First Clinical Report on the Treatment of Parkinson's Disease with Fetal Midbrain Precursor Cells.

BACKGROUND: Because human fetal ventral mesencephalic tissue grafts provide promising results in ameliorating Parkinson's disease-implicated motor dysfunctions, human fetal midbrain-derived dopamine neuronal precursor cells are considered good candidates for cell-based therapy for Parkinson's disease in that large quantities of cells can be supplied through a good manufacturing practice-compliant system. OBJECTIVE: We conducted a prospective, phase I/IIa, dose-escalation, open-label "first-in-human" clinical trial with fetal neural precursor cells to assess their safety and therapeutic efficacy in patients with idiopathic Parkinson's disease. METHODS: Fifteen patients were assigned to receive three different doses of cells (4 × 106 , 12 × 106 , and 40 × 106 cells) and completed a 12-month follow-up. The primary outcome was safety, by measuring the presence of grade 3 or higher cells according to National Cancer Institute guidelines and any contaminated cells. Secondary outcomes assessed motor and neurocognitive function, as well as the level of dopamine transporters, by positron emission tomography-computed tomography. RESULTS: Although a pronation-supination and hand/arm movement performance was remarkably enhanced in all three groups (all P < 0.05), the medium- and high-dose-treated groups exhibited significant improvement in Unified Parkinson's Disease Rating Scale Part III only up to 26.16% and 40%, respectively, at 12 months after transplantation without any serious clinical complications or graft-induced dyskinesia in all patients. However, the motor improvements did not correlate with increase in the dopamine transporter on positron emission tomography images. CONCLUSIONS: Our results primarily demonstrate the safety and plausible dose-dependent efficacy of human fetal midbrain-derived dopamine neuronal precursor cells for idiopathic Parkinson's disease. © 2023 International Parkinson and Movement Disorder Society.

Anterior Craniocervical Junctional Neurenteric Cyst.

Intracranial neurenteric cyst at the anterior craniocervical junction is very rare, and its treatment and prognosis have not been established. We report a case of neurenteric cyst at the anterior craniocervical junction and review the relevant literature. A 16-year-old girl presented with a 2-month history of slowly progressive headache. MRI revealed a well-defined intradural extramedullary cyst in the anterior medulla and brain stem with C1 cord compression. We performed gross total resection of the cyst using a far-lateral transcondylar approach. Surgical resection is the treatment of choice for neurenteric cysts at anterior craniocervical junction, the far-lateral transcondylar approach might be the optimal surgical approach.

Correction: Ahn, J.W., et al. CeRNA Network Analysis Representing Characteristics of Different Tumor Environments Based on 1p/19q Codeletion in Oligodendrogliomas. Cancers 2020, 12, 2543.

The authors wish to make the following corrections to this paper [...].

Functional outcome after surgical treatment of cavernous malformation involving ocular motor cranial nerves: A systematic review.

Cavernous malformations (CMs) of cranial nerves (CN) III, IV, and VI are extremely rare, and limited studies have assessed functional outcomes after treatment. This systematic review investigated the clinical features of CMs in ocular motor CNs, including the treatment results, and compared different surgical methods for functional preservation of ocular motor CNs. 'PubMed', 'SCOPUS', 'Web of Science', and 'Google Scholar' databases were searched to identify case reports and studies published between January 1980 and December 2018. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty-seven patients were identified (median age, 46 years; range, 3 months-71 years). CN III was involved in 17 patients (63.0%), CN IV in 8 (29.6%), and CN VI in 2 (7.4%). Treatments included gross total resection (GTR) and nerve transection in 6 patients (22.2%), GTR and nerve continuity preservation in 7 (25.9%), subtotal resection (STR) and nerve continuity preservation in 4 (14.8%), GTR and end-to-end anastomosis in 5 (18.5%), and conservative care in 3 (11.1%), while the treatment method for 2 (7.4%) patients has not been described in the literature. In 22 patients who underwent surgical treatment, functional changes included improvement in 9 patients (40.9%), no change in 10 (45.5%), and worsening symptoms in 3 (13.6%). Functional preservation was achieved in 12 (54.5%) of the 22 patients; the nerve continuity preservation method conferred a significant advantage for functional preservation compared with other surgical methods (p = 0.004). Functional preservation of ocular motor CNs can be achieved by nerve continuity preservation.

CeRNA Network Analysis Representing Characteristics of Different Tumor Environments Based on 1p/19q Codeletion in Oligodendrogliomas.

Oligodendroglioma (OD) is a subtype of glioma occurring in the central nervous system. The 1p/19q codeletion is a prognostic marker of OD with an isocitrate dehydrogenase (IDH) mutation and is associated with a clinically favorable overall survival (OS); however, the exact underlying mechanism remains unclear. Long non-coding RNAs (lncRNAs) have recently been suggested to regulate carcinogenesis and prognosis in cancer patients. Here, we performed in silico analyses using low-grade gliomas from datasets obtained from The Cancer Genome Atlas to investigate the effects of ceRNA with 1p/19q codeletion on ODs. Thus, we selected modules of differentially expressed genes that were closely related to 1p/19q codeletion traits using weighted gene co-expression network analysis and constructed 16 coding RNA-miRNA-lncRNA networks. The ceRNA network participated in ion channel activity, insulin secretion, and collagen network and extracellular matrix (ECM) changes. In conclusion, ceRNAs with a 1p/19q codeletion can create different tumor microenvironments via potassium ion channels and ECM composition changes; furthermore, differences in OS may occur. Moreover, if extrapolated to gliomas, our results can provide insights into the consequences of identical gene expression, indicating the possibility of tracking different biological processes in different subtypes of glioma.

CXCR4-STAT3 Axis Plays a Role in Tumor Cell Infiltration in an Orthotopic Mouse Glioblastoma Model.

Glioblastoma multiforme (GBM) is a fatal malignant tumor that is characterized by diffusive growth of tumor cells into the surrounding brain parenchyma. However, the diffusive nature of GBM and its relationship with the tumor microenvironment (TME) is still unknown. Here, we investigated the interactions of GBM with the surrounding microenvironment in orthotopic xenograft animal models using two human glioma cell lines, U87 and LN229. The GBM cells in our model showed different features on the aspects of cell growth rate during their development, dispersive nature of glioma tumor cells along blood vessels, and invasion into the brain parenchyma. Our results indicated that these differences in the two models are in part due to differences in the expression of CXCR4 and STAT3, both of which play an important role in tumor progression. In addition, the GBM shows considerable accumulation of resident microglia and peripheral macrophages, but polarizes differently into tumor-supporting cells. These results suggest that the intrinsic factors of GBM and their interaction with the TME determine the diffusive nature and probably the responsiveness to non-cancer cells in the TME.

Re-Irradiation and Its Contribution to Good Prognosis in Recurrent Glioblastoma Patients.

BACKGROUND: Radiation therapy, one of the strongest anti-cancer treatments, is already performed to treat primary glioblastoma; however, the effect of repeated radiation therapy for recurrent tumors has not been fully explored. The aim of this study was to determine the efficacy of re-irradiation in treating recurrent glioblastoma. METHODS: The study included 36 patients with recurrent glioblastoma treated with repeated radiation therapy between 2002 and 2016. Stereotactic radiosurgery (SRS) and hypo-fractionated stereotactic radiotherapy (HSRT) were performed in these patients. RESULTS: Fourteen patients received SRS with a median dose of 25 Gy (range, 20-32 Gy) in 1-5 fractions. Twenty-two patients received HSRT with a median dose of 40 Gy (range, 31.5-52 Gy) in 6-20 fractions. There were six treatment-related grade 3 adverse events. Survival analysis showed that re-irradiation significantly prolonged overall survival (OS) and progression-free survival (PFS). The median OS and one-year OS rate after re-irradiation were 17.2 months and 60.4%, respectively. The median PFS and 6-month PFS rate after re-irradiation were 4.4 months and 41.9%, respectively. Of the 36 patients, three survived without any progression in their condition. CONCLUSION: Re-irradiation for recurrent glioblastoma showed favorable outcomes. Radiation dose and fractionation should be carefully considered to minimize radiation necrosis.

Tumor retractor: a simple and novel instrument for brain tumor surgery.

BACKGROUND: It is important to secure a surgical space during brain tumor surgery. One of the commonly used methods is to retract the brain. We hypothesized that the tumor can be retracted and that the normal brain tissue retraction can be minimized during surgery, and thus, the degree of collateral damage caused by brain retraction would be reduced. METHODS: The tumor retractor had a 90°, hard, and sharp tip for fixation of the tumor. The distal part of the retractor has a malleable and thin blade structure. By adjusting the angle of the distal malleable part of the tumor retractor, the operator can make the retracting angle additionally. Retractors with thin blade can be used in a conventional self-retraction system. To pull and hold the tumor constantly, the tumor retractor is held by a self-retraction system. The surgical technique using a tumor retractor is as follows: The first step is to fix the retractor to the tumor. The second step is to pull the retractor in the operator's desired direction by applying force. After the tumor is pulled by adjusting the degree of force and angle, the surgical arm should be held in place to maintain the tumor retracted state. RESULTS: The tumor retractor was used to minimize the brain retraction, pulling the tumor in the opposite direction from the surrounding brain tissue. In clinical cases, we can apply the tumor retractor with good surgical outcomes. CONCLUSIONS: A tumor retractor can be used to pull a tumor and minimize the brain retraction.

Intensive Rehabilitation Therapy Following Brain Tumor Surgery: A Pilot Study of Effectiveness and Long-Term Satisfaction.

OBJECTIVE: To evaluate the effectiveness of intensive rehabilitation to support recovery of neurological function after brain tumor surgery and assess long-term satisfaction. METHODS: This retrospective study included patients with neurological impairment after brain tumor surgery who underwent intensive rehabilitation therapy between December 2013 and May 2017. To assess effectiveness of rehabilitation, functional outcomes (motor, cognition, and activities of daily living [ADL]) were compared between brain tumor group and a control group enrolling stroke patients who received equivalent rehabilitation during the study period. Long-term satisfaction with rehabilitation was evaluated by surveying family caregivers. RESULTS: This study included 21 patients with benign brain tumor, 14 with malignant brain tumor, and 108 with stroke. Significant and similar improvement in motor, cognition, and ADL function were noted in both the brain tumor group and the stroke group. Malignancy status did not influence the extent of functional improvement. According to medical records and surveys, 9 (69.2%) patients with malignant tumor and 2 (11.8%) with benign tumor had expired by the time of the survey. Most family caregivers confirmed that rehabilitation was effective for functional improvement (>60%), expressing overall satisfaction and stating they would recommend such therapy to patients with similar conditions (approximately 70%). CONCLUSION: Intensive rehabilitation may help promote functional improvement following brain tumor surgery regardless of malignancy compared with stroke patients. Family caregivers expressed overall satisfaction with rehabilitation at long-term follow-up. These findings support the provision of intensive rehabilitation therapy for neurologic function recovery following brain tumor surgery.

Upregulation of the NLRC4 inflammasome contributes to poor prognosis in glioma patients.

Inflammation in tumor microenvironments is implicated in the pathogenesis of tumor development. In particular, inflammasomes, which modulate innate immune functions, are linked to tumor growth and anticancer responses. However, the role of the NLRC4 inflammasome in gliomas remains unclear. Here, we investigated whether the upregulation of the NLRC4 inflammasome is associated with the clinical prognosis of gliomas. We analyzed the protein expression and localization of NLRC4 in glioma tissues from 11 patients by immunohistochemistry. We examined the interaction between the expression of NLRC4 and clinical prognosis via a Kaplan-Meier survival analysis. The level of NLRC4 protein was increased in brain tissues, specifically, in astrocytes, from glioma patients. NLRC4 expression was associated with a poor prognosis in glioma patients, and the upregulation of NLRC4 in astrocytomas was associated with poor survival. Furthermore, hierarchical clustering of data from the Cancer Genome Atlas dataset showed that NLRC4 was highly expressed in gliomas relative to that in a normal healthy group. Our results suggest that the upregulation of the NLRC4 inflammasome contributes to a poor prognosis for gliomas and presents a potential therapeutic target and diagnostic marker.

Comparison of dual-time point 18F-FDG PET/CT tumor-to-background ratio, intraoperative 5-aminolevulinic acid fluorescence scale, and Ki-67 index in high-grade glioma.

The aim of this study was to compare preoperative dual-time point F-fluorodeoxyglucose (FDG) uptake pattern with intraoperative 5-aminolevulinic acid (5-ALA) fluorescence in high-grade gliomas. In addition, we assessed for possible associations with a pathologic parameter (Ki-67 index).Thirty-one patients with high-grade glioma (M:F = 19:12, mean age = 60.6 ±â€Š11.2 years) who underwent dual-time point F-FDG positron emission tomography (PET)/computed tomography (CT) scan before surgery were retrospectively enrolled; 5-ALA was applied to the surgical field of all these patients and its fluorescence intensity was evaluated during surgery. Measured F-FDG PET/CT parameters were maximum and peak tumor-to-background ratio (maxTBR and peakTBR) at base (-base) and delayed (-delay) scan. The intensity of 5-ALA fluorescence was graded on a scale of three (grade I as no or mild intensity, grade II as moderate intensity, and grade III as strong intensity).Seven of the patients had WHO grade III brain tumors and 24 had WHO grade IV tumors (mean tumor size = 4.8 ±â€Š1.8 cm). MaxTBR-delay and peakTBR-delay showed significantly higher values than maxTBR-base and peakTBR-base, respectively (all P < .001). Among the F-FDG PET/CT parameters, only maxTBR-delay demonstrated significance according to grade of 5-ALA (P = .030), and maxTBR-delay gradually decreased as the fluorescence intensity increased. Also, maxTBR-delay and peakTBR-delay showed significant positive correlation with Ki-67 index (P = .011 and .009, respectively).Delayed F-FDG uptake on PET/CT images could reflect proliferation in high-grade glioma, and it has a complementary role with 5-ALA fluorescence.

Association of miR-34a, miR-130a, miR-150 and miR-155 polymorphisms with the risk of ischemic stroke.

MicroRNAs (miRNAs or miRs) are small (19-23 nt) non-coding RNA molecules that are endogenous regulators of gene expression. Previous studies have found that some miRNAs are related to the progression of ischemia in the cerebral artery. Furthermore, a recent study found a significant association between miRNA single nucleotide polymorphisms (SNPs) and the risk of ischemic stroke. Therefore, it may be valuable to investigate associations between megakaryocyte formation-related miRNA polymorphisms and the prevalence of ischemic stroke. We thus conducted a case-control study of 1,000 individuals who were screened for 4 miRNA polymorphisms (miR­34a rs6577555C>A, miR-130a rs731384C>T, miR-150 rs73056059G>A and miR­155 rs767649T>A) by PCR-RFLP analysis. The study population comprised 596 patients with ischemic stroke and 404 control subjects without any history of neurological disorders. We observed associations between miRNA polymorphisms and individual stroke subtypes. The miR­150 polymorphisms were significantly associated with ischemic stroke subgroups, such as left anterior descending artery (LAD) disease [GG vs. AA: adjusted odds ratio (AOR), 1.922; 95% confidence interval (CI), 1.003-3.681] and cardioembolism (GG vs. AA: AOR, 2.996; 95% CI, 1.293-6.939). Additionally, Cox proportional analysis indicated that the miR­150GA genotype was associated with survival in patients with ischemic stroke [adjusted hazard ratio (HR), 2.063; 95% CI, 1.142-3.727; P=0.017] and with the LAD subgroup [adjusted HR, 3.021; 95% CI, 1.345-6.785; P=0.008]. Our findings suggest that miR­150 polymorphisms may contribute to the development of ischemic stroke and may potentially act as biomarkers to predict the risk of ischemic stroke. To the best of our knowledge, this is the first study to evaluate the association between miRNA polymorphisms (miR-34aC>A, miR-130aC>T, miR-150G>A and miR-155T>A) and ischemic stroke.

Surgical Treatment of Hemangioblastoma in the Pituitary Stalk: An Extremely Rare Case.

Hemangioblastoma (HBL) in the pituitary stalk is extremely rare. Only 16 such cases have been reported in the past and 5 cases have been treated with surgical procedure. Here, we report surgical case of HBL in the pituitary stalk diagnosed in a 34-year-old woman. The patient underwent a gross-total resection via the modified lateral supra-orbital approach. No recurrence was observed in two years after surgery. To our knowledge, this is the 17th case of HBL in the pituitary stalk and the 6th surgical case. If the tumor is symptomatic and the volume is over 5 cubic centimeters as in our case, we recommend that the surgical resection of the HBL in the pituitary stalk is a more safe and reasonable than radiotherapy.

Intracranial Hemangiopericytomas : A Retrospective Study of 15 Patients with a Special Review of Recurrence.

OBJECTIVE: Although surgical resection is used to treat meningeal hemangiopericytoma (MHPC), there is a high risk of subsequent recurrence. This study investigated factors associated with treatment outcomes and recurrence in patients who had undergone surgical resection of intracranial MHPC. METHODS: Fifteen patients underwent surgical treatments performed by one senior neurosurgeon between 1997 and 2013. Clinical data, radiologic images, surgical outcomes, recurrence, and other relevant characteristics were reviewed and analyzed. RESULTS: Fifteen patients were included in the analysis, 12 (80%) of whom had tumors in the supratentorial region, and 3 (20%) of whom had tumors in the infratentorial region. Complete resection was achieved in all 15 patients, and 3 (20%) patients were administered radiosurgery and conventional radiotherapy after surgery as adjuvant radiotherapy. Three patients developed recurrence, 2 of whom had not received adjuvant radiotherapy. In 1 of the patients who had not received adjuvant radiotherapy, recurrence developed at the original tumor site, 81 months after surgery. The other 2 recurrences occurred at other sites, 78 and 41 months after surgery. The 5- and 10-year overall survival rates were 88.3%, while the 5- and 10-year recurrence-free survival rates were 83% and 52%, respectively. Additionally the mean Ki-67 index differed significantly between patients who did and did not develop recurrence (43% vs. 14%; p=0.001). CONCLUSION: Because of the high risk of MHPC recurrence, MHPC tumors should be completely resected, whenever feasible. However, even when complete resection is achieved, adjuvant radiotherapy might be necessary to prevent recurrence.

Cryptococcal brainstem abscess mimicking brain tumors in an immunocompetent patient.

Usually fungal infections caused by opportunistic and pathogenic fungi had been an important cause of morbidity and mortality among immunocompromised patients. However clinical data and investigations for immunocompetent pathogenic fungal infections had been rare and neglected into clinical studies. Especially Cryptococcal brainstem abscess cases mimicking brain tumors were also much more rare. So we report this unusual case. This 47-year-old man presented with a history of progressively worsening headache and nausea for 1 month and several days of vomituritions before admission. Neurological and laboratory examinations performed demonstrated no abnormal findings. Previously he was healthy and did not have any significant medical illnesses. A CT and MRI scan revealed enhancing 1.8×1.7×2.0 cm mass lesion in the left pons having central necrosis and peripheral edema compressing the fourth ventricle. And also positron emission tomogram scan demonstrated a hot uptake of fluoro-deoxy-glucose on the brainstem lesion without any evidences of systemic metastasis. Gross total mass resection was achieved with lateral suboccipital approach with neuronavigation system. Postoperatively he recovered without any neurological deficits. Pathologic report confirmed Cryptococcus neoformans and he was successively treated with antifungal medications. This is a previously unreported rare case of brainstem Cryptococcal abscess mimicking brain tumors in immunocompetent host without having any apparent typical meningeal symptoms and signs with resultant good neurosurgical recovery.

Clinical experience of glioma surgery using "tailed bullet": overcoming the limitations of conventional neuro-navigation guided surgery.

PURPOSE: Although conventional neuro-navigation is a useful tool for image-guided glioma surgery, there are some limitations, such as brain shift. We introduced our methods using an identifiable marker, a "tailed bullet", to overcome the limitation of conventional neuro-navigation. A tailed bullet is an identifiable tumor location marker that determines the extent of a resection and we have introduced our technique and reviewed the clinical results. MATERIALS AND METHODS: We have developed and used "tailed bullets" for brain tumor surgery. They were inserted into the brain parenchyma or the tumor itself to help identify the margin of tumor. We retrospectively reviewed surgically resected glioma cases using "tailed bullet". Total 110 gliomas included in this study and it contains WHO grade 2, 3, and 4 glioma was 14, 36, and 60 cases, respectively. RESULTS: Gross total resection (GTR) was achieved in 71 patients (64.5%), subtotal resection in 36 patients (32.7%), and partial resection in 3 patients (2.7%). The overall survival (OS) duration of grade 3 and 4 gliomas were 20.9 (range, 1.2-82.4) and 13.6 months (range, 1.4-173.4), respectively. Extent of resection (GTR), younger age, and higher initial Karnofsky Performance Status (KPS) score were related to longer OS for grade-4 gliomas. There was no significant adverse event directly related to the use of tailed bullets. CONCLUSION: Considering the limitations of conventional neuro-navigation methods, the tailed bullets could be helpful during glioma resection. We believe this simple method is an easily accessible technique and overcomes the limitation of the brain shift from the conventional neuro-navigation. Further studies are needed to verify the clinical benefits of using tailed bullets.

Thirteen-year follow-up of parasellar intravascular papillary endothelial hyperplasia successfully treated by surgical excision: case report.

Intracranial intravascular papillary endothelial hyperplasia (IPEH) is very rare, and to our knowledge long-term follow-up results have not been previously published. An 11-year-old boy presented with a 6-month history of progressive visual impairment in the right eye. Magnetic resonance imaging revealed a well-enhanced, large parasellar mass involving the cavernous sinus, right frontal skull base, and ethmoid and sphenoid sinuses. Frontotemporal craniotomy and subtotal resection were performed, and the diagnosis of IPEH was confirmed. The mass increased in size during the following 3 months. A second operation was performed via frontotemporal craniotomy combined with a transsphenoidal approach, and gross-total resection of the tumor was achieved. Adjuvant radiotherapy (5040 cGy) and chemotherapy with interferon were administered. The patient's visual symptoms improved, and there was no recurrence during a 13-year follow-up period. The results of this case indicate that intracranial IPEH can recur with subtotal resection; however, optimal resection with multimodal adjuvant treatment can control the disease for many years, if not permanently.

Endovascular treatment of M2 dissecting aneurysm presenting with subarachnoid haemorrhage.

A 63-year-old woman presented with a ruptured dissecting aneurysm (DA) at the right M2 region of the angular branches. This report describes a rare case of middle cerebral artery DA presenting with a subarachnoid haemorrhage (SAH); the patient was successfully treated with endovascular internal trapping of the DA, without a bypass surgery.

Proteome analysis of human cerebrospinal fluid as a diagnostic biomarker in patients with meningioma.

BACKGROUND: To identify meningioma-specific proteins, cerebrospinal fluid (CSF) from 4 patients with a meningioma and 4 patients with a non-brain tumorous lesion were analyzed. MATERIAL/METHODS: Two-dimensional electrophoresis and electrospray quadrupole time-of-flight tandem mass spectrometry analyses revealed 10 unique spots, containing 11 independent proteins (spot #2 and #4 each contained 2 proteins and spot #3 was not identified) were evident in CSF associated with human meningioma: serum albumin precursor (3 different isoforms), Apolipoprotein E (Apo E), Apolipoprotein J precursor (Apo J), Transthyretin precursor (TTR), Prostaglandin D2 synthase 21 kDa (PTGDS), proapolipoprotein, Chain D hemoglobin Ypsilanti, alpha-1-antitrypsin (AAT), and beta-2-microglobulin precursor (ß2M). RESULTS: The contents of Apo E, Apo J and AAT were increased, while PTGDS, TTR and ß2M were decreased. CONCLUSIONS: The results observed by 2-dimensional electrophoresis were verified by Western blot analysis. The unique proteins may represent possible candidate biomarkers of meningioma.