the introduction of radiosurgery, the means of focused irradiation has gradually been applied to the field of epilepsy treatment. The treatment of epilepsy by radiation irradiation began with Talairach (1974) in France, who used radioisotope 91 iridium pellets implanted in the amygdala-hippocampus of 44 patients with epilepsy from 1955 to 1975 and found a reduction in seizures after several years of observation. The epileptogenic effect of epileptic foci could be inhibited by external irradiation and synaptic loss of neuronal dendrites in epileptogenic foci was observed. monnier observed in experiments on the effect of radiation on nerve cells that 10Gy irradiation produced inhibition of cortical neuronal activity. Mori Y (2000) et al. reported the efficacy of stereotactic radiosurgery in the treatment of an animal model of hippocampal epilepsy. The animal model was established using stereotactic surgery by injecting red alginate into the hippocampus of rats, and then treated with 20Gy, 40Gy, 60Gy, and 100Gy irradiation, respectively, and achieved good efficacy. Chen (2001) and others in the United States reported the use of electrical stimulation of the rat hippocampus to establish an animal model of epilepsy, and then applied the gamma knife 4mm collimator to give a central dose of 20Gy and 40Gy irradiation, respectively, and observed more than 10 months, the seizures and electrophysiological performance of rats significantly improved. The possible mechanisms of gamma knife treatment of epilepsy are currently considered to be.
(1) Blockade of epileptogenic nerve conduction.
(2) The doctrine of high sensitivity of epileptic neurons to radiation.
(3) Radiosurgery can cause a reduction in epileptogenic neurons and decreased excitability.
(4) radiosurgery can produce radionecrosis of the epileptogenic foci, similar to the antiepileptic effect achieved by lesion excision.
With the clinical application of gamma knife, secondary epilepsy has also been controlled in the treatment of cerebral AVM and benign glioma and cavernous hemangioma, thus drawing attention and beginning to explore its use in the treatment of refractory epilepsy due to invisible lesions. In the last decade, with the rapid development of electrophysiology and neuroimaging and the clinical application of many new technologies, the localization of epileptogenic foci has become more and more precise and gradually developed in the direction of three-dimensional and non-invasive. The conditions for the application of radiosurgery treatment are also becoming mature. The focus of gamma knife treatment for epilepsy began to shift to primary epilepsy and is now a new technique in the surgical treatment of epilepsy along with vagus nerve electrical stimulation and deep electrical stimulation.
Lindquist (1991) reported that 59 of 247 patients with AVM treated between 1970 and 1984 had seizures, and 52 seizures stopped after treatment. 15 of 72 pediatric patients with AVM treated by Gerszten et al. had seizures, and 13 seizures stopped after treatment without antiepileptic drugs. 19 patients with epilepsy with medial temporal lobe tumors treated with Gamma Knife from 1992 to 1997 were given marginal doses of 12-30 Gy (mean 17.3Gy) and followed up for 1.7-9.7 years (mean 6.5 years), 11 cases (57.9%) achieved Engle’s score grade I and II, 7 cases (36.8%) grade III, and 1 case ( 5.3%) were ineffective, and 11 (58%) of them showed radiological reactions visible on MRI.
In 1988, Barcia-salora in Spain reported that an animal model of epilepsy was made by embedding cobalt oxide powder in the left subdural frontal lobe of a cat, and then irradiated with a gamma knife at 10 Gy, resulting in complete cessation of seizures. In the same year, he reported the treatment of 6 epileptic patients with gamma knife and obtained satisfactory results. 1993 and 1994, he summarized 11 patients treated from 1982 to 1991 and their follow-up results. He used EEG, cortical electrodes and deep electrodes, CT, MRI localization, and a 10 mm aperture collimator with an irradiation dose of 10-20 Gy. As a result, the seizures stopped in 5 cases immediately after treatment and improved in the other 5 cases. Most of these patients showed results from 3 to 12 months after treatment, and stable results from 3 months to 4 years later. After long-term (average 7.5 months) follow-up, no complications occurred in any of the cases. Therefore, he concluded that the advantages of gamma knife treatment for epilepsy are safety, no complications, and small low-dose irradiation without brain necrosis.Whang et al. reported 31 patients with refractory epilepsy treated with gamma knife between 1990 and 1995, with seizure duration ranging from 1 to 25 years, with a mean of 11.6 years. The target volume averaged 1 cm3 with a marginal dose of 22.9 (10-50) Gy and a 45-70% isodose curve envelope. At follow-up, 12 patients had a good outcome (Engle’s score grade I) and three of them discontinued their antiepileptic drugs. In addition, there was a reduction in seizure frequency in two cases (Engle’s scale II and III) and no change in seizure frequency in the remaining nine cases (scale IV). Smith (2000) reported 53 cases of epileptic patients treated with gamma knife and suggested that magnetic source imaging with MRI and magnetoencephalography superimposed could help to locate the epileptogenic focus accurately. Zhou WJ (2001) reported that two patients with intractable epilepsy localized in the frontal lobe were treated with Gamma Knife and were followed up for 5 years. One case had only mild seizures at 6 and 21 months after surgery, and the other case had one seizure at 7 and 10 months after surgery, with no clinical adverse effects.
Surgical treatment of epilepsy currently has better efficacy mainly in temporal lobe epilepsy, and Ryvlin (2003) summarized the surgical methods including gamma knife for temporal lobe epilepsy since 1990, and the percentage of completely disappeared disabling seizures after treatment was 70%. Regis J (1994) in France first reported the treatment of medial temporal lobe epilepsy (MTLE) with the gamma knife, and in 1999 summarized seven patients, all of whom were targeted with the amygdala-hippocampus, and the gamma knife conformal radiation, with a volume of 7 cm3, was the largest target used at that time to treat functional disorders with the gamma knife. The seizures of the first patient immediately stopped, and the rest of the patients gradually reduced within 10 months after treatment, after 19-61 months of follow-up, except for one case of occasional seizures, the other five cases completely disappeared, the whole group of patients finally only two cases need to take a small amount of anti-epileptic drugs, the rest of all stop. MRI-enhanced scans revealed necrotic foci-like changes in the target area at 10 months after treatment, and FDG-PET showed hypometabolic changes in the anterior hippocampus, and at months 24, 25, 31, 37, and 49, MRI showed that the necrotic foci gradually disappeared, and finally only medial temporal lobe atrophy was seen, and peripheral enhancement and edema shadows disappeared. In 2000, he continued to summarize the results of treatment in 25 patients. Of the 16 patients followed up for more than 24 months, 13 had complete cessation of seizures and 2 had remission, and MRI showed target area-like ring enhancement shadows and peripheral edema-like changes 7-12 (average 11) months after treatment. The MRI gradually returned to normal.
Kawai et al. reported 2 cases of medial temporal lobe epilepsy that were ineffective after gamma knife treatment with 18 Gy (50% isodose curve), and the seizures disappeared after anterior temporal lobectomy at 30 and 18 months postoperatively, respectively. And another author in the same unit, Kurita et al, also reported a patient with complex partial seizures in the medial temporal lobe with hemangioma, whose seizures ceased after administration of 18 Gy marginal dose treatment. Reported 26 patients with medial temporal lobe epilepsy treated with Gamma Knife with a follow-up of 0.7 to 5.03 years with a mean of 1.13 years. There was complete disappearance of seizures in 10 patients and reduction in seizure frequency by 50% or more in 16 patients (62%), and complete disappearance of seizures in 6 of the 9 patients with a follow-up time greater than 1.5 years and reduction in seizure frequency by 50% or more in 7 patients (77.8%).
In the Regis report a marginal dose of 25 Gy (50% isodose curve) was used, containing a mean target area volume of 6.5 cm3 (range 6.25 to 6.9 cm3). In the 26 patients reported by the author, considering the safety of the optic tract nerve, the marginal dose was a mean of 19 Gy (50% isodose curve) and the volume contained by 18 Gy averaged 6.01 cm3 (range 3.90 to 8.87 cm3). 21 of these patients had MRI reviewed and a transient radioactive blood-brain barrier disruption was seen in 14 cases, appearing around 12 months postoperatively, with no adverse complaints. Gradual recovery was seen on more prolonged reexamination. All patients had no complications such as headache, memory loss, or damage to the visual beam, and there were no deaths.
In addition, Cmelak (2001) et al. reported a case of medial temporal lobe epilepsy treated with a marginal dose of 15 Gy (60% isodose curve) that was ineffective, and the seizures disappeared after a temporal lobectomy including the amygdala and hippocampus 1 year later, which was considered ineffective due to the low dose.
The author Grabenbauer also reported 11 patients with temporal lobe epilepsy treated with isocentric linear gas pedal (X-blade) fractionated irradiation with marginal doses of 21 Gy (3 Gy per session, 7 sessions) and 30 Gy (2 Gy per session, 15 sessions), with a 46% reduction in mean seizure frequency at 18-month follow-up, including 7 cases with reduced seizure intensity and 5 cases with reduced seizure duration.
Gamma knife is effective in treating medial temporal lobe epilepsy with less injury and fewer complications than conventional temporal lobe, amygdala, and hippocampal resections. However, the optimization of treatment methods and dose planning is still imperfect, and the final treatment specification and evaluation of efficacy still need a large number of cases and long-term follow-up to determine.
2.Indications
Gamma knife treatment belongs to the surgical treatment, but compared with the open surgery method, its risk is small, less complications, and more acceptable to patients. According to current experience, based on the premise of refractory epilepsy, the following conditions are more suitable.
(1) Simple medial temporal lobe epilepsy.
(2) Focal epilepsy, with a single epileptogenic focus and clear localization, and the treatment area should not be larger than 3 cm.
The determination of the epileptogenic focus can be measured using the following 4 indicators.
(1) clinical data, seizure aura, seizure description, and physical signs.
(2) Anatomical examination, CT, MRI, etc.
(3) Electrophysiological examination, conventional EEG, dynamic EEG, video EEG, 128-lead EEG dipole analysis, intracranial EEG, etc.
(4) Brain function tests, SPECT, PET, MRS, MEG, etc. At least 3 indicators should be positive and the sites match, of which electrophysiology is a must.
According to the author’s experience, at present, for the localization of temporal lobe epilepsy, it is difficult to clarify whether the origin of seizures is the hippocampal region of the amygdala in the medial temporal lobe or the neocortex in the lateral temporal lobe by non-invasive means. The common view in the past was that MRI demonstration of hippocampal sclerosis was an important indication of medial temporal lobe epilepsy, and the current tendency is to consider hippocampal sclerosis as a secondary manifestation of lateral temporal lobe epilepsy. Therefore, in 2004, the author started to use minimally invasive implantation of subdural and deep electrodes to monitor the EEG origins during seizures, which effectively distinguishes between medial and lateral temporal lobe origins and also identifies whether pseudo-temporal lobe epilepsy is transmitted from the frontal or parieto-occipital regions.
For focal seizures of convex brain origin, 128-conductance dipole analysis or magnetoencephalography has some reference value for gamma knife treatment because it can be fused with MRI for imaging, but it should be analyzed comprehensively with other examination means, and intracranial electrodes should be done to verify the origin of seizures when available.
3, contraindications
Gamma knife treatment, although using a lower dose of irradiation, but still may damage the brain, and there is still little experience, the following cases are not suitable for gamma knife treatment: (1) epileptiform discharges are extensive and diffuse; (2) localization is not clear; (3) the scope of the epileptogenic foci greater than 4cm.
4. Methods
(1) Medial temporal lobe epilepsy
The Y-axis can be anteriorly low and posteriorly high when fixing the head frame, and try to make the basal ring parallel to the hippocampal long axis. The MRI scan includes T1 image axial and coronal position, and the target contour is outlined in the coronal position. The treatment area should include the amygdala, hippocampus, and parahippocampal gyrus. The treatment volume should be 7-12 cm3 and the limbic dose should be 17-24 Gy. Special attention should be paid to the brainstem limbic dose below 14 Gy and the optic cross and optic bundle limbic dose below 10 Gy.
(2) Cortical epileptogenic foci
Since the lesion is located on the surface of the cortex, attention should be paid to the appropriate adjustment when fixing the head frame to ensure that the target is within the effective coordinates. The target area should be within 3cm in diameter, and the marginal dose should be 10-15Gy, and the scalp dose should be less than 7Gy.
5.Efficacy assessment
Gamma knife treatment of epilepsy is gradual, so the traditional surgical efficacy assessment criteria are not suitable. Some patients can stop seizures after treatment, most patients need several months to gradually take effect, and some patients will experience a period of exacerbation before stopping seizures. Therefore, the assessment of efficacy can be done using the general surgical criteria, but should be started after one year of treatment.