BACKGROUND:This study aimed to evaluate the differences in common types of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) with brain metastasis (BM) treated using linear accelerator-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT). METHODS:Between January 2011-December 2023, among 294 consecutive patients with BM from NSCLC, 84 patients with EGFR-mutated NSCLC were enrolled in this study. RESULTS:The median follow-up time after SRS/fSRT was 20.1 months (range: 0.6-109.7 months), while the median overall survival (mOS) after SRS/fSRT was 25.1 months (95% confidence interval [CI]: 18.4-33.5 months). The mOS after initial treatment for NSCLC was 56.2 months (95% CI: 41.7-77.0 months). The mOS after SRS/fSRT in 34 patients with exon 19 deletions and 45 patients with exon 21 mutations with L858R was 20.4 months (95% CI: 13.6-55.9 months) and 28.5 months (95% CI: 16.2-33.5). The two groups showed no difference in the mOS. In univariate analyses using the Cox proportional hazards model, no prognostic factors associated with prolonged survival were identified except for good pretreatment Karnofsky Performance Status score and no prior tyrosine kinase inhibitor use before SRS/fSRT in EGFR-mutated NSCLC. There was no difference in both distant failure and local control in the two groups. CONCLUSION:The difference in survival between EGFR subtypes (exon 21 L858R mutations vs. exon 19 deletion) was not observed after SRS/fSRT in NSCLC.

IntroductionThis study aimed to evaluate the efficacy and safety of adjunctive intravenous (IV) tissue plasminogen activator (tPA) administration following successful mechanical thrombectomy in patients with acute ischemic stroke caused by large vessel occlusion (LVO).MethodsThis single-center retrospective study included patients with anterior circulation LVO who achieved successful recanalization (Thrombolysis in Cerebral Infarction score ≥2b) after endovascular thrombectomy (EVT) between January 2021 and December 2024. Beginning in December 2022, 25% of the standard IV tPA dose (0.6 mg/kg) was administered immediately after successful recanalization (post-IV tPA group), in addition to the standard pre-EVT 75% dose. Parenchymal blood volume (PBV) ratios were assessed using flat-panel detector computed tomography before and after EVT. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Safety outcomes were symptomatic intracranial hemorrhage (sICH), any intracranial hemorrhage (ICH), and 90-day mortality.ResultsFifty-five patients met inclusion criteria (post-IV tPA, n = 21; standard care, n = 34). The post-IV tPA group showed significantly higher post-EVT PBV ratios (1.45 vs. 1.20, p = 0.03) and greater ΔPBV (2.45 vs. 1.81, p = 0.011). Good functional outcomes (mRS 0–2 at 90 days) were more frequent in the post-IV tPA group (61.9% vs. 29.4%, p = 0.025). No significant differences were seen in overall ICH (14.3% vs. 14.7%, p = 1.00), sICH (9.5% vs. 8.8%, p = 1.00), or 90-day mortality (0% vs. 9%, p = 0.54). Patients who exhibited lesion growth on diffusion-weighted imaging showed significantly lower post-EVT PBV and ΔPBV ratios (p = 0.002 and 0.0134, respectively). In subgroup analysis, longer onset-to-recanalization time was associated with hemorrhagic events in the post-IV tPA group (307 min vs. 226 min, p = 0.04).ConclusionAdjunctive IV tPA administration following successful EVT may improve microvascular reperfusion and functional outcomes without increasing hemorrhagic complications, although careful patient selection is warranted. Due to study limitations, results are hypothesis-generating and require further validation in future prospective randomized trials.

Objective Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) is a major cause of delayed cerebral ischemia (DCI) and poor functional outcomes. Although clazosentan, a selective endothelin A receptor antagonist, suppresses cerebral vasospasm, concerns remain regarding fluid retention–related complications. The efficacy and safety of combination therapy with clazosentan and fasudil hydrochloride under strict fluid management have not been fully established. We retrospectively evaluated the efficacy and safety of this combination therapy. Methods We analyzed patients with aSAH due to ruptured cerebral aneurysms treated at our institution between January 2020 and December 2025. Patients were divided into two groups: a 30-month pre-introduction period (pre-clazosentan group) and a 30-month post-introduction period (fasudil + clazosentan group). The pre-clazosentan group received multidrug therapy centered on fasudil hydrochloride, whereas the fasudil + clazosentan group received additional clazosentan (10 mg/h) on top of fasudil hydrochloride. Outcome measures included symptomatic and radiographic cerebral vasospasm, vasospasm-related cerebral infarction, hyponatremia, pleural effusion/pulmonary edema, and modified Rankin Scale (mRS) scores at discharge and at 3 months. Results Compared with the pre-clazosentan group, the fasudil + clazosentan group had significantly lower incidences of symptomatic cerebral vasospasm (3% vs. 19%, p = 0.012), definitive DCI (7% vs. 21%, p = 0.002), angiographic vasospasm, and hyponatremia (9% vs. 26%, p = 0.028). Pulmonary edema occurred more frequently in the fasudil + clazosentan group (35% vs. 13%, p = 0.02); however, clazosentan was discontinued because of severe pulmonary edema in only five patients (7%). Favorable functional outcomes (mRS < 3) were significantly more frequent at discharge (48% vs. 28%, p = 0.041) and at 3 months (55% vs. 39%, p = 0.048). Multivariable logistic regression identified combination therapy as an independent predictor of favorable functional outcomes (odds ratio, 2.597; 95% confidence interval, 1.087–6.211; p = 0.032). Conclusions Our findings suggest that combination therapy with clazosentan and fasudil hydrochloride, when implemented under strict fluid management, may contribute to the suppression of cerebral vasospasm and improved functional outcomes after aSAH.

BACKGROUND AND OBJECTIVES:Spinal epidural teratoma (SET) is a rare spinal tumor, particularly in the pediatric population. Because of its rarity and potential for extensive growth into both intraspinal and extraspinal compartments, surgical strategies are not well-standardized. This study aims to describe a successful 2-stage surgical approach for an extensive infantile SET and review the existing literature. METHODS:A 1-month-old male infant presented with a large SET extending from T4 to L2 and into the posterior mediastinum. A two-stage surgical approach was performed to achieve gross total resection (GTR). The intraspinal tumor was removed using a split-spinous process laminotomy from T7 to L3. This technique used the natural flexibility of the infant's vertebral arches to create an "open-door" access without detaching the paravertebral muscles. The second surgery was performed 1 month later for the remnant tumor located inside the posterior mediastinal space. The intrathoracic tumor was removed using a thoracoscope with only three 5-mm ports and a small incision for specimen extraction. RESULTS:Histopathology confirmed a mature teratoma. Postoperative MRI demonstrated GTR. The patient remained neurologically intact and was discharged without respiratory or surgical complications. At the 16-month follow-up, there was no evidence of recurrence or spinal deformity. A literature review identified only 10 previous cases of pediatric SET, highlighting a male predominance and a high frequency of multilevel extension. Paraparesis was common in most cases, whereas 2 infants presented with dyspnea because of mediastinal compression. Histologically, all except 1 case were mature teratomas, and all cases treated with GTR remained recurrence-free. CONCLUSION:GTR is the gold standard for pediatric SET because of its histologically mature nature. A staged approach with "open-door" split-spinous process laminotomy and thoracoscopic surgery was an effective strategy. Reducing surgical stress is essential in fragile infants with extensive SETs.

BACKGROUND:Trigeminocardiac reflex (TCR) is a vagal reflex produced by trigeminal nerve stimulation that causes bradycardia, hypotension, and, occasionally, cardiac arrest. TCR usually occurs during surgical manipulation of the posterior fossa. In this report, the authors describe an extremely rare case of TCR that developed when a burr hole was drilled on the temporal bone during surgery for an intraventricular meningioma. OBSERVATIONS:The patient was referred to the authors' department after brain imaging revealed a mass lesion in the right trigone of the lateral ventricle. The surgery, which was performed using a transcortical approach via the right temporal lobe, was conducted under general anesthesia with the patient in the supine lateral position. During craniotomy, the patient experienced 17 seconds of cardiac arrest during the drilling of a burr hole in the temporal bone. TCR could not be diagnosed at that time because it occurred during the manipulation of supratentorial craniotomy with a burr hole. The operation was aborted immediately. The second surgery was performed with the patient in the lateral position, and total removal of the tumor was achieved without causing TCR. LESSONS:In this report, the authors describe a rare TCR caused by supratentorial manipulation. https://thejns.org/doi/10.3171/CASE257.

BACKGROUND:We aimed to evaluate the correlation between postoperative seizures (POS) and overall survival in patients with newly diagnosed supratentorial isocitrate dehydrogenase (IDH)-wild glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide. METHODS:This study included 122 patients with newly diagnosed supratentorial IDH-wild glioblastoma who were treated at our hospital between May 2007 and September 2022. Seizures occurring within 7 days after surgery were defined as immediate POS (iPOS). Moreover, seizures from the 8th day after the surgery were defined as delayed POS (dPOS). RESULTS:The median follow-up period and median survival time (MST) from surgery in the entire cohort were 19.3 and 20.4 months, respectively. The rates of iPOS and dPOS in this study were 6.6% (n=8) and 38.5% (n=47), respectively. The MST of patients with iPOS and without iPOS was 27.6 and 20 months, respectively. There was no significant difference between with iPOS and without iPOS. The median time to onset of dPOS was 126 days after surgery. The MST of patients with dPOS and without dPOS was 25.9 and 18.4 months, respectively. Patients with dPOS showed significantly longer survival than those without dPOS (p=0.024). Occurrence of seizures at the initial manifestation of disease was found to be significantly more likely to cause dPOS (p=0.044). CONCLUSION:Among patients with newly diagnosed supratentorial IDH-wild glioblastoma, the prognosis of patients with seizures in the postoperative course was better than that of patients without dPOS.

BackgroundFlow diverter stent (FDS) treatment is an effective option for wide-necked intracranial aneurysms, but adequate neointimal formation and stent apposition are critical to prevent thromboembolic complications. Non-invasive, reliable imaging techniques for assessing neointimal formation remain limited. This study aimed to evaluate the utility of Dyna-3D imaging in assessing neointimal formation after FDS treatment and to compare its performance with conventional 2D-DSA.MethodsThis retrospective study included 61 patients with unruptured intracranial aneurysms treated with FDS between August 2019 and October 2024. Radiological follow-up was performed 3-6 months post-procedure using both 2D-DSA and Dyna-3D imaging. Neointimal coverage was classified into Groups A-C based on the positional relationship between the stent wires and the vessel wall (Group A = wire outside; Group B = partial overlap; Group C = the vessel wall outside). Interobserver agreement, imaging accuracy, and associated clinical factors were analyzed.ResultsComplete neointimal formation (Group A) was identified in 51 cases (83.6%; 95% CI 72.4-90.8) using Dyna-3D and 21 cases (34.4%; 95% CI 23.7-47.0) using 2D-DSA (P < .0001). Dyna-3D demonstrated superior interobserver agreement (Cohen's κ=0.893; 95% CI 0.75-1.00) compared to 2D-DSA (κ=0.459; 95% CI 0.28-0.64) in the evaluation of neointimal formation. Multivariate analysis identified younger age as a significant factor associated with Group A classification across both modalities (2D-DSA: OR 0.93, 95% CI 0.88-0.98, P = .008; Dyna-3D: OR 0.90, 95% CI 0.8-0.97, P = .018). No thromboembolic or hemorrhagic complications were identified during follow-up.ConclusionDyna-3D imaging provides superior visualization of neointimal formation compared to conventional 2D-DSA and enables comprehensive circumferential assessment of stent apposition. These findings suggest that Dyna-3D may offer a useful tool for guiding post-FDS treatment management, including the potential for age-adjusted optimization of antiplatelet therapy duration.

The present study was conducted to evaluate three modalities used to detect extraocular movement during endonasal endoscopic surgery for a skull base tumor to protect cranial nerves from damage; free-run electrooculography (EOG), piezoelectric sensor (PES), and triggered electromyography (t-EMG) monitoring. Twenty patients (8 males, 12 females; average age 61.8 years) treated for a skull base tumor at Nara Medical University from 2018 to 2021 were enrolled. The three modalities were assessed regarding detection of ocular movement during endoscopic endonasal surgery (EES) for a skull base tumor and the results compared. Oculomotor nerve detection by EOG, PES, and t-EMG was noted in 77.8

Background: A direct aspiration, first-pass thrombectomy (ADAPT) has become the standard technique for thrombus removal and involves contact aspiration with a large-bore suction catheter. However, thrombus retrieval can prove difficult in cases where the thrombus volume is large and occlusion extends across branches. Further, access to the thrombus is frequently complicated by the age of the affected population. Methods: We present two cases in which the thrombus was remotely retrieved with the non-attaching remote thrombus-aspiration (NARA) technique to indirectly apply pressure to the thrombus by maintaining negative pressure through a suction catheter while completely blocking antegrade blood flow. Results: Although the aspiration catheter was not guided to the thrombus, aspiration was started under proximal flow control with inflation of the guiding balloon. When aspiration pressure reached the thrombus, the aspirating catheter showed no retrograde blood flow. Both thrombi were retrieved in a single procedure, and blood flow (Thrombolysis in Cerebral Infarction grade 3) was restored in each case. Conclusions: We achieved remote thrombus retrieval using the NARA technique in two cases. Remote thrombus retrieval is feasible even if the tip of the suction catheter cannot reach the thrombus. This technique may be useful in difficult-to-access cases.

Abstract Background. Patients with glioblastoma (GBM) have poor outcomes and novel strategies are needed. Although immunotherapies have been investigated, altering the severe immunosuppressive tumor microenvironment, or so-called “cold tumors”, is difficult. We developed an immunotherapy based on genome-edited natural killer cells (NKCs) with knocking (KO) of checkpoint receptor T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), which would overcome the GBM immunosuppressive tumor microenvironment. Methods. The GBM TIGIT and TIGIT ligand expression patterns were analyzed with GlioVis and The Human Protein Atlas portal. We generated TIGIT KO human primary NKCs using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) with single guide RNA targeting different genome sites on TIGIT coding exons. The genome-edited NKCs underwent comprehensive microarray gene expression analysis. The anti-GBM activity of the genome-edited NKCs was detected with a 2D adherent model and 3D spheroids derived from allogeneic GBM cells. Results. We successfully obtained TIGIT KO NKCs and effective TIGIT expression KO with unchanged immune checkpoint receptor expression. T7 endonuclease I mutation detection assays demonstrated that the ribonucleoproteins disrupted the intended genome sites. Gene expression analysis demonstrated extremely minimal gene expression pattern changes, such as that for the immune responses, in the TIGIT KO NKCs. Targeting TIGIT KO using CRISPR/Cas9 enhanced NKC anti-tumor activity against the 2D adherent cells and 3D GBM spheroids. Conclusions. Here, we established TIGIT KO human primary NKCs, which demonstrated enhanced anti-tumor activity against GBM cell lines and spheroids. Immunotherapy based on CRISPR/Cas9-edited TIGIT KO NKCs could be a promising GBM therapy.

BACKGROUND:Visual field defects are key determinants for surgical intervention in Rathke's cleft cysts (RCCs). While hemianopia and quadrantanopia are typical, atypical visual field defects without cyst enlargement may complicate treatment decision-making. OBSERVATIONS:A 55-year-old woman developed headaches and bilateral paracentral scotoma 1 month after being referred to our hospital for an incidentally detected RCC in the sella, despite no radiographic evidence of cyst growth. Gadolinium-enhanced MRI demonstrated enhancement extending from the cyst wall to the optic chiasm, suggesting inflammatory spread. Endoscopic endonasal surgery to drain the cyst resulted in complete resolution of symptoms. Histological examination confirmed inflammatory cell infiltration of the cyst wall. Follow-up MRI at 2 years postoperatively showed no evidence of cyst recurrence. LESSONS:RCCs can impair vision not only through compression but also, in some cases, via inflammatory involvement of the optic pathways. Even radiographically stable cysts can produce atypical visual field defects, indicative of inflammation. Early recognition of this mechanism is essential for timely surgical intervention and favorable visual outcomes. https://thejns.org/doi/10.3171/CASE25836.

OBJECTIVE:To evaluate the effect of ventricular opening (VO) on recurrence patterns in patients with newly diagnosed glioblastoma (GBM) treated with bis-chloroethyl-nitrosourea (BCNU) wafer implantation. METHODS:This single-center retrospective study included 40 patients with newly diagnosed GBM who received BCNU wafer implantation after tumor resection between March 2013 and February 2022. The patients were categorized into two groups based on whether VO occurred during the GBM resection. While 18 patients had VO, 22 did not have VO. In cases with VO, the ventricular wall defect is closed with gelatin or oxidized regenerated cellulose and fibrin glue before BCNU wafer implantation. Recurrence patterns-classified as local, diffuse, distant, or multifocal-and time to recurrence were compared between patients with and without VO. RESULTS:The median follow-up period for the entire cohort was 32.2 months (interquartile range, 16.7-38 months). Median survival time was comparable between patients with VO and patients without VO (38 vs. 26 months, p=0.53). Recurrence occurred in 31/40 patients (77.5%) in entire cohort. The incidence of recurrence was comparable between patients with VO and patients without VO (14 [77.8%] vs. 17 [77.3%], p=1.0). No significant differences were seen between the two groups in time to recurrence (p=0.59) or recurrence patterns (p=0.35). CONCLUSION:Ventricular opening during surgery with BCNU wafer implantation does not seem to influence the recurrence patterns. Ventricular opening does not induce distant recurrence if appropriate ventricular closure is performed.

Despite standard multimodality treatment, containing maximum safety resection, temozolomide, radiotherapy, and a tumor-treating field, patients with glioblastoma (GBM) present with a dismal prognosis. Natural killer cell (NKC)-based immunotherapy would play a critical role in GBM treatment. We have previously reported highly activated and ex vivo expanded NK cells derived from human peripheral blood, which exhibited anti-tumor effect against GBM cells. Here, we performed preclinical evaluation of the NK cells using an in vivo orthotopic xenograft model, the U87MG cell-derived brain tumor in NOD/Shi-scid, IL-2RɤKO (NOG) mouse. In the orthotopic xenograft model, the retro-orbital venous injection of NK cells prolonged overall survival of the NOG mouse, indirectly indicating the growth-inhibition effect of NK cells. In addition, we comprehensively summarized the differentially expressed genes, especially focusing on the expression of the NKC-activating receptors’ ligands, inhibitory receptors’ ligands, chemokines, and chemokine receptors, between murine brain tumor treated with NKCs and with no agents, by using microarray. Furthermore, we also performed differentially expressed gene analysis between an internal and external brain tumor in the orthotopic xenograft model. Our findings could provide pivotal information for the NK-cell-based immunotherapy for patients with GBM.

Background: Post-stroke epilepsy can reduce patients’ abilities to carry out various activities of daily living. Despite their importance in preventing the onset of post-stroke epilepsy, the prophylactic administration of antiepileptic drugs is controversial due to a lack of high-level clinical research. In this study, we initiated a prospective interventional study of prophylactic antiepileptic drug administration in patients with a subcortical hemorrhage, who are at the highest risk of developing epilepsy after experiencing a stroke. Methods: The study was conducted in a single-center setting and was a single-arm study with no control group; the case entry period started in November 2023 and is due to end in March 2025. Only cases with a subcortical hemorrhage will be included. The treatment regimen used in this study is 2 mg of perampanel per day. Perampanel will be administered for one year, followed by two years of follow-up, for a total study period of three years. The primary endpoint will be the development of epilepsy. Results: Perampanel administration is expected to reduce the incidence of post-stroke epilepsy in comparison to the results of previous reports on the use of alternative treatments. Conclusions: The results of this study will provide new insights into the prevention of post-stroke epilepsy. The relatively small size of this study makes it difficult to provide strong evidence of the efficacy of perampanel, but it may serve as a basis for larger clinical trials.

BACKGROUND:Ventriculoperitoneal (VP) shunt tube migration is recognized as an occasional complication; however, migration into the cardiac system is rare. The authors report a case of VP shunt tube migration into the heart and pulmonary artery and the safe removal of the tube. OBSERVATIONS:The patient had a VP shunt implanted for hydrocephalus after a subarachnoid hemorrhage. The screening chest radiograph taken a few months later showed the migration of the abdominal tube into the heart. Examinations revealed that the abdominal tube had migrated from the left subclavian vein, passed through the superior vena cava, right atrium and ventricle, and looped into the pulmonary artery. The patient had no symptoms; however, there were some risks, such as damage to the valves or fatal arrhythmia. The authors therefore decided to remove the tube. To avoid various intraoperative risks, in particular tube knot formation, the tube was removed under fluoroscopy with a guidewire inserted, which was 0.035 inches for the angiography catheter. The tube was successfully removed without any complications. LESSONS:Knot formation can be one of the fatal complications of shunt tube removal. The authors' technique is an effective method for safe removal. https://thejns.org/doi/10.3171/CASE24127.

OBJECTIVE: This study aimed to evaluate prognostic factors including pre-radiosurgical blood count in elderly patients (EPs) with brain metastasis (BM) who were treated using linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. METHODS: Between January 2011 and November 2021, 101 consecutive EPs with BM were treated by LINAC-based SRS or fSRT using LINAC with a micro-multileaf collimator. EPs were defined as patients aged double dagger 75 years. RESULTS: The tumors originated from the lungs ( n = 90; 89.1%), colon ( n = 2; 2.0%), and others ( n = 9; 8.8%) in these EPs. The median pretreatment Karnofsky Performance Status was 80 (range, 40-100). The median followp time was 10 months (range, 0-76), as was the median survival. The 6-month, 1-year, and 2-year survival in the EP group was 58.3%, 43.2%, and 28.5%, respectively. Freedom from local failure at 6 months and 1 and 2 years was 97%, 95%, and 91.5%, respectively. Freedom from distant failure at 6 months and 1 and 2 years in EPs was 70.6%, 59.4%, and 54.2%, respectively. A high neutrophil/lymphocyte ratio >5.33 was an unfavorable predictor of prognosis for EPs with BMs treated with SRS and fSRT ( P < 0.001). In the EPs, the prognostic factors associated with prolonged survival in the Cox proportional hazards model were being female and a good pretreatment Karnofsky Performance Status. CONCLUSIONS: The findings of our study highlight the efficacy of LINAC-based SRS and fSRT with a micromultileaf collimator in the treatment of EPs with BMs. Neutrophil/lymphocyte ratio can be an important factor in treatment decisions for EPs with BMs.

BACKGROUND: Accurately evaluating plaque characteristics is essential because lesions with lipid -rich plaque put patients at risk of thromboembolic complications from carotid artery stenting. Near -infrared spectroscopy (NIRS) is a diagnostic imaging modality that identifies lipid components from the near -infrared absorption pattern but does not reveal the distribution of calcification. The purpose of this study was to investigate the calcification characteristics of unstable carotid plaques, focusing on relationships between the calcification characteristics revealed by computed tomography angiography and the lipid core distribution derived from NIRS. METHODS: Participants in this retrospective analysis comprised 35 patients (29 men, 6 women; mean age, 76.0 years; range, 52-89 years) who underwent carotid artery stenting in our institute between January 2021 and December 2022. We evaluated the thickness and length of carotid calcifications at the minimal lumen level from preoperative computed tomography angiography and analyzed the relationship with maximum lipid core burden index (max-LCBI) from NIRS. RESULTS: Strong negative linear correlations were observed between the thickness of calcification and maxLCBI at Area (any segment in a target lesion) (r = -0.795, P < 0.001), max-LCBI at minimal lumen area (r = -0.795, P< 0.001) and lipid core burden index ( LCBI ) at lesion (rate of LCBI in entire plaque lesion) (r = -0.788, P < 0.001), respectively. Significant negative linear correlations were observed between distribution of calcification length and max-LCBI at area (r = -0.429, P = 0.01), max-LCBI at minimal lumen area (r = -0.373, P = 0.027), and LCBI at lesion (r = -0.443, P = 0.008). CONCLUSIONS: Thin and ubiquitous carotid calcification was associated with LCBI values derived from NIRS indicative of carotid lipid plaque distribution, implying the possibility of predicting lesion instability.