Background: We aimed to evaluate long-term outcomes of gamma knife radiosurgery (GKS) for cerebral cavernous malformations (CCMs). Methods: Among the 233 CCM patients who underwent GKS, 79 adult patients (96 lesions) followed for over 10 years were included and analyzed retrospectively. Annual hemorrhage rate (AHR) was analyzed the entire cohort of 233 patients and the subset of 79 enrolled patients by dividing lesions into overall CCM lesions and brainstem lesions. AHR, neurologic outcome, adverse radiation effect (ARE), and changes of lesions in magnetic resonance imaging (MRI) were compared before and after GKS. Cox-regression analysis was performed to identify risk factors for hemorrhage following GKS. Results: Mean follow-up duration of 79 enrolled patients was 14 years (range, 10–23 years).The AHR of all CCMs for entire cohort at each time point was 17.8% (pre-GKS), 5.9% (≤ 2 years post-GKS), 1.8% (≤ 10 years post-GKS). The AHR of all CCM for 79 enrolled patients was 21.4% (pre-GKS), 3.8% (2 years post-GKS), 1.4% (10 years post-GKS), and 2.3% (> 10 years post-GKS). The AHR of brainstem cavernous malformation (CM) for entire cohort at each time point was 22.4% (pre-GKS), 10.1% (≤ 2 years post-GKS), 3.2% (≤ 10 years post-GKS). The AHR of brainstem CM for 79 enrolled patients was 27.2% (pre-GKS), 5.8% (2 years post-GKS), 3.4% (10 years post-GKS), and 3.5% (> 10 years post-GKS). Out of the 79 enrolled patients, 35 presented with focal neurologic deficits at the initial clinical visit. Among these patients, 74.3% showed recovery at the last follow-up. Symptomatic ARE occurred in five (6.4%) patients. No mortality occurred. Most lesions were decreased in size at the last follow-up MRI. Previous hemorrhage history (hazard ratio [HR], 8.38; 95% confidence interval [CI], 1.07–65.88; P = 0.043), and brainstem location (HR, 3.10; 95% CI, 1.26–7.64; P = 0.014) were significant risk factors for hemorrhage event. Conclusion GKS for CCM showed favorable long-term outcomes. GKS should be considered for CCM, especially when it has a previous hemorrhage history and brainstem location.

Background: Treatment for large (> 10 mL) arteriovenous malformations (AVMs) remains highly challenging. This study evaluated long-term effect of time-staged gamma knife radiosurgery (GKS) for large AVMs. Methods: For patients with large AVMs treated by time-staged GKS over 10 years, timestaged GKS was repeated every three years targeting the entire nidus if total obliteration was not achieved. Obliteration rate and post-GKS complications were assessed based on 10 mL volume interval of AVMs. Prognostic factors for these outcomes were evaluated using Cox regression analysis. Results: Ninety-six patients were analyzed. For AVMs in the 10–20 mL subgroup, a dose ≥ 13.5Gy yielded higher obliteration rate in the first GKS. In the 20–30 mL subgroup, a second GKS significantly boosted obliteration. AVMs > 30 mL did not achieve any obliteration with the first GKS. Among 35 (36.4%) cases lost to follow-up, 7 (7.2%) were lost due to GKS complications. Kaplan-Meier analysis showed that each subgroup needed different time for achieving 50% favorable obliteration outcome rate: 3.5, 6.5, and 8.2 years for 10–20 mL, 20–30 mL, and > 30 mL subgroup, respectively. Total obliteration rate calculated by intention-to-treat method: 73%, 51.7%, 35.7%, respectively, 61.5% overall. Post-GKS hemorrhage and chronic encapsulated expanding hematoma (CEEH) occurred in 13.5% and 8.3% of cases, respectively.Two patients died. Dose and volume were significant prognostic factors for obliteration. Initial AVM volume was a significant prognostic factor of post-GKS hemorrhage and CEEH. Conclusion Time-staged GKS for large AVMs less than 30 mL has highly favorable long-term outcome and a tolerable complication rate.

Objective: Obsessive-compulsive disorder (OCD) is a psychiatric condition that causes significant distress and social costs and often follows a chronic course with frequent relapses. Approximately 20% of patients do not respond to medication or cognitive behavioral therapy; gamma knife surgery (GKS) has been proposed as a treatment option for these patients. However, research on GKS for OCD patients is rare. Methods: In this study, 10 patients with treatment-resistant OCD underwent GKS, and the treatment response and side effects were assessed. The improvement in patients’ obsessive-compulsive symptoms was evaluated using the Yale-Brown Obsessive Compulsive Scale (YBOCS) scores following GKS. Additionally, the characteristics distinguishing the groups with favorable responses to GKS from those with less favorable responses were examined. Results: GKS was well tolerated, and patients demonstrated a statistically significant reduction in YBOCS scores before and after GKS (p=0.016). Patients that responded to GKS exhibited distinct characteristics from those who did not respond. Patients who responded poorly tended to present an earlier age of onset, a longer duration of illness, more frequent hospitalizations, poorer social functioning, and a greater incidence of suicide attempts/thoughts. Conclusion This study not only demonstrated that GKS is a safe and effective treatment method for intractable OCD but also revealed characteristics distinguishing patients who respond well to GKS from those who do not. These results may aid in the selection of patients for future application of GKS.

Background: Since the long-term outcomes of 162 patients who underwent gamma knife radiosurgery (GKS) as an initial or adjuvant treatment for acoustic neuromas (ANs) with unilateral hearing loss were first reported in 1998, there has been no report of a comprehensive analysis of what has changed in GKS practice. Methods: We performed a retrospective study of the long-term outcomes of 106 patients with unilateral sporadic ANs who underwent GKS as an initial treatment. The mean patient age was 50 years, and the mean initial tumor volume was 3.68 cm 3 (range, 0.10–23.30 cm 3 ).The median marginal tumor dose was 12.5 Gy (range, 8.0–15.0 Gy) and the median follow-up duration was 153 months (range, 120–216 months). Results: The tumor volume increased in 11 patients (10.4%), remained stationary in 27 (25.5%), and decreased in 68 patients (64.2%). The actuarial 3, 5, 10, and 15-year tumor control rates were 95.3 ± 2.1%, 94.3 ± 2.2%, 87.7 ± 3.2%, and 86.6 ± 3.3%, respectively.The 10-year actuarial tumor control rate was significantly lower in the patients with tumor volumes of ≥ 8 cm 3 (P = 0.010). The rate of maintaining the same Gardner-Robertson scale grade was 28.6%, and that of serviceable hearing was 46.4%. The rates of newly developed facial and trigeminal neuropathy were 2.8% and 4.7%, respectively. The patients who received marginal doses of less than 12 Gy revealed higher tumor control failure rates (P = 0.129) and newly occurred facial or trigeminal neuropathy rates (P = 0.040 and 0.313, respectively). Conclusion GKS as an initial treatment for ANs could be helpful in terms of tumor control, the preservation of serviceable hearing, and the prevention of cranial neuropathy. It is recommended to perform GKS as soon as possible not only for tumor control in unilateral ANs with hearing loss but also for hearing preservation in those without hearing loss.

Objective: To investigate the long-term clinical outcomes of pallidal deep brain stimulation (GPi-DBS) in patients with pantothenate kinase-associated neurodegeneration (PKAN). Methods: We reviewed the records of patients with genetically confirmed PKAN who received bilateral GPi-DBS for refractory dystonia and were clinically followed up for at least 2 years postoperatively at two centers in Korea. Pre- and postoperative Burke– Fahn–Marsden Dystonia Rating Scale motor subscale (BFMDRS-M) scores, disability subscale (BFMDRS-D) scores, and qualitative clinical information were prospectively collected. Descriptive analysis was performed for BFMDRS-M scores, BFMDRSD scores, and the orofacial, axial, and limb subscores of the BFMDRS-M at 6–12, 24–36, and 60–72 months postoperatively. Results: Five classic-type, four atypical-type, and one unknown-type PKAN cases were identified. The mean preoperative BFMDRS-M score was 92.1 for the classic type and 38.5 for the atypical or unknown type, with a mean BFMDRS follow-up of 50.7 months and a clinical follow-up of 69.0 months. The mean improvements in BFMDRS-M score were 11.3%, 41.3%, and 30.5% at 6–12, 24–36, and 60–72 months, respectively. In four patients with full regular evaluations until 60–72 months, improvements in the orofacial, axial, and limb subscores persisted, but the disability scores worsened from 24–36 months post-operation compared to the baseline, mainly owing to the aggravation of eating and feeding disabilities. Conclusion The benefits of GPi-DBS on dystonia may persist for more than 5 years in PKAN. The effects on patients’ subjective disability may have a shorter duration despite improvements in dystonia owing to the complex manifestations of PKAN.

Background: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

Background: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

BACKGROUND: The infratemporal fossa (ITF) is an anatomical lateral skull base space composed by the zygoma, temporal, and the greater wing of the sphenoid bone. Due to its difficult approach, surgical intervention at the ITF has remained a heavy burden to surgeons. The aim of this article is to review basic skull base approaches and ITF structures and to avoid severe complications based on the accurate surgical knowledge. METHODS: A search of the recent literature using MEDLINE (PubMed), Embase, Cochrane Library, and other online tools was executed using the following keyword combinations: infratemporal fossa, subtemporal fossa, transzygomatic approach, orbitozygomatic approach, transmaxillary approach, facial translocation approach, midface degloving, zygomatico-transmandibular approach, and lateral skull base. Aside from our Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) trial, there have been very few randomized controlled trials. The search data for this review are summarized based on the authors’ diverse clinical experiences. RESULTS: We divided our results based on representative skull base approaches and the anatomy of the ITF. Basic approaches to the ITF include endoscopic endonasal, transzygomatic, orbitozygomatic, zygomatico-transmandibular, transmaxillary, facial translocation, and the midfacial degloving approach. The borders and inner structures of the ITF (with basic lateral skull base dissection schemes) are summarized, and the modified zygomatico-transmandibular approach (ZTMA) is described in detail. CONCLUSIONS: An anatomical basic knowledge would be required for the appropriate management of the ITF pathology for diverse specialized doctors, including maxillofacial, plastic, and vascular surgeons. The ITF approach, in conjunction with the application of microsurgical techniques and improved perioperative care, has permitted significant advances and successful curative outcomes for patients having malignancy in ITF.
Humans ; Pathology ; Perioperative Care ; Plastics ; Skull Base ; Sphenoid Bone ; Surgeons ; Zygoma

PURPOSE: We investigated the effect of chemoradiotherapy with PP2 and temozolomide (TMZ) on malignant glioma cells using clonogenic assays and in vivo brain tumor model. MATERIALS AND METHODS: The effect of PP2 on radiosensitivity of U251 and T98G cells was investigated using clonogenic assays. The expression of E-cadherin, matrix metalloproteinases 2 (MMP2), Ephrin type-A receptor 2 (EphA2), and vascular endothelial growth factor (VEGF) was measured by Western blotting and an accumulation of γH2AX foci 6 hours after radiotherapy was measured after PP2 treatment. The effect of PP2 on migration, invasion, and vasculogenic mimicry formation (VMF) of U251 cells was evaluated. In an orthotopical brain tumor model with U251 cells, PP2 was injected intraperitoneally with or without oral TMZ before, during and after whole brain radiotherapy. Bioluminescence images were taken to visualize in vivo tumors and immunohistochemical staining of VEGF, CD31, EphA2, and hypoxia-inducible factor 1a was performed. RESULTS: PP2 increased radiosensitivity of U251 and T98G cells without decreasing survival of normal human astrocytes. Chemoradiotherapy with PP2 and TMZ resulted in increased accumulation of γH2AX foci. PP2 induced overexpression of E-cadherin and suppression of MMP2, VEGF, and EphA2. PP2 also compromised invasion, migration, and VMF of U251 cells. In brain tumors, chemoradiotherapy with PP2 and TMZ decreased tumor volume best, but not statistically significantly compared with chemoradiotherapy with TMZ. The expression of VEGF and CD31 was suppressed in PP2-treated tumors. CONCLUSION: PP2 enhances radiosensitivity of malignant glioma cells and suppresses invasion and migration of U251 cells. Chemoradiotherapy with PP2 and TMZ resulted in non-significant tumor volume decrease.
Astrocytes ; Blotting, Western ; Brain ; Brain Neoplasms ; Cadherins ; Chemoradiotherapy* ; Glioblastoma ; Glioma* ; Humans ; Matrix Metalloproteinases ; Protein-Tyrosine Kinases* ; Radiation Tolerance ; Radiotherapy ; Tumor Burden ; Tyrosine* ; Vascular Endothelial Growth Factor A

PURPOSE: To compare the depiction of brain metastases on contrast-enhanced images with 7.0 tesla (T) and at 1.5T MRI. MATERIALS AND METHODS: Four consecutive patients with brain metastases were scanned on 7.0T whole-body scanner and 1.5T MRI. A 3D T1-weighted gradient echo sequence (3D T1-GRE) at 1.5T (voxel size = 0.9 x 0.9 x 1.5 mm3 after double-dose, gadoterate meglumine, Gd-DOTA) was compared to a 7.0T 3D T1-GRE sequence (voxel size = 0.4 x 0.4 x 0.8 mm3, single-dose Gd-DOTA) in four patients after a 5 minute delay. The number of contrast-enhancing metastases in MPRAGE images was compared in each patient by two radiologists in consensus. We measured contrast ratio of enhancing brain metastases and white matter in 1.5T and 7.0T. RESULTS: In all four patients 7.0T 3D T1-GRE images after single-dose Gd-DOTA and 1.5T after double-dose Gd-DOTA depicted 11 brain metastases equally. In the quantitative analysis of contrast ratios of enhancing brain metastases and white matter, the 1.5T 3D T1-GRE after double-dose showed an increased contrast ratio compared to 7.0T 3D T1-GRE after single-dose (0.961 +/- 0.571 versus 0.885 +/- 0.494; n = 11 metastases). But this difference was not statistically significant (P = 0.711). CONCLUSION: Our preliminary results indicate that 7.0T single-dose Gd-enhanced images were not different to 1.5T double-dose Gd-enhanced images for the detection of brain metastases.
Brain* ; Consensus ; Humans ; Magnetic Resonance Imaging* ; Meglumine ; Neoplasm Metastasis*