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.

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.

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.

Therapeutic effect of genetically modified human neural stem cells encoding cytosine deaminase on experimental glioma.

The aim of this study was to determine the efficacy of neural stem cell-based suicidal gene therapy in rats bearing human glioma. F3 human neural stem cells (NSCs) were transduced to encode cytosine deaminase (CD) which converts 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU). Intratumoral or intravenous transplantation of F3.CD human NSCs led to marked reduction in tumor burden and significantly prolonged the survival of brain tumor-bearing rats. The systemic administration of 5-FC with direct intratumoral/intravenous transplantation of F3.CD cells had remarkable therapeutic effect in rats with human glioma cells as compared with transplantation of parental F3 cells. There was 74% reduction in tumor volume in rats receiving direct transplantation of F3.CD cells into tumor site, and 67% reduction in tumor volume in rats receiving intravenous injection of F3.CD cells as compared to control animals transplanted with human glioma U373 cells alone. The combination of F3.CD and 5-FC was a highly effective in the glioma rat model. Our observations suggest that genetically engineered NSCs encoding suicide gene CD could provide clinical application of suicide gene therapy for patients with glioma.

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.

Intraoperative facial electromyography and brainstem auditory evoked potential findings in microvascular decompression for hemifacial spasm: correlation with postoperative delayed facial palsy.

BACKGROUND: Delayed facial palsy (DFP) after microvascular decompression (MVD) in patients with hemifacial spasm (HFS) is not uncommon, but the cause remains unknown. OBJECTIVES: To assess whether intraoperative electromyography (EMG) and brainstem auditory evoked potential (BAEP) can predict DFP after MVD. METHODS: Between September 2009 and February 2011 we examined 86 patients, 9 of whom (10.4%) developed DFP after MVD on the same side. All patients underwent MVD and were followed-up for a median period of 13 months (range 6-22). We retrospectively examined intraoperative facial EMG and BAEP findings using our MVD patients' registry. We excluded secondary HFS and immediate postoperative facial palsy after MVD in this study. We assessed the prevalence and clinical characteristics of DFP and compared EMG and BAEP findings between DFP and non-DFP groups. RESULTS: All patients recovered completely, with a mean time to recovery of 37.8 days (range 22-57). There were no significant differences between DFP and non-DFP patients in terms of the amplitude and latency of intraoperative EMG and BAEP. CONCLUSION: The usefulness of intraoperative facial EMG and BAEP is limited and cannot predict DFP after MVD for HFS. We speculate that DFP after MVD is not associated with permanent nerve damage according to the EMG findings.

Patients with idiopathic trigeminal neuralgia have a sharper-than-normal trigeminal-pontine angle and trigeminal nerve atrophy.

BACKGROUND: Trigeminal neuralgia (TN) is primarily diagnosed by symptoms and patient history. Magnetic resonance (MR) imaging can be helpful in visualizing the neurovascular compression of the trigeminal nerve in TN patients, but the current parameters used as diagnostic markers for TN are less than optimal. The aim of this study is to assess whether the angle between the trigeminal nerve and the pons (the trigeminal-pontine angle) on the affected side of patients with idiopathic TN differs from that of the unaffected side and that found in controls without TN. METHODS: A case-control study of 30 clinically diagnosed idiopathic TN patients aged 30 to 79 years and 30 age- and sex-matched controls was conducted. We compared the trigeminal-pontine angle and trigeminal nerve atrophy via fast-imaging employing steady-state acquisition (FIESTA) MR imaging. RESULTS: A sharp trigeminal-pontine angle was observed in 25 patients (25/30) on the affected side. As such, the mean angle of the trigeminal nerve on the affected side (40.17) was significantly smaller than that on the unaffected side (48.91, p = 0.001) and that in the control group (52.02, p < 0.001). CONCLUSIONS: A sharp trigeminal-pontine angle on the affected side was found in idiopathic TN patients by FIESTA imaging. This suggests that a sharp trigeminal-pontine angle increases the chance of neurovascular compression on the medial side of the trigeminal nerve.

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 [...].

The growth of brain tumors can be suppressed by multiple transplantation of mesenchymal stem cells expressing cytosine deaminase.

Suicide genes have recently emerged as an attractive alternative therapy for the treatment of various types of intractable cancers. The efficacy of suicide gene therapy relies on efficient gene delivery to target tissues and the localized concentration of final gene products. Here, we showed a potential ex vivo therapy that used mesenchymal stem cells (MSCs) as cellular vehicles to deliver a bacterial suicide gene, cytosine deaminase (CD) to brain tumors. MSCs were engineered to produce CD enzymes at various levels using different promoters. When co-cultured, CD-expressing MSCs had a bystander, anti-cancer effect on neighboring C6 glioma cells in proportion to the levels of CD enzymes that could convert a nontoxic prodrug, 5-fluorocytosine (5-FC) into cytotoxic 5-fluorouracil (5-FU) in vitro. Consistent with the in vitro results, for early stage brain tumors induced by intracranial inoculation of C6 cells, transplantation of CD-expressing MSCs reduced tumor mass in proportion to 5-FC dosages. However, for later stage, established tumors, a single treatment was insufficient, but only multiple transplantations were able to successfully repress tumor growth. Our findings indicate that the level of total CD enzyme activity is a critical parameter that is likely to affect the clinical efficacy for CD gene therapy. Our results also highlight the potential advantages of autograftable MSCs compared with other types of allogeneic stem cells for the treatment of recurrent glioblastomas through repetitive treatments.

Posttreatment high-grade glioma: usefulness of peak height position with semiquantitative MR perfusion histogram analysis in an entire contrast-enhanced lesion for predicting volume fraction of recurrence.

PURPOSE: To determine whether semiquantitative histogram analysis of the normalized cerebral blood volume (CBV) for an entire contrast material-enhanced lesion could be used to predict the volume fraction of posttreatment high-grade glioma recurrence compared with posttreatment change. MATERIALS AND METHODS: The institutional review board approved this retrospective study. Informed consent was obtained. Thirty-nine patients with pathologically proved predominant tumor recurrence (tumor recurrence group, tumor fraction > or =50% [n = 14]), mixed tumor and posttreatment change (mixed group, tumor fraction > or =20% and <50% [n = 10]), and predominant posttreatment change (treatment change group, tumor fraction <20% [n = 15]) were evaluated. Histogram parameters of normalized CBV-histogram width, peak height position (PHP), and maximum value (MV)-were measured in entire contrast-enhanced lesions and used as discriminative indexes. Ordered logistic regression was used to determine independent factors for predicting the diseases of posttreatment contrast-enhanced lesions. Leave-one-out cross-validation was used to determine diagnostic accuracy. RESULTS: PHP was an independent predictive factor (P = .003) for differentiating contrast-enhanced lesions in patients with posttreatment gliomas. According to receiver operating characteristic curve analyses, PHP provided sensitivity of 90.2% and specificity of 91.1% for differentiating tumor recurrence from mixed and treatment change groups at an optimum threshold of 1.7 by using leave-one-out cross-validation. MV helped distinguish treatment change group from tumor recurrence and mixed groups at an optimum threshold of 2.6 (sensitivity, 96.5%; specificity, 93.1%). CONCLUSION: PHP can be used to predict the volume fraction of posttreatment high-grade glioma recurrence.

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.

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.

Neural induction with neurogenin1 increases the therapeutic effects of mesenchymal stem cells in the ischemic brain.

Mesenchymal stem cells (MSCs) have been shown to ameliorate a variety of neurological dysfunctions. This effect is believed to be mediated by their paracrine functions, since these cells rarely differentiate into neuronal cells. It is of clinical interest whether neural induction of MSCs is beneficial for the replacement therapy of neurological diseases. Here we report that expression of Neurogenin1 (Ngn1), a proneural gene that directs neuronal differentiation of progenitor cells during development, is sufficient to convert the mesodermal cell fate of MSCs into a neuronal one. Ngn1-expressing MSCs expressed neuron-specific proteins, including NeuroD and voltage-gated Ca2+ and Na+ channels that were absent in parental MSCs. Most importantly, transplantation of Ngn1-expressing MSCs in the animal stroke model dramatically improved motor functions compared with the parental MSCs. MSCs with Ngn1 populated the ischemic brain, where they expressed mature neuronal markers, including microtubule associated protein 2, neurofilament 200, and vesicular glutamate transporter 2, and functionally connected to host neurons. MSCs with and without Ngn1 were indistinguishable in reducing the numbers of Iba1+, ED1+ inflammatory cells, and terminal deoxynucleotidyl transferase dUTP nick-end labeling(+) apoptotic cells and in increasing the numbers of proliferating Ki67+ cells. The data indicate that in addition to the intrinsic paracrine functions of MSCs, motor dysfunctions were remarkably improved by MSCs able to transdifferentiate into neuronal cells. Thus, neural induction of MSCs is advantageous for the treatment of neurological dysfunctions.

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.

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.

Blood blister-like aneurysms at nonbranching sites of the internal carotid artery.

OBJECT: The clinical features of blood blister-like aneurysms (BBAs) that arise at nonbranching sites of the internal carotid artery (ICA) differ from those of saccular aneurysms. In this study, the authors attempt to describe optimal treatments for BBAs, which have yet to be clearly established. METHODS: Ten of 483 patients with aneurysmal subarachnoid hemorrhage who had been seen at the authors' institution between March 2001 and June 2005 had intraoperatively confirmed BBAs at nonbranching sites of the ICA. All ten patients were women between the ages of 37 and 64 years (mean age 49.3 years); five had a history of hypertension. The BBAs were localized to the right side of the ICA in seven cases. All patients were successfully treated; clipping was undertaken in six, clipping combined with wrapping in three, and trapping in one. These methods were used in conjunction with various other surgical techniques such as brain relaxation by draining cerebrospinal fluid, anterior clinoidectomy, exposing the cervical ICA, gentle subpial dissection (for aneurysms that adhered to the frontal lobe), complete trapping of the ICA before clipping, and protecting the brain. Clip slippage occurred at the end of dural closing in two cases; the aneurysm was completely obliterated using multiple clips combined with ICA stenosis in one of these cases and ICA trapping with good collateral flow in the other. An excellent clinical outcome was achieved in eight patients, whereas two patients were disabled from massive vasospasm. The authors retrospectively reviewed radiological and surgical data in all cases to determine which treatment methods produced a favorable outcome. CONCLUSIONS: Blood blister-like aneurysms located at nonbranching sites of the ICA are difficult to treat. Preoperative awareness and careful consideration of these lesions during surgery can prevent poor clinical outcomes.