BACKGROUND AND OBJECTIVES:Brain arteriovenous malformations (BAVMs) in hereditary hemorrhagic telangiectasia (HHT) differ genetically and structurally from sporadic BAVMs. However, the efficacy and safety of stereotactic radiosurgery (SRS) for HHT-BAVMs remain unclear. This study aimed to evaluate the outcomes of SRS for HHT-BAVMs in the largest cohort to date. METHODS:We retrospectively analyzed 31 patients with definite HHT (Curaçao criteria 3 and 4 or genetically confirmed) who underwent SRS for 63 BAVM nidi at 12 Gamma Knife centers from 2003 to 2021. Clinical and treatment characteristics were collected, and outcomes were evaluated. Kaplan-Meier analysis was used to estimate cumulative obliteration rates. Cox proportional hazards models identified factors associated with nidus obliteration. RESULTS:The median age was 28 years; the median follow-up was 74 months (range, 6-230 months). Most lesions (95%) were Spetzler-Martin grade I or II. The median nidus size was 9.0 mm. The median target volume was 0.40 mL (range, 0.02-13.8 mL), and the median marginal dose was 20.0 Gy (range, 14.9-24.0 Gy). Obliteration was confirmed in 46 nidi (27 by digital subtraction angiography). The 5- and 7-year cumulative obliteration rates were 61.9% and 81.2%, respectively. The median time to obliteration was 40 months. Multivariate analysis showed that smaller nidus size (P = .008) and higher marginal dose (P = .004) were independent predictors of obliteration. No symptomatic hemorrhages from BAVMs occurred during follow-up. Radiation-induced changes were observed in 23.8% of nidi; only 6.5% of patients experienced transient symptoms. Functional outcomes remained stable in 93.5% of patients, with 87.1% maintaining modified Rankin Scale 0 to 1 at the last follow-up. One patient died from non-AVM-related hemorrhage, and 2 patients developed de novo AVMs during follow-up. CONCLUSION:SRS for HHT-BAVMs achieved high obliteration rates with minimal morbidity. Given the low rate of hemorrhage and favorable functional outcomes, SRS could be considered a safe and effective treatment option for this unique patient population.

Stereotactic radiation therapy, including stereotactic radiosurgery, is a well-established and effective treatment for cerebellopontine angle tumors such as meningiomas, vestibular schwannomas, trigeminal and jugular foramen schwannomas, and glomus tumors. It offers high rates of tumor control while preserving neurological function, particularly in tumors smaller than 3 cm, which are ideal candidates for stereotactic radiosurgery. Large tumors or those extending beyond the skull base can also be managed effectively using fractionated stereotactic radiation therapy. As such, a multidisciplinary approach that combines surgical resection with stereotactic radiation therapy is a valuable strategy, especially when functional preservation is a key therapeutic goal.

OBJECTIVE:Brain metastasis is rare in ovarian cancer patients. The results of Gamma Knife radiosurgery (GKRS) for the treatment of patients with brain metastases from ovarian cancer were retrospectively analyzed to derive the efficacy and prognostic factors for survival and local tumor control. Further histopathological analysis was also performed.METHODS:The authors retrospectively reviewed the medical records of 118 patients with 566 tumors who had undergone GKRS at the 10 GKRS institutions in Japan.RESULTS:After the initial GKRS, the median overall survival time was 18.1 months. Multivariate analysis showed that uncontrolled primary cancer (p = 0.003) and multiple intracranial metastases (p = 0.034) were significant unfavorable factors. Ten patients died of uncontrolled brain metastases at a median of 17.1 months. The 6-, 12-, and 24-month neurological death rates were 3.2%, 4.6%, and 11.9%, respectively. The 6-, 12-, and 24-month neurological deterioration rates were 7.2%, 13.5%, and 31.4%, respectively. The 6-, 12-, and 24-month distant brain control failure rates were 20.6%, 40.2%, and 42.3%, respectively. Median tumor volume was 1.6 cm3 and marginal dose was 20 Gy. The 6-, 12-, and 24-month local tumor control rates were 97.6%, 95.2%, and 88.0%, respectively. Peritumoral edema (p = 0.043), more than 7-cm3 volume (p = 0.021), and prescription dose less than 18 Gy (p = 0.014) were factors that were significantly correlated in local tumor control failure. Eight patients had symptomatic radiation injury. The 6-, 12-, and 24-month GKRS-related complication rates were 3.3%, 7.8%, and 12.2%, respectively. Primary ovarian cancer was histopathologically diagnosed for 313 tumors in 69 patients. Serous adenocarcinoma was found in 37 patients and other types in 32 patients. Median survival times were 32.3 months for the serous type and 17.4 months for other types after initial GKRS. Patients with serous-type tumors survived significantly longer than patients with other types (p = 0.039). The 6-, 12-, and 24-month local tumor control rates were 100%, 98.8%, and 98.8%, respectively. Serous-type tumors were a significantly good prognosis factor for local tumor control after GKRS (p = 0.005).CONCLUSIONS:This study established a relationship between the efficacy of GKRS treatment for brain metastases and the histological type of primary ovarian cancer. GKRS for ovarian cancer brain metastasis can provide satisfactory survival and local control, especially in cases of serous adenocarcinoma.

We report the case of a 29-year-old man who presented with a sudden headache. Computed tomography showed a small intraventricular hemorrhage in the left lateral ventricle. Cerebral angiograms suggested rupture of a coexisting feeder aneurysm in the left temporal cerebral arteriovenous malformation (AVM). The left proximal middle cerebral artery, a major feeding artery, was occluded near the AVM, with development of abnormal blood supply, such as in moyamoya-like vessels to the nidus. After endovascular embolization of the coexisting feeder aneurysm and feeding arteries, the patient underwent volume-staged Gamma Knife radiosurgery (GKS). Follow-up angiograms performed 4.5 years after the last GKS confirmed complete disappearance of the AVM. Around 4.8 years after GKS, the patient required surgical intervention to develop delayed cyst formation; however, the postoperative course was uneventful.

BACKGROUND AND PURPOSE:To assess the long-term outcomes of intracranial dural arteriovenous fistula (DAVF) treated with stereotactic radiosurgery (SRS) alone or embolization and SRS (Emb-SRS) and to develop a grading system for predicting DAVF obliteration.METHODS:This multi-institutional retrospective study included 200 patients with DAVF treated with SRS or Emb-SRS. We investigated the long-term obliteration rate and obliteration-associated factors. We developed a new grading system to estimate the obliteration rate. Additionally, we compared the outcomes of SRS and Emb-SRS by using propensity score matching.RESULTS:The 3- and 4-year obliteration rates were 66.3% and 78.8%, respectively. The post-SRS hemorrhage rate was 2%. In the matched cohort, the SRS and Emb-SRS groups did not differ in the rates of obliteration (P=0.54) or post-SRS hemorrhage (P=0.50). In multivariable analysis, DAVF location and cortical venous reflux (CVR) were independently associated with obliteration. The new grading system assigned 2, 1, and 0 points to DAVFs in the anterior skull base or middle fossa, DAVFs with CVR or DAVFs in the superior sagittal sinus or tentorium, and DAVFs without these factors, respectively. Using the total points, patients were stratified into the highest (0 points), intermediate (1 point), or lowest (≥2 points) obliteration rate groups that exhibited 4-year obliteration rates of 94.4%, 71.3%, and 60.4%, respectively (P<0.01).CONCLUSIONS:SRS-based therapy achieved DAVF obliteration in more than three-quarters of the patients at 4 years of age. Our grading system can stratify the obliteration rate and may guide physicians in treatment selection.

Objective: We have reported a case of a patient with hemifacial spasm (HFS) and nervus intermedius neuralgia associated with hyperfunction and hypofunction of the nervus intermedius. Clinical presentation: A 60-year-old man presented with a 6.5-year history of pain around the left eyelid and dry mouth. Three years prior, he noticed paroxysmal twitching of the left eyelid, and 1 year later, the spasm had extended to the entire left face. Simultaneously, he experienced left nose and left ear pain that was not aggravated by chewing, talking, or washing the face as well as nasal discharge. One year later, the facial spasms had aggregated. The patient was referred to our hospital for microvascular decompression (MVD) for HFS. Examination revealed normal findings, except severe HFS associated with slight left facial weakness. Three-dimensional magnetic resonance imaging (3D-MRI) showed neurovascular contact around the root exit zone (REZ) of the vestibulocochlear nerves by the posterior inferior cerebellar artery (PICA). MVD was performed via the left retrosigmoid approach, with interposition using a sponge made of urethane foam between the REZ of the facial nerve and PICA. The left nose and ear pain, dry eye, dry mouth, and nasal discharge were completely relieved 1 week after MVD. The HFS in the left face gradually improved and completely resolved 6 months after surgery. Conclusion: Although the association between HFS and nervus intermedius neuralgia has been previously reported, this is the first report of a case associated with symptoms of hyperfunction and hypofunction of the nervus intermedius successfully treated by MVD of the REZ of the seventh and eighth nerves.

An 82-year-old female had suffered right facial pain since 37 years of her age. The trigeminal neuralgia (TN) was controlled by carbamazepine and peripheral nerve block. The local block was effective for two to three years once performed, and as it became less effective, the patient took carbamazepine. Four months before gamma knife radiosurgery (GKRS), TN worsened. Analysis of her blood sample revealed autoimmune hemolytic anemia. It was suspected to be related to carbamazepine, and the patient stopped taking carbamazepine. The patient suffered pharyngeal pain and had difficulty swallowing for two months before GKRS. Tube feeding was started one month before GKRS. The patient was considered in pain due to TN and glossopharyngeal neuralgia (GPN). We performed GKRS continuously on the right cisternal portion of the trigeminal nerve at a maximum radiosurgical dose of 85 Gy for TN, and on the right cisternal portion of the glossopharyngeal nerve at a maximum dose of 80 Gy for GPN on the same day. The facial pain improved the day after GKRS. Seven days after treatment, the patient could swallow without pharyngeal pain, and the gastric tube was removed. Thirteen months after GKRS, the TN re-occurred but was controlled by carbamazepine 400 mg per day. GPN did not recur at that time. Simultaneous GKRS for concurrent TN and GPN is a less invasive and useful treatment option for non-candidates for surgical interventions.

OBJECTIVE:The present study evaluated outcomes after preplanned partial surgical removal of a large vestibular schwannoma (VS) followed by low-dose Gamma Knife surgery (GKS).METHODS:Between January 2000 and May 2015, 47 patients with a unilateral VS (median maximum diameter 32 mm) underwent preplanned partial tumor removal at our clinic. GKS for a residual lesion was done within a median time interval of 3 months. The median prescription dose was 12 Gy. The median length of subsequent follow-up was 74 months.RESULTS:The actuarial tumor growth control rates without a need for additional management at 3, 5, and 15 years after GKS were 92%, 86%, and 86%, respectively. At the time of the last follow-up, the function of the ipsilateral facial nerve corresponded to House-Brackmann grade I in 92% of patients. Significant improvement of ipsilateral hearing was noted in two patients after partial tumor removal and in one after GKS. Among 16 patients who presented with ipsilateral serviceable hearing, it was preserved immediately after surgery in 81% of cases and at the time of the last follow-up in 44%. Salvage surgical treatment was required in 9% of patients.CONCLUSION:Preplanned partial surgical removal followed by low-dose GKS provides a high level of functional preservation in patients with a large VS.

To evaluate the efficacy of gamma knife radiosurgery (GKS) for brain metastases (BMs) from small-cell lung cancer after whole-brain radiotherapy (WBRT). We retrospectively analyzed the usefulness and safety of GKS in 163 patients from 15 institutions with 1–10 active BMs after WBRT. The usefulness and safety of GKS were evaluated using statistical methods. The median age was 66 years, and 79.1% of patients were men. The median number and largest diameter of BM were 2.0 and 1.4 cm, respectively. WBRT was administered prophylactically in 46.6% of patients. The median overall survival (OS) was 9.3 months, and the neurologic mortality was 20.0%. Crude incidences of local control failure and new lesion appearance were 36.6% and 64.9%, respectively. A BM diameter ≥ 1.0 cm was a significant risk factor for local progression (hazard ratio [HR] 2.556, P = 0.039) and neurologic death (HR 4.940, P = 0.031). Leukoencephalopathy at the final follow-up was more prevalent in the therapeutic WBRT group than in the prophylactic group (P = 0.019). The symptom improvement rate was 61.3%, and neurological function was preserved for a median of 7.6 months. Therapeutic WBRT was not a significant risk factor for OS, neurological death, local control, or functional deterioration (P = 0.273, 0.490, 0.779, and 0.560, respectively). Symptomatic radiation-related adverse effects occurred in 7.4% of patients. GKS can safely preserve neurological function and prevent neurologic death in patients with 1–10 small, active BMs after prophylactic and therapeutic WBRT.

Objective The optimal treatment for a craniopharyngioma has been controversial. Complete resection is ideal, but it has been difficult to obtain total resection in many cases because of intimate proximity to critical structures such as the optic pathway, hypothalamus, and pituitary gland. A growing number of studies have demonstrated the utility of radiosurgery in controlling residual or recurrent craniopharyngioma. However, most of them are small series. The aim of this multi-institutional study was to clarify the efficacy and safety of Gamma Knife (Elekta, Stockholm, Sweden) surgery for patients with a craniopharyngioma. Methods This was a multi-institutional retrospective study by 16 medical centers of the Japan Leksell Gamma Knife Society. Data on patients with craniopharyngiomas treated with Gamma Knife Surgery (GKS) between 1991 and 2013 were obtained from individual institutional review board-approved databases at each center. A total of 242 patients with craniopharyngioma were included in this study. The mean age of the patients was 41 (range, 3 to 86) years. The median follow-up time was 61.4 months (range, 3 to 180 months). The mean radiosurgery target volume was 3.1 ml (range, 0.03-22.3 ml), and the mean marginal dose was 11.4 Gy (range, 8-20.4 Gy). Results Two-hundred twenty patients were alive at the time of the last follow-up visit. The three-, five-, and 10-year overall survival rates after GKS were 95.4%, 92.5%, and 82.0%, respectively. The three-, five-, and 10-year progression-free survival rates after GKS were 73.1%, 62.2%, and 42.6% respectively. The rate of radiation-induced complications was 6.2%. Conclusion GKS is effective for controlling the tumor growth of craniopharyngiomas with an acceptable complication rate.

Intracavernous hemangiopericytoma/solitary fibrous tumor is an extremely rare tumor, with only seven cases reported. We present a case of intracavernous hemangiopericytoma/solitary fibrous tumor and review all cases reported in the literature. A 67-year-old man experienced numbness over the left half of the face. Magnetic resonance imaging revealed a left intracavernous tumor extending into Meckel's cave and the posterior fossa. We performed gamma knife surgery (GKS) which a prescribed dose to the tumor of 12 Gy, but tumor recurred 43 months after GKS. We performed partial tumor resection via a subtemporal interdural approach. The pathological diagnosis was hemangiopericytoma. Postoperatively, we performed second GKS with a prescribed dose of 15 Gy. Diplopia and ptosis improved markedly and the tumor initially reduced in size, but tumor regrowth was seen again 29 months after second GKS. Third GKS was performed with a prescribed dose of 15 Gy. Recurrence was not seen at 18 months after third GKS, but was identified about 2 years after third GKS. We performed fourth GKS with a prescribed dose to the residual tumor of 16 Gy. We report a rare case of intracavernous hemangiopericytoma originating in the cavernous sinus, but distinguishing between hemangiopericytoma and schwannoma is difficult for round, intracavernous tumors showing homogeneous enhancement without flow voids. GKS might be one of the options for residual and recurrent intracavernous hemangiopericytomas.

Purpose: The authors have been treating skull base meningiomas using relatively low-dose gamma knife radiosurgery (GKS, <= 12 Gy) with acceptable tumor growth control and low morbidity. In the present study, volume-staged, low-dose GKS was performed for large skull base meningiomas with a maximum diameter > 4 cm. In this article, a treatment strategy for volume-staged GKS and results for large skull base meningiomas are described. Methods: Data from 27 patients with large skull base meningiomas histopathologically diagnosed as WHO grade I or diagnosed by imaging, who underwent volume-staged GKS between March 1995 and September 2018, were reviewed. Among these patients, 24 were followed-up for > six months. The tumor was located in the parasellar region in nine patients, cavernous sinus region in four, petroclival region in four, petrocavernous sinus region in four, cerebellopontine angle region in two, and in the tent in one. The mean tumor diameters ranged from 31 to 47.8 mm (median 39.4 mm), with tumor volumes between 14.7 and 49.5 cm(3) (median 27.5 cm(3)). Results: The prescribed radiation dose was 8-12 Gy (median 10 Gy). The treatment interval between the first and second GKS was three to nine months (median 5.5 months). The median duration of follow-up after the first GKS was 84 months (range 6-204 months). Tumor volume decreased in nine (37.5%) patients, remained stable in nine (37.5%), and increased (local failure) in six (25%). The actuarial progression-free local control rate was 88% at three years, 78% at five years, 70% at 10 years, and 70% at 15 years. Neurological status improved in three (12.5%) patients, was unchanged in 16 (66.5%), and deteriorated in five (21%). Permanent radiation injury occurred in one (4%) patient. Conclusion: Volume-staged GKS demonstrated the usefulness for large skull meningiomas > 4 cm in diameter, over a long-term follow-up period.

Objective: The prognosis of patients with poor-grade subarachnoid hemorrhage (SAH), especially those with out-of-hospital cardiac arrest (OHCA), is extremely poor. The aim of this study was to assess the prognostic factors and characteristics of patients with SAH with Glasgow Coma Scale (GCS) scores of 3 or 4, including patients with OHCA.

Background: The incidences of metastatic brain tumors from malignant melanomas have increased and survival has been prolonged by novel molecular targeted agents and immunotherapy. However, malignant melanomas are uncommon in Asian populations. Objectives: We retrospectively analyzed treatment efficacy and identified prognostic factors impacting tumor control and survival in Japanese melanoma patients with brain metastases treated with gamma knife radiosurgery (GKRS). Methods: We retrospectively reviewed the medical records of 177 patients with 1,500 tumors who underwent GKRS for brain metastases from malignant melanomas. This study was conducted by the Japanese Leksell Gamma Knife Society (JLGK1501). Results: Six and 12 months after GKRS, the cumulative incidences of local tumor recurrence were 9.2 and 13.8%. Intratumoral hemorrhage (p < 0.0001) and larger tumor volume (p = 0.001) in GKRS were associated with significantly poorer local control outcomes. The use of immune checkpoint inhibitors before GKRS was significantly associated with symptomatic adverse events (p = 0.037). The median overall survival time after the initial GKRS was 7.3 months. Lower Karnofsky performance status scores (p = 0.016), uncontrolled primary cancer (p < 0.0001), and multiple brain metastases (p = 0.014) significantly influenced unfavorable overall survival outcomes. The cumulative incidences of neurological death 6 and 12 months after GKRS were 9.7 and 17.4%, those of neurological deterioration were 14.2 and 19.6%, and those of new tumor appearance were 34.5 and 40.5%. Conclusions: The results of the present multicenter study suggest that GKRS is a relatively effective and safe modality for control of tumor progression in Japanese patients with brain metastases from malignant melanomas.

BACKGROUND:Trigeminal neuralgia is a rare feature of basilar impression, a complication of osteochondrodysplasic disorders. Microvascular decompression is difficult in medically refractory cases. Gamma knife radiosurgery (GKS) is effective for classical trigeminal neuralgia, and we first applied this GKS for a patient suffering from trigeminal neuralgia with basilar impression complicated by osteogenesis imperfecta.CASE DESCRIPTION:An 18-year-old man with type I osteogenesis imperfecta presented with a 2-year history of typical left trigeminal neuralgia affecting the ophthalmic, maxillary, and mandibular nerves. His condition was poorly controlled by carbamazepine and pregabalin. Magnetic resonance imaging confirmed severe basilar impression and an elongated cisternal portion of the left trigeminal nerve. GKS was performed under local anesthesia. The middle part of the cisternal portion of the left trigeminal nerve was chosen as the radiosurgical target, despite the lack of neurovascular compression. The maximum radiosurgical dose was 85 Gy, using a single 4-mm collimator. The patient's trigeminal neuralgia improved by 1 month after GKS, and at 21 months after GKS he remained free of pain and medications.CONCLUSIONS:We report a case of trigeminal neuralgia resulting from severe basilar impression. Conventional microvascular decompression would not have been an appropriate treatment for this patient, so GKS was used. GKS is a simple and effective option even in cases with severe cranial deformity.

下垂体腺腫に対する手術は近年経鼻内視鏡手術が多く行われ, その低侵襲性と良好な術後成績が示されている. しかし, これらの手術に耳鼻咽喉科医が関与している施設は限定され, 術後鼻副鼻腔合併症についての報告は少ない.

Histone H3.3 (H3F3A) mutation in the codon for lysine 27 (K27M) has been found as driver mutations in pediatric glioblastoma and has been suggested to play critical roles in the pathogenesis of thalamic gliomas and diffuse intrinsic pontine gliomas. We report a case of thalamic glioma with H3F3A K27M mutation, which was detected in both the primary tumor diagnosed as diffuse astrocytoma obtained during the first surgery and also in the tumor diagnosed as anaplastic astrocytoma obtained at the second surgery.

The authors retrospectively analyzed cyst formations and expanding haematomas (EHs) that developed after Gamma Knife surgery (GKS) for arteriovenous malformations (AVMs), and evaluated the treatment results of these lesions. Cyst formations and/or EHs which developed after GKS for AVMs were identified in 20 patients (5.0%) out of 404 patients who underwent this procedure. There were nine patients with cyst formations, two with EHs and nine with cyst formations with EHs. These lesions developed between 36 and 192months (median 99months) after GKS. The median nidus volume was 4.7ml (range, 1.8-14.2ml) and the median prescribed margin dose was 20Gy (range, 15-23Gy). The multivariate analysis showed no correlation between the appearance of cyst formations and/or EHs and the patients' age, sex, nidus volume, margin dose, repeated GKS, nidus obliteration, pre-GKS embolization and prior hemorrhage. Surgical treatment was required in nine patients. Eight patients had total removal of the angiomatous lesions (EHs or nodular lesions that were detected as enhancement part on MRI) via a craniotomy and one had a cyst aspiration. There was no recurrence of the lesions in all the patients that underwent a craniotomy. In the patient treated with a cyst aspiration, regrowth of the cyst formation occurred. Surgical treatment should be considered for symptomatic lesions and we recommend total removal of the angiomatous lesions to achieve a complete cure.

OBJECTIVE In 1999, the World Health Organization categorized large cell neuroendocrine carcinoma (LCNEC) of the lung as a variant of large cell carcinoma, and LCNEC now accounts for 3% of all lung cancers. Although LCNEC is categorized among the non-small cell lung cancers, its biological behavior has recently been suggested to be very similar to that of a small cell pulmonary malignancy. The clinical outcome for patients with LCNEC is generally poor, and the optimal treatment for this malignancy has not yet been established. Little information is available regarding management of LCNEC patients with brain metastases (METs). This study aimed to evaluate the efficacy of Gamma Knife radiosurgery (GKRS) for patients with brain METs from LCNEC. METHODS The Japanese Leksell Gamma Knife Society planned this retrospective study in which 21 Gamma Knife centers in Japan participated. Data from 101 patients were reviewed for this study. Most of the patients with LCNEC were men (80%), and the mean age was 67 years (range 39-84 years). Primary lung tumors were reported as well controlled in one-third of the patients. More than half of the patients had extracranial METs. Brain metastasis and lung cancer had been detected simultaneously in 25% of the patients. Before GKRS, brain METs had manifested with neurological symptoms in 37 patients. Additionally, prior to GKRS, resection was performed in 17 patients and radiation therapy in 10. A small cell lung carcinoma-based chemotherapy regimen was chosen for 48 patients. The median lesion number was 3 (range 1-33). The median cumulative tumor volume was 3.5 cm3, and the median radiation dose was 20.0 Gy. For statistical analysis, the standard Kaplan-Meier method was used to determine post-GKRS survival. Competing risk analysis was applied to estimate GKRS cumulative incidences of maintenance of neurological function and death, local recurrence, appearance of new lesions, and complications. RESULTS The overall median survival time (MST) was 9.6 months. MSTs for patients classified according to the modified recursive partitioning analysis (RPA) system were 25.7, 11.0, and 5.9 months for Class 1+2a (20 patients), Class 2b (28), and Class 3 (46), respectively. At 12 months after GKRS, neurological death-free and deterioration-free survival rates were 93% and 87%, respectively. Follow-up imaging studies were available in 78 patients. The tumor control rate was 86% at 12 months after GKRS. CONCLUSIONS The present study suggests that GKRS is an effective treatment for LCNEC patients with brain METs, particularly in terms of maintaining neurological status.