Comparison between retrosigmoid and translabyrinthine approaches for large vestibular schwannoma: focus on cerebellar injury and morbidities.

This study aimed to compare the surgical outcomes and morbidities of retrosigmoid and translabyrinthine approaches for large vestibular schwannoma (VS), with a focus on cerebellar injury and morbidities. Eighty-six consecutive patients with large VS, with a maximal extrameatal diameter > 3.0 cm, were reviewed between August 2010 and September 2018. The surgical outcomes, operating time, volume change of perioperative cerebellar edema, and inpatient rehabilitation related to cerebellar morbidities were compared between the two approaches. In total, 53 and 33 patients underwent the retrosigmoid and translabyrinthine approaches, respectively. The median follow-up time was 34.5 months. Surgical outcomes, including the extent of resection, tumor recurrence, and facial nerve preservation, showed no significant differences between the two groups. Patients who underwent the retrosigmoid approach showed a marginal trend for postoperative lower cranial nerve (LCN) dysfunction (P = 0.068). Although the approaching procedure time was longer in the translabyrinthine group, the tumor resection time was significantly longer in the retrosigmoid group (P = 0.001). The median change in the volume of the perioperative cerebellar edema was significantly larger in the retrosigmoid group (P < 0.001) and significantly related to the retrosigmoid approach, solid VS, and tumor resection time. Most cerebellar and LCN deficits were transient; however, the patients in the retrosigmoid group underwent inpatient rehabilitation more than those in the translabyrinthine group (P = 0.018). Both surgical approaches show equivalent surgical outcomes. Notably, the translabyrinthine approach for large VS has advantages in that it reduces cerebellar injury and related morbidities.

Stereotactic radiosurgery for orbital cavernous venous malformation: a single center's experience for 15 years.

BACKGROUND: Stereotactic radiosurgery such as Gamma Knife radiosurgery (GKRS) has been shown to have a good treatment effect for orbital cavernous venous malformation (CVM). However, radiation-induced retinopathy or optic neuropathy is a vision-threatening complication of orbital irradiation. Predicting the post-treatment visual outcome is critical. METHODS: Clinical and radiological outcomes were investigated in 30 patients who underwent GKRS for orbital CVM between July 2005 and February 2020. Measurement of peripapillary retinal nerve fiber layer (pRNFL) thickness using optical coherence tomography (OCT) was obtained in 14 patients. RESULTS: The median clinical and radiological follow-up periods were 46.6 months (range, 15.9-105.8) and 27.5 months (range, 15.4-105.8), respectively. Twenty-eight patients underwent multisession (4 fractions) GKRS. The median cumulative marginal dose was 20 Gy (range, 16-24). Two patients underwent single-session GKRS. Marginal doses were 15 Gy and 10.5 Gy in each patient. The volume of CVM decreased in 29 (97%) patients. Visual acuity was improved in 6 (20%) patients and was stable in 22 (73%) patients. Visual field defect and exophthalmos were improved in all patients. Serial investigation of OCT showed no statistically significant difference in pRNFL thickness after GKRS. Patients with normal average pRNFL thickness showed better visual recovery than patients with thin average pRNFL thickness. CONCLUSIONS: GKRS is an effective and safe treatment option for orbital CVM. The pRNFL thickness before GKRS can be a prognostic indicator for visual recovery in orbital CVM after GKRS.

Gamma Knife Radiosurgery as a Primary Treatment for Nonfunctioning Pituitary Adenoma Invading the Cavernous Sinus.

OBJECTIVES: Surgical resection of nonfunctioning pituitary adenoma (NFPA) invading the cavernous sinus (CS) remains a challenging and significant factor associated with incomplete resection. The residual tumor in CS is usually treated with adjuvant stereotactic radiosurgery (SRS), but there is little information concerning SRS as an initial treatment for CS-invading NFPA. In this study, we investigated the tumor control rate and clinical outcomes of the patients who received primary gamma knife radiosurgery (GKRS) for CS-invading NFPA. METHODS: This was a single-institute retrospective analysis of 11 patients. CS invasion of tumor was categorized using the modified Knosp grading system. The median tumor volume and maximal diameter were 1.6 cm3 (range 0.4-6.5) and 17.2 mm (range 11.6-23.3), respectively. The median clinical follow-up period was 48.5 months (range 16.4-177.8). The median prescription dose at tumor margin was 15 Gy (range 11-25) and median prescription isodose was 50% (range 45-50). The maximum radiation dose to optic chiasm and optic nerve were 7.2 Gy (range 3.4-9.2) and 7.5 Gy (range 4.5-11.5), respectively. RESULTS: Tumor control was achieved in all patients. The median tumor volume and maximal diameter at last follow-up were 0.4 cm3 (range 0.1-2.3) and 11.4 mm (range 4.7-19.5), respectively. The median volume reduction rate was 52% (range 33-88). Six patients showed downgrading of modified Knosp grade after GKRS. No patients developed GKRS-related complications such as hypopituitarism or visual disturbance. CONCLUSIONS: SRS may be an alternative primary treatment option for CS-invading NFPA if there is no urgent and absolute indication for surgery such as optic apparatus compression.

Fractionated stereotactic radiosurgery for malignant gliomas: comparison with single session stereotactic radiosurgery.

PURPOSE: Stereotactic radiosurgery (SRS) is feasible for malignant glioma; however, delivering the optimal radiation dose with sufficient large-volume coverage is a major concern. We aimed to investigate the clinical efficacy and safety of fractionated SRS (fSRS) versus single-session SRS (sSRS) for malignant gliomas. METHODS: We retrospectively reviewed 58 malignant glioma patients who underwent gamma knife SRS from January 2015 to December 2018. Forty-one underwent sSRS, and 17 underwent fSRS. Median dose for fSRS was 28 Gy (range 24-35 Gy), with a median dose of 6 Gy per fraction (range 5-7 Gy). Patients received 4 or 5 fractions on consecutive days. Median dose for sSRS was 18 Gy (range 11-25 Gy), with a median isodose of 50% (range 50-65%). Mean target volumes were 5.9 and 19.3 cc for sSRS and fSRS, respectively (p < 0.001, two-sided t test). RESULTS: After SRS, median progression-free survival (PFS) was 4.5 and 4.6 months (p = 0.58), and median overall survival (OS) was 12.7 and 12.6 months for sSRS and fSRS (p = 0.41), respectively (log-rank test). The incidence of clinically significant radiation necrosis was 20.5% (8/39) and 18.8% (3/16) for sSRS and fSRS, respectively (p = 1, Fisher's exact test). CONCLUSION: fSRS for malignant glioma conferred local control and survival comparable with conventional sSRS. The radiation necrosis incidence was comparable between groups when a parallel biological effective dose was administered to the larger target volumes in the fSRS group. fSRS can be a better alternative to sSRS if re-irradiation is considered for large malignant gliomas.

Outcome of three-fraction gamma knife radiosurgery for brain metastases according to fractionation scheme: preliminary results.

PURPOSE: The optimal interfraction intervals for fractionated radiosurgery has yet to be established. We investigated the outcome of fractionated gamma knife radiosurgery (FGKRS) for large brain metastases (BMs) according to different interfraction intervals. METHODS: Between September 2016 and May 2018, a total of 45 patients who underwent FGKRS for BMs were enrolled in this study. They were divided into two groups (standard fractionation over 3 consecutive days with a 24-h interfraction interval versus prolonged fractionation over 4 or 5 days with an interfraction interval of at least 48-h). BMs with ≥ 2 cm in maximum diameter or ≥ 5 cm3 in volume were included in analysis. RESULTS: Among 52 BMs treated with 3-fraction GKRS, 25 (48.1%) were treated with standard fractionation scheme, and 27 (51.9%) with prolonged fractionation scheme. The median follow-up period was 10.5 months (range 5-25). Local tumor control rates of the standard group were 88.9% at 6 months and 77.8% at 12 months, whereas those of the prolonged group were 100% at 6 and 12 months (p = 0.023, log-rank test). In multivariate analysis, fractionation scheme (hazard ratio [HR] 0.294, 95% CI 0.099-0.873; p = 0.027) and tumor volume (HR 0.200, 95% CI 0.051-0.781; p = 0.021) were revealed as the only significant factors affecting the local tumor control after 3-fraction GKRS. CONCLUSIONS: Our preliminary tumor control results suggest a promising role of 3-fraction GKRS with an interfraction interval of at least 48-h. This fractionation regimen could be an effective and safe treatment option in the management of large BMs.

The influence of histology on the response of brain metastases to gamma knife radiosurgery: a propensity score-matched study.

BACKGROUND: In terms of response to fractionated radiotherapy, metastatic brain tumors of certain origins are considered radioresistant. OBJECTIVE: To determine the influence of "radioresistant" histology on outcomes of brain metastases treated with radiosurgery. METHODS: Between 2001 and 2017, 121 patients with brain metastases from renal cell carcinoma (RCC) and 2151 from non-small cell lung cancer (NSCLC) were reviewed. Eighty-seven pairs were derived using propensity score matching. Local progression-free survival (PFS), progression patterns, distant PFS, and overall survival were investigated. RESULTS: The median follow-up period was 13.7 months (range, 1.6-78.4 months). A total of 536 lesions were treated using gamma knife radiosurgery (GKS), with a median dose of 20 Gy (range, 12-28 Gy). The actuarial local PFS rates in the RCC group were 91% and 89% at 6 and 12 months, respectively, and did not differ from the NSCLC group (97% and 83% at 6 and 12 months, respectively). Continuous progression, without response to GKS, was noted in seven of the eight progressed RCCs. However, six of the seven progressed NSCLCs showed transient shrinkage before progression. The median distant PFS was 9.3 months (95% CI, 6.3-12.2) in the RCC group and 8.0 months (95% CI, 5.5-10.4) in the NSCLC group. The median overall survival was 16.1 months (95% CI, 11.3-20.8) and 14.9 months (95% CI, 11.9-17.8) in RCC and NSCLC groups, respectively. CONCLUSION: Histological differences had no effect on local control in the single high-dose range used for radiosurgery. However, changes in tumor volume during progression varied across tumor histology.

Gamma knife radiosurgery for trigeminal neuralgia secondary to benign lesions.

BACKGROUND: Investigate the clinical outcomes of gamma knife radiosurgery (GKS) in patients with benign intracranial lesions and accompanying trigeminal neuralgia (TN). METHODS: From February 2002 to November 2011, 50 patients (11 males, 39 females) underwent GKS for intracranial lesions accompanied by TN. Pathological diagnoses included meningioma in 30 patients, vestibular schwannoma in 11, trigeminal schwannoma in 7, epidermoid cyst in 1, and arteriovenous malformation in 1. Twenty-two (44%) had a lesion dominantly located in the middle fossa and 26 patients (52%) in the posterior fossa. Twenty-five (50%) patients complained of type I pain, and 18 patients (36%) suffered from type II pain. The other 7 patients (14%) presented with facial pain that could not be determined. Pain was assessed retrospectively by subjective descriptions and with the Barrow Neurological Institute pain intensity score before and after GKS. RESULTS: Tumor control was evaluated with magnetic resonance imaging in 44 (95.7%) of 46 patients over a median follow-up period of 54.8 months (range, 13-142 months). Initial improvement in pain after GKS was observed in 46 (92%) patients. The percentage of patients with improved Barrow Neurological Institute score was 73.5% at 1 year, 70.7% at 2 years, and 76.5% at 3 years. Complete pain relief at the final follow-up was achieved in 18 patients (36%). Pain recurred in 13 patients (28.3%) after initial improvement. Pathological diagnosis, location of the lesion, and type of facial pain did not influence the initial pain response after GKS. Pain recurred more frequently in patients with meningioma than in those with schwannoma (P = .045). Type II pain showed better response to the treatment (P = .006). CONCLUSION: The majority of patients with facial pain secondary to a benign intracranial lesion showed improvement after GKS. However, a substantial proportion of the patients experienced incomplete pain relief and recurrence. GKS needs to be combined with an additional modality or the technique must be modified to achieve complete and durable pain control.

Outcome of gamma knife radiosurgery for metastatic brain tumors derived from non-small cell lung cancer.

The purpose of this study was to analyze outcomes in patients treated with gamma knife radiosurgery (GKS) for brain metastases from non-small cell lung cancer (NSCLC). We retrospectively reviewed the medical records of 817 patients who underwent GKS for brain metastases from NSCLC between January 2002 and December 2012. A total of 1363 GKS procedures were performed for 2970 lesions. The median overall survival time from the initial GKS was 13 months and the salvage treatment-free survival from the first GKS was 6.5 months. Younger age (≤65 years), female sex, better RPA class, higher DS-GPA score, adenocarcinoma, synchronous onset, and lower integrated value of the "numbers and cumulative volume of tumors" were associated with better outcomes. Among the 601 patients with an available follow up image, the pattern of the first progression after initial GKS was the development of new lesions in 356 patients (59.2 %), regrowth of treated lesions in 106 patients (17.6 %), and leptomeningeal seeding (LMS) in 51 patients (8.5 %). Among the deceased, the last MRI performed prior to death was evaluated in 409 patients and showed progression in 263 patients (64.3 %), despite multiple salvage treatments. LMS was identified in 63 patients (15.4 %); a rate much higher than the incidence at first progression. Intracranial tumor burden, defined as the integrated value of the "number of the lesions and cumulative tumor volume", is a new prognostic factor of greater significance than tumor volume or number alone when analyzed as separate factors. Although the cause of death was not progression of brain lesions in the majority of patients, the brain lesions tended to have been persistently progressive in most patients, despite repeated salvage treatment. LMS is an important pattern of treatment failure, in addition to local progression or development of new lesions, particularly in the terminal phase of the disease.

Comparative clinical outcomes of irrigation techniques in burr-hole craniostomy for chronic subdural hemorrhage: a multicenter cohort study.

BACKGROUND: Chronic Subdural Hemorrhage(cSDH) is often treated with surgical blood drainage, but concerns about recurrence and outcomes persist. Surgical techniques, including irrigation, vary. This study compares the outcomes of irrigation in cSDH surgery. MATERIALS AND METHODS: From September 2020 to September 2022, 92 cSDH patients underwent surgery. Two different irrigation methods were used: extensive irrigation (IG) and non-irrigation (NIG). Method of irrigation was selected by each surgeon's preference. Parameters measured included volume of hematoma changes, midline shifting, complications, and basic demographics. Recurrence was defined as symptomatic or hematoma expansion more than double the volume before surgery. Factors predicting recurrence and irrigation method impact were analyzed. RESULTS: Eleven patients were excluded because of bilateral or related to other disease. We analyzed 81 patients (44 NIG, 37 IG). Recurrence occurred in 6 IG cases (16.2%) and 1 NIG case (2.3%). Irrigation method significantly affected recurrence (P = 0.043). Age, gender, medication, medical history, and preoperative measurements had no major impact on recurrence. NIG had unexpected cases of intracerebral hemorrhage. CONCLUSION: Extensive irrigation may increase recurrence in cSDH drainage. Non-irrigation drainage had fewer recurrences, but unexpected complications arose. Careful drainage in non-irrigated cases is crucial.

Lateral Spread Response: Unveiling the Smoking Gun for Cured Hemifacial Spasm.

Hemifacial spasm (HFS) is a rare disorder characterized by involuntary facial muscle contractions. The primary cause is mechanical compression of the facial nerve by nearby structures. Lateral spread response (LSR) is an abnormal muscle response observed during electromyogram (EMG) testing and is associated with HFS. Intraoperative monitoring of LSR is crucial during surgery to confirm successful decompression. Proper anesthesia and electrode positioning are important for accurate LSR monitoring. Stimulation parameters should be carefully adjusted to avoid artifacts. The disappearance of LSR during surgery is associated with short-term outcomes, but its persistence does not necessarily indicate poor long-term outcomes. LSR monitoring has both positive and negative prognostic value, and its predictive ability varies across studies. Early disappearance of LSR can occur before decompression and may indicate better clinical outcomes. Further research is needed to fully understand the implications of LSR monitoring in HFS surgery.

Management of Cerebrospinal Fluid Leakage after Microvascular Decompression Surgery: Clinical Strategy.

(1) Background: Cerebrospinal fluid (CSF) leakage is one of the most common complications of microvascular decompression (MVD) surgery. Before fatal complications, such as intracranial infection, occur, early recognition and prompt treatment are essential. (2) Methods: The clinical data of 475 patients who underwent MVD surgery from September 2020 to March 2023 were retrospectively analyzed. In these patients, if there were any symptoms of CSF leakage, and if CSF leakage was evident, a lumbar drainage catheter was inserted immediately. (3) Results: CSF leakage was suspected in 18 (3.8%) patients. Five of these patients (1.1%) showed signs of CSF leakage during conservative management and subsequently underwent catheter insertion for lumbar drainage. The lumbar drain was removed after an average of 5.2 days, resulting in an average hospitalization of 14.8 days. In all 5 patients, CSF leakage was resolved without reoperation. (4) Conclusions: Our treatment strategy prevented the development of fatal complications. Close observation of the symptoms and postoperative temporal bone computed tomography and audiometry are considered to be good evaluation methods for all patients. If CSF leakage is certain, it is important to perform lumbar drainage immediately.

Recent Advances in Intraoperative Brainstem Auditory Evoked Potential Monitoring during Microvascular Decompression Surgery for Hemifacial Spasm.

Brainstem auditory evoked potential (BAEP) testing during microvascular decompression (MVD) is very important in the treatment of hemifacial spasm (HFS). The reason for this is that the vestibulocochlear nerve is located immediately next to the facial nerve, so the vestibulocochlear nerve may be affected by manipulation during surgery. BAEP testing for detecting vestibulocochlear nerve damage has been further developed for use during surgery. In most HFS patients with normal vestibulocochlear nerves, the degree of vestibulocochlear nerve damage caused by surgery is well-reflected in the BAEP test waveforms. Therefore, real-time testing is the best way to minimize damage to the vestibulocochlear nerve. The purpose of this study was to review the most recently published BAEP test waveforms that were obtained during MVD surgery to determine the relationship between vestibulocochlear nerve damage and BAEP waveforms.

Optimal method for reliable lateral spread response monitoring during microvascular decompression surgery for hemifacial spasm.

In this study, we propose an optimal method for monitoring the key electrophysiological sign, the Lateral Spread Response (LSR), during microvascular decompression (MVD) surgery for hemifacial spasm (HFS). Current monitoring methods and interpretations of LSR remain unclear, leading to potential misinterpretations and undesirable outcomes." We prospectively collected data from patients undergoing MVD for HFS, including basic demographics, clinical characteristics, and surgical outcomes. Stimulation intensity was escalated by 1 mA increments to identify the optimal range for effective LSR. We designated the threshold at which we can observe LSR as THR1 and THR2 for when LSR disappears, with high-intensity stimulation (30 mA) designated as THR30. Subsequently, we compared abnormal muscle responses (AMR) between the optimal range (between THR1 and THR2) and THR30. Additionally, we conducted an analysis to identify and assess factors associated with artifacts and their potential impact on clinical outcomes. As stimulation intensity increases, the onset latency to detect AMR was shortened. The first finding of the study was high intensity stimulation caused artifact that mimic the wave of LSR. Those artifacts were observed even after decompression thus interfere interpretation of disappearance of LSR. Analyzing the factors related to the artifact, we found the AMR detected at onset latency below 9.6 ms would be the lateral spreading artifact (LSA) rather than true LSR. To avoid false positive LSR from LSA, we should stepwise increase stimulation intensity and not to surpass the intensity that cause LSR onset latency below 10 ms.

The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Recommendation Using the Delphi Method (Version 2023.1).

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, the need for appropriate treatment guidelines for patients with brain tumors was indispensable due to the lack and limitations of medical resources. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. METHODS: The KSNO Guideline Working Group was composed of 22 multidisciplinary experts on neuro-oncology in Korea. In order to reach consensus among the experts, the Delphi method was used to build up the final recommendations. RESULTS: All participating experts completed the series of surveys, and the results of final survey were used to draft the current consensus recommendations. Priority levels of surgery and radiotherapy during crises were proposed using appropriate time window-based criteria for management outcome. The highest priority for surgery is assigned to patients who are life-threatening or have a risk of significant impact on a patient's prognosis unless immediate intervention is given within 24-48 hours. As for the radiotherapy, patients who are at risk of compromising their overall survival or neurological status within 4-6 weeks are assigned to the highest priority. Curative-intent chemotherapy has the highest priority, followed by neoadjuvant/adjuvant and palliative chemotherapy during a crisis period. Telemedicine should be actively considered as a management tool for brain tumor patients during the mass infection crises such as the COVID-19 pandemic. CONCLUSION: It is crucial that adequate medical care for patients with brain tumors is maintained and provided, even during times of crisis. This guideline will serve as a valuable resource, assisting in the delivery of treatment to brain tumor patients in the event of any future crisis.

The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Survey About Specific Clinical Scenarios (Version 2023.1).

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, there was a shortage of medical resources and the need for proper treatment guidelines for brain tumor patients became more pressing. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. As part II of the guideline, this consensus survey is to suggest management options in specific clinical scenarios during the crisis period. METHODS: The KSNO Guideline Working Group consisted of 22 multidisciplinary experts on neuro-oncology in Korea. In order to confirm a consensus reached by the experts, opinions on 5 specific clinical scenarios about the management of brain tumor patients during the crisis period were devised and asked. To build-up the consensus process, Delphi method was employed. RESULTS: The summary of the final consensus from each scenario are as follows. For patients with newly diagnosed astrocytoma with isocitrate dehydrogenase (IDH)-mutant and oligodendroglioma with IDH-mutant/1p19q codeleted, observation was preferred for patients with low-risk, World Health Organization (WHO) grade 2, and Karnofsky Performance Scale (KPS) ≥60, while adjuvant radiotherapy alone was preferred for patients with high-risk, WHO grade 2, and KPS ≥60. For newly diagnosed patients with glioblastoma, the most preferred adjuvant treatment strategy after surgery was radiotherapy plus temozolomide except for patients aged ≥70 years with KPS of 60 and unmethylated MGMT promoters. In patients with symptomatic brain metastasis, the preferred treatment differed according to the number of brain metastasis and performance status. For patients with newly diagnosed atypical meningioma, adjuvant radiation was deferred in patients with older age, poor performance status, complete resection, or low mitotic count. CONCLUSION: It is imperative that proper medical care for brain tumor patients be sustained and provided, even during the crisis period. The findings of this consensus survey will be a useful reference in determining appropriate treatment options for brain tumor patients in the specific clinical scenarios covered by the survey during the future crisis.

Prognostic Value of Lateral Spread Response Recorded 1 Month After Microvascular Decompression for the Treatment of Hemifacial Spasm.

BACKGROUND: The predictive value of intraoperative disappearance of the lateral spread response (LSR) during microvascular decompression surgery for hemifacial spasm treatment is unclear. Studies evaluating the clinical implications of the LSR recorded during the postoperative period are also limited. OBJECTIVE: To analyze the LSR 1 month postoperatively and to evaluate its prognostic value until 1 year postsurgery. METHODS: In total, 883 patients who underwent microvascular decompression between 2016 and 2018 were included. LSR was recorded preoperatively, intraoperatively before decompression, intraoperatively after decompression, and 1 month postoperatively. The outcomes were evaluated at 1 week, 1 month, and 1 year postoperatively. RESULTS: The presence of preoperative and intraoperative LSR after decompression did not predict the postoperative outcome at 1 year. In 246 patients (27.9%), the postoperative LSR at 1 month was not identical to that recorded intraoperatively after decompression. Postoperative LSR at 1 month was associated with a worse outcome at 1 month (P < .0001) and 1 year (P = .0002) postoperatively. Patients with residual symptoms and a LSR 1 month postoperatively were more likely to show residual symptoms 1 year postoperatively, with a positive predictive value of 50.7%. CONCLUSION: Unlike the intraoperative LSR, the LSR at 1 month postoperatively showed prognostic value in predicting 1-year postoperative outcomes and was useful for identifying patients with a high risk of unfavorable outcomes. Thus, confirming the presence of postoperative LSR is necessary.

Subthalamic deep brain stimulation in Parkinson's disease with SNCA mutations: Based on the follow-up to 10 years.

BACKGROUNDS: Although the short-term efficacy of bilateral subthalamic deep brain stimulation (DBS) has been reported in a limited number of Parkinson's disease (PD) patients with SNCA mutations, there are no data for long-term outcome. METHODS: This multicenter retrospective study investigated previously reported PD patients with SNCA mutations, implanted with bilateral subthalamic DBS. We compared demographic and clinical data at baseline and last follow-up. Clinical data of motor and nonmotor symptoms and motor fluctuation were collected up to 10 years from DBS surgery. RESULTS: Among four subjects, three had SNCA duplication and one had c.158C.A (p.A53E) mutation. The mean post-implantation follow-up duration was 5.4 ± 3.7 years. All patients with SNCA duplication showed favorable outcome, although one died from breast cancer 1.5 years after DBS. The patient with the missense mutation became wheelchair-bound due to progressed axial, cognitive and psychiatric symptoms after 3.5 years from DBS despite the benefit on motor fluctuation. CONCLUSION: Based on findings in our small cohort, subthalamic DBS could be beneficial for motor fluctuation in PD patients with SNCA mutations, especially those with SNCA duplication, and cognitive and psychiatric symptoms are important for the long-term outcome of subthalamic DBS.

Clinical Benefit of Bevacizumab and Irinotecan (BEV+IRI) in Patients With Relapsed/Refractory Glioblastoma (r/rGBM) and its Potential Predictors.

BACKGROUND/AIM: Bevacizumab-containing chemotherapy constitutes an important salvage treatment for recurrent/refractory glioblastoma(r/rGBM). PATIENTS AND METHODS: We retrospectively collected the data of r/rGBM patients treated with the combination of bevacizumab and irinotecan (BEV+IRI) as their salvage treatment from July 2013 and December 2021 in Konkuk Medical Center of Korea. Patients with available results from molecular diagnostic tests were eligible, and markers of interest were examined including the presence of MGMT methylation, IDH1/2 mutation, or 1p/19q co-deletion. Efficacy of BEV+IRI and its potential biomarker was explored. RESULTS: Among 21 patients, 38.1% demonstrated European Cooperative Oncology Group-Performance scale (ECOG-PS) ≥3. The majority (71.4%) received BEV+IRI as their second-line chemotherapies, and the median dose was 5 (range=1-25). Objective response rate (ORR) was 33.3% and disease-control rate (DCR) was 85.7%. Irrespective of objective response, early clinical response was achieved in 14(66.7%) patients. During the median follow-up of 16.4 months for survivors, median progression-free survival (PFS) and overall survival (OS) were 3.6 and 6.8 months, respectively. ECOG PS≥3 and TP53 loss were independent predictors of an unfavorable OS, while prompt clinical improvement could predict favorable OS. Any molecular aberration was associated with OS or PFS in the study. CONCLUSION: Salvage BEV+IRI treatment in r/rGBM conferred comparable clinical benefit. ECOG PS ≥3, TP53 loss, and lack of prompt clinical improvement after the treatment were significantly associated with an unfavorable OS.

Immune Checkpoint Inhibitors for Non-Small-Cell Lung Cancer with Brain Metastasis : The Role of Gamma Knife Radiosurgery.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) are approved for treating non-small-cell lung cancer (NSCLC); however, the safety and efficacy of combined ICI and Gamma Knife radiosurgery (GKS) treatment remain undefined. In this study, we retrospectively analyzed patients treated with ICIs with or without GKS at our institute to manage patients with brain metastases from NSCLC. METHODS: We retrospectively reviewed medical records of patients with brain metastases from NSCLC treated with ICIs between January 2015 and December 2017. Of 134 patients, 77 were assessable for brain responses and categorized into three groups as follows : group A, ICI alone (n=26); group B, ICI with concurrent GKS within 14 days (n=24); and group C, ICI with non-concurrent GKS (n=27). RESULTS: The median follow-up duration after brain metastasis diagnosis was 19.1 months (range, 1-77). At the last follow-up, 53 patients (68.8%) died, 20 were alive, and four were lost to follow-up. The estimated median overall survival (OS) of all patients from the date of brain metastasis diagnosis was 20.0 months (95% confidence interval, 12.5-27.7) (10.0, 22.5, and 42.1 months in groups A, B, and C, respectively). The OS was shorter in group A than in group C (p=0.001). The intracranial disease progression-free survival (p=0.569), local progression-free survival (p=0.457), and complication rates did not significantly differ among the groups. Twelve patients showed leptomeningeal seeding (LMS) during follow-up. The 1-year LMS-free rate in treated with ICI alone group (69.1%) was significantly lower than that in treated with GKS before ICI treatment or within 14 days group (93.2%) (p=0.004). CONCLUSION: GKS with ICI showed no favorable OS outcome in treating brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS. Further understanding of the mechanism, which remains unknown, may help improve the quality of life of patients with brain metastasis.

Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer's disease dementia: a phase I clinical trial.

BACKGROUNDS: Alzheimer's disease is the most common cause of dementia, and currently, there is no disease-modifying treatment. Favorable functional outcomes and reduction of amyloid levels were observed following transplantation of mesenchymal stem cells (MSCs) in animal studies. OBJECTIVES: We conducted a phase I clinical trial in nine patients with mild-to-moderate Alzheimer's disease dementia to evaluate the safety and dose-limiting toxicity of three repeated intracerebroventricular injections of human umbilical cord blood-derived MSCs (hUCB-MSCs). METHODS: We recruited nine mild-to-moderate Alzheimer's disease dementia patients from Samsung Medical Center, Seoul, Republic of Korea. Four weeks prior to MSC administration, the Ommaya reservoir was implanted into the right lateral ventricle of the patients. Three patients received a low dose (1.0 × 107 cells/2 mL), and six patients received a high dose (3.0 × 107 cells/2 mL) of hUCB-MSCs. Three repeated injections of MSCs were performed (4-week intervals) in all nine patients. These patients were followed up to 12 weeks after the first hUCB-MSC injection and an additional 36 months in the extended observation study. RESULTS: After hUCB-MSC injection, the most common adverse event was fever (n = 9) followed by headache (n = 7), nausea (n = 5), and vomiting (n = 4), which all subsided within 36 h. There were three serious adverse events in two participants that were considered to have arisen from the investigational product. Fever in a low dose participant and nausea with vomiting in another low dose participant each required extended hospitalization by a day. There were no dose-limiting toxicities. Five participants completed the 36-month extended observation study, and no further serious adverse events were observed. CONCLUSIONS: Three repeated administrations of hUCB-MSCs into the lateral ventricle via an Ommaya reservoir were feasible, relatively and sufficiently safe, and well-tolerated. Currently, we are undergoing an extended follow-up study for those who participated in a phase IIa trial where upon completion, we hope to gain a deeper understanding of the clinical efficacy of MSC AD therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02054208. Registered on 4 February 2014. ClinicalTrials.gov NCT03172117. Registered on 1 June 2017.