伽玛刀照射正常脑组织引起的放射生物学变化

不同剂量伽玛刀照射猫的大脑皮层,照射后不同时期(1个月,3个月,半年,1年)分别观察其组织学变化。结果:160Gy,180Gy,200Gy伽玛刀术后1个月均引起脑组织坏死,200Gy产生的坏死灶较大;100Gy,70Gy3个月时未见组织坏死,1年时引起严重晚期反应;50Gy,40Gy引起晚期迟发放射反应;30Gy1年时仅局部细胞数量减少,20和10Gy无变化。30Gy可能是伽玛刀引起脑组织放射反应的阈剂量。     

伽玛刀治疗颞叶内侧癫痫疗效分析(附26例临床分析)

目的探讨伽玛刀治疗颞叶内侧癫痫的方法与疗效。方法2000年9月至2005年1月应用伽玛刀治疗颞叶内侧癫痫患者共26例,病程平均8年（4～42年）。治疗范围包括杏仁核,海马及部分海马旁回,50％等剂量曲线边缘剂量平均19Gy（15～20Gy）。结果随访0．7～5．03年,平均1．13年。26例患者中有10例发作完全消失,发作频率减少在50％以上的患者16例（62％）,在随访时间大于1．5年的9例患者中有6例发作完全消失,发作频率减少在50％以上的患者7例（77．8％）。所有患者中21例复查了核磁共振（MRI）,有14例在术后12个月前后出现局部水肿及血脑屏障破坏。全部病人未见头痛、记忆力下降、视束损伤等并发症。结论初步结果显示伽玛刀治疗颞叶内侧癫痫安全、有效,最终疗效评估仍需大量病例长期随访确定。     

Clinical Application of Gamma Knife Dose Verification Method in Multiple Brain Tumors : Modified Variable Ellipsoid Modeling Technique

Objective

The Leksell Gamma Knife® (LGK) is based on a single-fraction high dose treatment strategy. Therefore, independent verification of the Leksell GammaPlan® (LGP) is important for ensuring patient safety and minimizing the risk of treatment errors. Although several verification techniques have been previously developed and reported, no method has ever been tested statistically on multiple LGK target treatments. The purpose of this study was to perform and to evaluate the accuracy of a verification method (modified variable ellipsoid modeling technique, MVEMT) for multiple target treatments.

Methods

A total of 500 locations in 10 consecutive patients with multiple brain tumor targets were included in this study. We compared the data from an LGP planning system and MVEMT in terms of dose at random points, maximal dose points, and target volumes. All data was analyzed by t-test and the Bland-Altman plot, which are statistical methods used to compare two different measurement techniques.

Results

No statistical difference in dose at the 500 random points was observed between LGP and MVEMT. Differences in maximal dose ranged from -2.4% to 6.1%. An average distance of 1.6 mm between the maximal dose points was observed when comparing the two methods.

Conclusion

Statistical analyses demonstrated that MVEMT was in excellent agreement with LGP when planning for radiosurgery involving multiple target treatments. MVEMT is a useful, independent tool for planning multiple target treatment that provides statistically identical data to that produced by LGP. Findings from the present study indicate that MVEMT can be used as a reference dose verification system for multiple tumors.     

Gamma knife surgery for mesial temporal lobe epilepsy

PURPOSE: Gamma knife radiosurgery (GK) allows precise and complete destruction of chosen target structures containing healthy and/or pathologic cells, without significant concomitant or late radiation damage to adjacent tissues. All the well-documented radiosurgery of epilepsy cases are epilepsies associated with tumors or arteriovenous malformations (AVMs). Results prompted the idea to test radiosurgery as a new way of treating epilepsy without space-occupying lesions. METHODS: To evaluate this new method, we selected seven patients with drug-resistant "mesial temporal lobe epilepsy" (MTLE).The preoperative evaluation program was the one we usually perform for patients selected for microsurgery of TLE [video-EEG analysis of seizures, foramen ovale electrode recording, magnetic resonance imaging (MRI) positron emission tomography (PET) scan, neuropsychological testing]. In lieu of microsurgery, the amygdalohippocampectomy was performed by using GK radiosurgery. RESULTS: Morphologic (MRI) signs of destruction of the target took place at 9 months after GK surgery. Since the treatment day, the first patient has been seizure free. Seizure improvement came more gradually for the following patients, and complete cessation of seizures occurred around the tenth month (range, 8-15 months). MRI shows that the amygdaloentorhinohippocampal target was selectively injured. No significant side effect (except one case of homologous quadrantanopia) or morbidity and no mortality was observed. The current follow-up is 24-61 months, and all (but one) patients are seizure free. CONCLUSIONS: This initial experience proves clearly the short-to middle-term efficiency and safety of GK for MTLE surgery. These results need further confirmation of long-term efficiency, but the introduction of GK surgery into epilepsy surgery can reduce dramatically its invasiveness and morbidity.     

Leksell伽玛刀治疗原发性三叉神经痛46例报告

目的 评估伽玛刀在治疗原发性三叉神经痛中的作用与地位。方法 用1．5Tesla MRI行三堆超薄立体定位快速扫描。对46例原发性三叉神经痛病人行LEKSELL伽玛刀放射手术治疗,4mm准直器,中心刺量70～90Gy。靶点设定为三叉神经感觉根入桥脑处。结果 用标准咨询法对病人进行疗效评估。放射手术治疗前后疼痛按Ⅰ～Ⅳ级评分。Ⅰ级：无痛;Ⅱ级：偶发疼痛。不需用药;Ⅲ级。轻度疼痛。服药能控制;Ⅳ级。疼痛不能用药控制。46例病人中Ⅰ级26例(56．5％)。Ⅱ级9例(19．5％)。Ⅲ级7例(15．2％)。Ⅳ级4例(8．6％)。此外有4例病人疼痛复发。并接受第二次伽玛刀手术治疗。症状完全缓解。3例病人(6．5％)有迟发性的面部感觉丧失。无其他并发症发生。结论 伽玛刀放射外科手术是一种安全有效治疗三叉神经痛的高科技方法。应用性强。我们认为只要诊断成立。就可考虑施行伽玛刀手术治疗。     

Impact of the number of metastatic brain lesions on survival after Gamma Knife radiosurgery

Effectiveness of Gamma Knife radiosurgery (GKRS: Elekta AB, Stockholm, Sweden) for patients with metastatic brain disease and the prognostic factors influencing their survival were analyzed in a 5 year retrospective data analysis (July 2001 to June 2006). Kaplan–Meier survival curves were constructed using univariate and multivariate analyses with the respective salient prognostic factors. This study analyzed data on 330 patients with brain metastases who underwent GKRS. Lung carcinoma (55%) was the most common primary cancer followed by breast (17.8%), melanoma (9.4%), colorectal (4.8%) and renal (3.9%). The median survival for all patients was 8 months. Survival ranged from 13 months for breast metastases, 10 months for renal, and 8 months for lung to 5 months for colorectal and melanoma. Mean age of patients was 58.5 years (range 18–81). Melanoma patients were younger with a mean age of 49 and also had the highest number of lesions (3.8) when compared to patients with renal (2.5), lung (2.8), colorectal (3) and breast (3.6). When stratified according to the number of lesions patient survival was 8 months (one to three lesions), 7.5 months (four or five lesions) and 7 months (six lesions or more). Mean Karnofsky Performance Status score (KPS) was 77 and survival dropped significantly from 8 months to 4.5 months if KPS was less than 70. Survival improved with a KPS of 70 or more, regardless of the number of lesions treated. Selection of patients based on the number of lesions may not be justified. A prospective trial is required to further define the prognostic factors affecting survival.     

Acute necrosis after Gamma Knife surgery in vestibular schwannoma leading to multiple cranial nerve palsies

We discuss a rare acute complication after Gamma Knife therapy (Elekta AB, Stockholm, Sweden) in a single patient. A 52-year-old woman presented with vertigo, facial weakness and hearing loss emerging 48 hours following Gamma Knife radiosurgery for a right-sided vestibular schwannoma. Neurological examination 6 days after symptom onset showed right-sided facial palsy, spontaneous left-beating nystagmus and pathologic head-impulse testing to the right. Pure-tone audiogram revealed right-sided sensorineural hearing loss. A diagnosis of acute vestibulocochlear and facial neuropathy was made. Brain MRI demonstrated focal contrast sparing within the schwannoma, likely related to acute radiation necrosis. Acute multiple cranial neuropathies of the cerebellopontine angle after Gamma Knife treatment should raise suspicion of acute tissue damage within the schwannoma and should result in urgent MRI. Treatment with steroids may be considered based on accompanying swelling and edema.     

A single institutional outcome analysis of Gamma Knife radiosurgery for single or multiple brain metastases

Although Gamma Knife stereotactic radiosurgery (SRS) is widely used for metastatic brain tumors, optimal patient selection and treatment strategy continue to be investigated. The aim of this study was to provide treatment results with Gamma Knife SRS and to establish prognostic factors. Of the 54 patients treated from 1990 to 1997, 51 patients were evaluable. There were 28 males and 23 females, with a median age of 60 years. Median Karnofsky Index was 80. There were 19 non-small cell lung cancers, eight colon cancers, six renal cell cancers, five ovarian cancers, four gastric cancers, three breast cancers, and six others. Primary tumors were controlled in 33 patients, and extracranial tumors were absent in 25 patients. Sixty-eight metastatic brain tumors in 37 patients underwent SRS as an initial treatment for the brain metastasis. Brain metastasis was solitary in 32 patients. Conventional radiation was combined with SRS in 29 patients, 24 of whom received whole brain radiotherapy. Eight patients had some form of surgical resection. Median survival time was 7.4 months. Five-year actuarial survival and local control rates were 16 and 52%, respectively. Median duration time of keeping pretreatment quality of life was 6.9 months. On a multivariate analysis, uncontrolled primary tumor, combined conventional radiotherapy, and performance status were statistically significant prognostic factors. Four patients who underwent whole brain radiation developed low grade dementia.     

伽玛刀治疗颅内肿瘤的病理组织学研究

目的观察伽玛刀治疗颅内肿瘤的病理组织学变化,探讨伽玛刀治疗的放射生物学效应机制。方法对46例颅内肿瘤伽玛刀照射后的手术标本行光镜、电镜的病理形态学变化观察,并采用S-P法对上述肿瘤标本和10例正常脑组织血管标本行免疫组织化学染色,观察受照射肿瘤血管的CD34、α-SMA的表达,根据染色强度行对比分析。结果伽玛刀照射后的肿瘤细胞均有不同程度的凝固性坏死,肿瘤间质纤维化,血管内皮细胞肿胀、固缩、脱落,内皮增生,肿瘤血管扩张、充血,血管壁普遍出现增厚,管腔闭塞。可伴有炎性细胞浸润或出血。肿瘤的周边区域可观察到早期凋亡细胞。免疫组化的结果显示正常脑组织血管中CD34、α-SMA明显呈阳性,而受照射的肿瘤组织中CD34的反应性明显减少或呈阴性。α-SMA在大多数肿瘤组织中仍呈强阳性反应。结论伽玛刀治疗颅内肿瘤的放射生物学效应机制主要为肿瘤细胞的直接杀伤效应与血管效应的双重作用;伽玛刀照射诱导肿瘤细胞凋亡在伽玛刀治疗中起到一定作用。     

24例难治性颞叶癫痫手术患者病例分析

目的 了解难治性颞叶癫痫手术治疗的现状和预后效果.方法 回顾性分析2011年4月-2014年6月于淄博昌国医院经手术治疗且临床及随访资料完整的24例难治性颞叶癫痫手术患者,其中男14例,女10例.年龄16～44岁,平均(24.40±6.26)岁,平均病程(12.50±8.42)年.分析患者的临床特点和预后情况.结果 2...     

Fatal glioblastoma after Gamma Knife radiosurgery for arteriovenous malformation in a child

We describe a fatal case of glioblastoma multiforme that was induced by Gamma Knife radiosurgery (GKS; Elekta AB, Stockholm, Sweden) for an arteriovenous malformation (AVM). A 4-year-old girl presented with repeated convulsions. Imaging studies revealed an AVM located in the right thalamus. One year after initial symptoms, GKS was performed to obliterate the nidus. The maximum and marginal radiation doses were 32 and 16 Gy, respectively. Seventy months after GKS, the patient represented with severe headache. MRI showed a poorly demarcated tumor with heterogeneous gadolinium enhancement in the right thalamus and adjacent to the white matter of the temporal lobe. After a generalised convulsion, the patient deteriorated into a deep coma. CT scans showed severe brain swelling with intratumoral hemorrhage. An emergency craniotomy was performed, and the hematoma was removed. During this surgery, a tumor mass, which was found adjacent to the hematoma, was resected. Microscopic examination revealed glioblastoma multiforme. Despite intensive treatment, the patient died 1 month after surgery. A GKS-induced secondary tumor is a rare but serious complication. It is important to be aware of the adverse effects of GKS, including secondary neoplasms, before its clinical application, especially in young patients.     

The use of stereotactic radiosurgery to treat intractable childhood partial epilepsy

PURPOSE: Although conventional surgery is presently used to treat seizures of temporolimbic and neocortical origin, deep-seated lesions are often associated with morbidity. Stereotactic radiosurgery is a noninvasive procedure that effectively treats patients with vascular malformations and brain tumors, but its efficacy for epileptogenic foci is limited, especially in children. METHODS: Between 1995 and 1999, four candidates who had medically uncontrolled seizures and localized seizure foci were selected for stereotactic radiosurgery, with a mean age of 9.75 years at the time of surgery (range, 4-17 years). Seizure foci were identified on the basis of ictal and interictal video-EEG. Magnetic resonance (MR) images were obtained before and after surgery. Ictal single-photon emission computed tomography (SPECT) was performed by using stabilized hexamethyl-propyleneamine oxime (HMPAO; 300 microcuries/kg) with early injection after electrographic ictal onset. The clinical features of the patients are given. All radiosurgical procedures were performed with the gamma knife unit with the Leksell stereotactic frame, stereotactic MRI imaging, and the Gamma Plan workstation. Seizure outcome was scored according to Engel's classification. RESULTS: Two patients had hypothalamic hamartoma (HH), and two had neocortical epilepsy. At mean follow-up of 39.2 months (range, 26-69 months), two patients were seizure free, one with a HH and one with a suggestive developmental tumor in the insular cortex by MRI findings. The other patient with HH had 90% reduction of seizures. One patient with a widespread seizure focus that involved the motor strip was unimproved. The two patients with HH also exhibited markedly improved neurobehavioral status after surgery. There were no significant complications of radiosurgical therapy. CONCLUSIONS: Our findings suggest that gamma knife surgery is a potentially valuable treatment modality for children with medically intractable epilepsy due to a well-localized seizure focus that is difficult to excise by conventional techniques or for whom they are deemed unsuitable. More widespread application in childhood epilepsy should be investigated in larger series.     

Radiosurgery for epilepsy: clinical experience and potential antiepileptic mechanisms

Stereotactic radiosurgery, well established in the noninvasive treatment of focal lesions that are otherwise difficult to access through open surgery, is an emerging technology in the treatment of focal epileptic lesions. Recent studies suggest that seizures from hypothalamic hamartomas and mesial temporal lobe epilepsy remit at clinically significant rates with radiosurgery, but large variations among different studies have raised questions about appropriate treatment protocols and mechanisms. Proposed anticonvulsant mechanisms include neuromodulatory effects or ischemic necrosis of epileptic tissue. An ongoing trial that directly compares efficacy, morbidities, and cost of radiosurgery versus open surgery for mesial temporal lobe epilepsy is underway.     

顽固性癫痫的组合手术治疗

目的对部分顽固性癫痫病人，在严格充分的术前评价之后．依据结果将几种手术方式适当的组合使用，并对其临床效果进行评价。方法对同济大学东方医院神经外科收治的116例顽固性癫痫中的25例病人施行联合手术的治疗方法。发作形式为全身强直一阵挛性发作、复杂部分性发作及失神发作等，其中有14例存在两种发作形式。术前均服过多种抗癫痫药．病程后期同时服用2～3种抗癫痫药。25例病人术前均行24h脑电监测及头颅MRI检查．有19例术前行硬膜下皮层电极和深部电极检测，其中1例行头颅PET检查。手术在皮层脑电及深部电极监测下进行。13例行额颢开颅，颞前叶及海马、杏仁核切除＋额部部分区域的软膜下横切术（MST），其中7例附加胼胝体前部切开术；11例行额部开颅，额部软化灶切除＋运动区MST，其中2例附加胼胝体前部切开术；1例行双侧枕顶部开颅，左枕叶萎缩皮层切除＋胼胝体后部切开＋右侧顶枕的MST。结果术后无死亡及严重并发症。术后抗癫痫药物使用减少，术后23例服用一种抗癫痫药，2例服用两种抗癫痫药。术后随访6～12个月，17例手术效果为Engel 1级，4例为Engel2级，4例为Engel3级。40岁以下的患者手术后癫痫控制的可能性显著大于40岁以上者（P〈0．05）；病程在10年以下的患者术后癫痫无发作的可能性显著大于10年以上者（P〈0．05）。头颅MRI上有无明显的结构异常对病人的预后没有影响（P〉0．05）。结论在严格术前评价的前提下，尤其是在有精通神经电生理知识的神经外科医生综合分析下，采用多种手术方式组合治疗顽固性癫痫效果显著。     

Mask-based immobilization in Gamma Knife stereotactic radiosurgery

The Gamma Knife Icon (Elekta AB, Stockholm) is a cobalt-based stereotactic radiosurgery (SRS) unit to support the use of a thermoplastic mask in lieu of a rigid frame, using an onboard cone-beam CT (CBCT) and an intrafraction motion management system (IFMM). We retrospectively reviewed 124 patients treated with Gamma Knife SRS from January 2018 to December 2019 at our institution using a mask-based immobilization system. Patient and treatment characteristics were collected and summarized as well as interfraction shifts and treatment-related outcomes. This dataset includes 124 patients with an associated 358 intracranial tumors. Twenty-four patients presented with primary brain tumors, which included 14 meningiomas and 10 other histologies, with 100 patients having brain metastases. Sixty tumors were post-operative, while 298 were intact. The median dose for primary tumors was 25 Gy in 5 fractions. Median doses to metastases were 20 Gy in 1 fraction, 27 Gy in 3 fractions, and 25 Gy in 5 fractions. Median interfraction CBCT shifts were submillimeter. Median patient follow-up was 6.28 months. 91% of patients with metastases maintained local control. Our early clinical experience has demonstrated limited toxicity profiles and high patient tolerance, which suggests that mask-based Gamma Knife SRS provides a safe alternative option for frameless SRS. Patients with large target volumes where fractionation is preferred or with small target volumes in non-eloquent areas can be considered for this approach. Response rates are encouraging, and continued follow-up is necessary to investigate long-term control and survival.     

Clinical Outcomes of Gamma Knife Radiosurgery for Metastatic Brain Tumors from Gynecologic Cancer : Prognostic Factors in Local Treatment Failure and Survival

ObjectiveBrain metastases in gynecologic cancer (ovarian, endometrial, and cervical cancer) patients are rare, and the efficacy of Gamma Knife Radiosurgery (GKRS) to treat these had not been evaluated. We assessed the efficacy of GKRS and prognostic factors for tumor control and survival in brain metastasis from gynecologic cancers.MethodsThis retrospective study was approved by the institutional review board. From May 1995 to October 2012, 26 women (mean age 51.3 years, range 27–70 years) with metastatic brain tumors from gynecologic cancer were treated with GKRS. We reviewed their outcomes, radiological responses, and clinical status.ResultsIn total 24 patients (59 lesions) were available for follow-up imaging. The median follow-up time was 9 months. The mean treated tumor volume at the time of GKRS was 8185 mm³ (range 10–19500 mm³), and the median dose delivered to the tumor margin was 25 Gy (range, 10–30 Gy). A local tumor control rate was 89.8% (53 of 59 tumors). The median overall survival was 9.5 months after GKRS (range, 1–102 months). Age-associated multivariate analysis indicated that the Karnofsky performance status (KPS), the recursive partitioning analysis (RPA) classification, and the number of treated lesions were significant prognostic factors for overall survival (HR=0.162, p=0.008, HR=0.107, p=0.038, and HR=2.897, p=0.045, respectively).ConclusionGKRS is safe and effective for the management of brain metastasis from gynecologic cancers. The clinical status of the patient is important in determining the overall survival time.     

Early- and late-onset complications of the ketogenic diet for intractable epilepsy

PURPOSE: This study was undertaken to evaluate the exact limitations of the ketogenic diet (KD) and to collect data on the prevention and management of its risks. METHODS: Patients (129) who were on the KD from July 1995 to October 2001 at our epilepsy center were assessed in the study. Early-onset (within 4 weeks of the commencement of the KD until stabilization) and late-onset complications (occurring after 4 weeks) were reviewed. RESULTS: The most common early-onset complication was dehydration, especially in patients who started the KD with initial fasting. Gastrointestinal (GI) disturbances, such as nausea/vomiting, diarrhea, and constipation, also were frequently noted, sometimes associated with gastritis and fat intolerance. Other early-onset complications, in order of frequency, were hypertriglyceridemia, transient hyperuricemia, hypercholesterolemia, various infectious diseases, symptomatic hypoglycemia, hypoproteinemia, hypomagnesemia, repetitive hyponatremia, low concentrations of high-density lipoprotein, lipoid pneumonia due to aspiration, hepatitis, acute pancreatitis, and persistent metabolic acidosis. Late-onset complications also included osteopenia, renal stones, cardiomyopathy, secondary hypocarnitinemia, and iron-deficiency anemia. Most early- and late-onset complications were transient and successfully managed by careful follow-up and conservative strategies. However, 22 (17.1%) patients ceased the KD because of various kinds of serious complications, and four (3.1%) patients died during the KD, two of sepsis, one of cardiomyopathy, and one of lipoid pneumonia. CONCLUSIONS: Most complications of the KD are transient and can be managed easily with various conservative treatments. However, life-threatening complications should be monitored closely during follow-up.