Bony Surface-Matching Registration of Neuronavigation with Sectioned 3-Dimensional Skull in Prone Position.

BACKGROUND: Neuronavigation has become an essential system for brain tumor resections. It is sometimes difficult to obtain accurate registration of the neuronavigation with the patient in the prone position. Bony surface-matching registration should be more precise than skin surface-matching registration; however, it is difficult to establish bony registration with limited exposed bone. We created a new bony surface-matching method to a sectioned 3-dimensional (3D) virtual skull in a neuronavigation system and registered with a sectioned 3D skull. In this study, the bony surface-matching with sectioned 3D registration is applied to provide precise registration for brain tumor resection in the prone position. METHODS: From May 2023 to April 2024, 17 patients who underwent brain tumor resection in the prone position were enrolled. The navigation system StealthStation S8 (Medtronic, Dublin, Ireland) was used. Bony surface-matching registration with a whole 3D skull in a neuronavigation system was performed. Next, a sectioned 3D skull was made according to the surgical location to compare with the whole 3D skull registration. A phantom model was also used to validate the whole and sectioned 3D skull registration. RESULTS: Whole 3D skull registration was successful for only 2 patients (11.8%). However, sectioned 3D skull registration was successful for 16 patients (94.1%). The examinations with a phantom skull model also showed superiority of sectioned 3D skull registration to whole 3D skull registration. CONCLUSIONS: Sectioned 3D skull registration was superior to whole 3D skull registration. The sectioned 3D skull method could provide accurate registration with limited exposed bone.

Safety of Tailored Transfemoral Carotid Artery Stenting for Symptomatic Elderly Patients: A Single Center Observational Study.

OBJECTIVE: Transfemoral carotid artery stenting (TFCAS) in symptomatic elderly patients (≥70 years old) may have a high periprocedural stroke rate. This study was performed to examine whether tailored TFCAS for symptomatic elderly patients is as safe as that for symptomatic nonelderly patients. METHODS: The subjects were 185 patients with symptomatic internal carotid artery stenosis. Tailored TFCAS including postoperative management was performed based on preoperative examinations of vascular anatomy, plaque imaging, platelet aggregation activity, and cerebral hemodynamic impairment. The major 30-day perioperative stroke rates were examined. RESULTS: The patients included 51 (27.6%) <70 (group Y) and 134 (72.4%) ≥70 (group E) years old. Group E included significantly more cases with an elongated aortic arch, tortuous target lesion, and longer plaques (all P < 0.05). Among all cases, 181 (97.8%) procedures were performed as per preoperative planning. Group E had more frequent use of a proximal embolic protection device and a closed-cell or dual-layer micromesh stent (all P < 0.05). Seven patients (3.8%) had major stroke. Rates of major ischemic stroke (2.0% vs. 3.0%, P = 1.00) and intracranial hemorrhage (2.0% vs. 0.8%, P = 0.48) were low and did not differ significantly between groups Y and E. CONCLUSIONS: Symptomatic elderly patients have several unfavorable factors. However, tailored TFCAS for each patient based on preoperative examinations in symptomatic elderly patients may be as safe as that in symptomatic nonelderly patients.

Association Between Spreading Depolarization and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: Post Hoc Analysis of a Randomized Trial of the Effect of Cilostazol on Delayed Cerebral Ischemia.

BACKGROUND: Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) remains an important problem with a complex pathophysiology. We used data from a single-center randomized trial to assess the effect of a phosphodiesterase inhibitor, cilostazol, in patients with aneurysmal SAH to explore the relationships of DCI with vasospasm, spreading depolarization (SD) and microcirculatory disturbance. METHODS: A post hoc analysis of a single-center, prospective, randomized trial of the effect of cilostazol on DCI and SD after aneurysmal SAH was performed. From all randomized cohorts, patients who underwent both SD monitoring and digital subtraction angiography (DSA) on day 9 ± 2 from onset were included. Cerebral circulation time (CCT), which was divided into proximal CCT and peripheral CCT (as a measure of microcirculatory disturbance), was obtained from DSA. Logistic regression was conducted to determine factors associated with DCI. RESULTS: Complete data were available for 28 of 50 patients. Of the 28 patients, 8 (28.5%) had DCI during the study period. Multivariate analysis indicated a strong association between the number of SDs on the day DSA was performed (i.e., a delayed time point after SAH onset) and DCI (odds ratio 2.064, 95% confidence interval 1.045-4.075, P = 0.037, area under the curve 0.836), whereas the degree of angiographic vasospasm and peripheral CCT were not significant factors for DCI. CONCLUSIONS: There is a strong association between SD and DCI. Our results suggest that SD is an important therapeutic target and a potentially useful biomarker for DCI.

A focal brain-cooling device as an alternative to electrical stimulation for language mapping during awake craniotomy: patient series.

BACKGROUND: Functional mapping in awake craniotomy has the potential risk of electrical stimulation-related seizure. The authors have developed a novel mapping technique using a brain-cooling device. The cooling probe is cylindrical in shape with a thermoelectric cooling plate (10 × 10 mm) at the bottom. A proportional integration and differentiation-controlled system adjusts the temperature accurately (Japan patent no. P5688666). The authors used it in two patients with glioblastoma. Broca's area was identified by electrical stimulation, and then the cooling probe set at 5°C was attempted on it. OBSERVATIONS: Electrocorticogram was suppressed, and the temperature dropped to 8°C in 50 sec. A positive aphasic reaction was reproduced on Broca's area at a latency of 7 sec. A negative reaction appeared on the adjacent cortices despite the temperature decrease. The sensitivity and specificity were 60% and 100%, respectively. No seizures or other adverse events related to the cooling were recognized, and no histological damage to the cooled cortex was observed. LESSONS: The cooling probe suppressed topographical brain function selectively and reversibly. Awake functional mapping based on thermal neuromodulation technology could substitute or compensate for the conventional electrical mapping.

Glioma-initiating cells at tumor edge gain signals from tumor core cells to promote their malignancy.

Intratumor spatial heterogeneity facilitates therapeutic resistance in glioblastoma (GBM). Nonetheless, understanding of GBM heterogeneity is largely limited to the surgically resectable tumor core lesion while the seeds for recurrence reside in the unresectable tumor edge. In this study, stratification of GBM to core and edge demonstrates clinically relevant surgical sequelae. We establish regionally derived models of GBM edge and core that retain their spatial identity in a cell autonomous manner. Upon xenotransplantation, edge-derived cells show a higher capacity for infiltrative growth, while core cells demonstrate core lesions with greater therapy resistance. Investigation of intercellular signaling between these two tumor populations uncovers the paracrine crosstalk from tumor core that promotes malignancy and therapy resistance of edge cells. These phenotypic alterations are initiated by HDAC1 in GBM core cells which subsequently affect edge cells by secreting the soluble form of CD109 protein. Our data reveal the role of intracellular communication between regionally different populations of GBM cells in tumor recurrence.

Targeting glioma-initiating cells via the tyrosine metabolic pathway.

OBJECTIVE: Despite an aggressive multimodal therapeutic regimen, glioblastoma (GBM) continues to portend a grave prognosis, which is driven in part by tumor heterogeneity at both the molecular and cellular levels. Accordingly, herein the authors sought to identify metabolic differences between GBM tumor core cells and edge cells and, in so doing, elucidate novel actionable therapeutic targets centered on tumor metabolism. METHODS: Comprehensive metabolic analyses were performed on 20 high-grade glioma (HGG) tissues and 30 glioma-initiating cell (GIC) sphere culture models. The results of the metabolic analyses were combined with the Ivy GBM data set. Differences in tumor metabolism between GBM tumor tissue derived from within the contrast-enhancing region (i.e., tumor core) and that from the peritumoral brain lesions (i.e., tumor edge) were sought and explored. Such changes were ultimately confirmed at the protein level via immunohistochemistry. RESULTS: Metabolic heterogeneity in both HGG tumor tissues and GBM sphere culture models was identified, and analyses suggested that tyrosine metabolism may serve as a possible therapeutic target in GBM, particularly in the tumor core. Furthermore, activation of the enzyme tyrosine aminotransferase (TAT) within the tyrosine metabolic pathway influenced the noted therapeutic resistance of the GBM core. CONCLUSIONS: Selective inhibition of the tyrosine metabolism pathway may prove highly beneficial as an adjuvant to multimodal GBM therapies.

Impact of Frailty on Medium-Term Outcome in Asymptomatic Patients After Carotid Artery Stenting.

OBJECTIVE: There are few reports on the relationship between carotid artery stenting (CAS) and frailty. In this study, medium-term outcome after CAS in patients with asymptomatic carotid artery stenosis was examined to see the effect of frailty itself. METHODS: A retrospective study was performed in 71 consecutive patients who were treated with CAS for asymptomatic lesions from January 2007 to June 2014. In this study, only patients without neurologic symptoms before treatment were included. Frailty was defined on the basis of the presence of ≥2 of the 5 items on the Cardiovascular Health Study (CHS) Index. The relationship of frailty with a composite endpoint of the incidence of stroke, disease requiring hospital admission, and death for 3 years after CAS was examined. RESULTS: There were 23 cases (average age 73.9 years, median CHS index 3) with frailty and 48 (average age 70.9 years, median CHS index 0) without frailty. There were no differences in comorbidities or CAS perioperative complications between these groups. However, there was a significantly higher incidence of the composite endpoint in patients with frailty (13/23 vs. 4/48, P < 0.001), and in multivariate analysis, frailty was strongly associated with this endpoint (odds ratio 28.24, 95% confidence interval 4.62-172.71). CONCLUSIONS: In CAS conducted for asymptomatic lesions, perioperative complications had no relationship with frailty. However, frailty is likely to be associated with lower activity of daily life in the medium term after CAS, and consideration of underlying diseases is required in patients with frailty.

Cilostazol decreases duration of spreading depolarization and spreading ischemia after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Traditionally, angiographic vasospasm (aVS) has been thought to cause delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, successful treatment of aVS alone does not result in improved neurological outcome. Therefore, there may be other potential causes of poor neurological outcome, including spreading depolarization (SD). A recent study showed beneficial effects of cilostazol on DCI and neurological outcome. The present prospective clinical trial and experimental study focused on effects of cilostazol on SDs. METHODS: Fifty aSAH patients were treated with clip ligation and randomly assigned to a cilostazol (n = 23) or control group (n = 27). Effects of cilostazol on DCI, aVS, and SDs, measured with subdural electrodes, were examined. The effect of cilostazol on SD-induced perfusion deficits (spreading ischemia) was assessed in an aSAH-mimicking model. RESULTS: There was a trend for less DCI in the cilostazol group, but it did not reach our threshold for statistical significance (13.0% vs 40.0%, odds ratio = 0.266, 95% confidence interval [CI] = 0.059-1.192, p = 0.084). However, the total SD-induced depression duration per recording day (22.2 vs 30.2 minutes, ß = -251.905, 95% CI = -488.458 to -15.356, p = 0.043) and the occurrence of isoelectric SDs (0 vs 4 patients, ß = -0.916, 95% CI = -1.746 to -0.085, p = 0.037) were significantly lower in the cilostazol group. In rats, cilostazol significantly shortened SD-induced spreading ischemia compared to vehicle (Student t test, difference = 30.2, 95% CI = 5.3-55.1, p = 0.020). INTERPRETATION: Repair of the neurovascular response to SDs by cilostazol, as demonstrated in the aSAH-mimicking model, may be a promising therapy to control DCI. Ann Neurol 2018;84:873-885.

Activation of the Receptor Tyrosine Kinase AXL Regulates the Immune Microenvironment in Glioblastoma.

Glioblastoma (GBM) is a lethal disease with no effective therapies available. We previously observed upregulation of the TAM (Tyro-3, Axl, and Mer) receptor tyrosine kinase family member AXL in mesenchymal GBM and showed that knockdown of AXL induced apoptosis of mesenchymal, but not proneural, glioma sphere cultures (GSC). In this study, we report that BGB324, a novel small molecule inhibitor of AXL, prolongs the survival of immunocompromised mice bearing GSC-derived mesenchymal GBM-like tumors. We show that protein S (PROS1), a known ligand of other TAM receptors, was secreted by tumor-associated macrophages/microglia and subsequently physically associated with and activated AXL in mesenchymal GSC. PROS1-driven phosphorylation of AXL (pAXL) induced NFκB activation in mesenchymal GSC, which was inhibited by BGB324 treatment. We also found that treatment of GSC-derived mouse GBM tumors with nivolumab, a blocking antibody against the immune checkpoint protein PD-1, increased intratumoral macrophages/microglia and activation of AXL. Combinatorial therapy with nivolumab plus BGB324 effectively prolonged the survival of mice bearing GBM tumors. Clinically, expression of AXL or PROS1 was associated with poor prognosis for patients with GBM. Our results suggest that the PROS1-AXL pathway regulates intrinsic mesenchymal signaling and the extrinsic immune microenvironment, contributing to the growth of aggressive GBM tumors.Significance: These findings suggest that development of combination treatments of AXL and immune checkpoint inhibitors may provide benefit to patients with GBM. Cancer Res; 78(11); 3002-13. ©2018 AACR.

[Effect of Platelet Concentrate Transfusion on Prognosis of Patients with Intracerebral Hemorrhage Treated with Anti-Platelet Agents].

BACKGROUND: A recent randomized control study(the PATCH trial)found no beneficial effect of platelet concentrate(PC)transfusion on the prognosis of patients with intracerebral hemorrhage(ICH)treated with anti-platelet agents(APAs). However, the trial excluded surgical cases. In this study, we examined the effect of PC on ICH, including patients who received surgical treatment. METHOD: A retrospective cohort analysis was performed in 23(11 males, 12 females)of 35 patients diagnosed with ICH and treated with APAs between January 2010 and December 2015 at the Department of Neurosurgery, Yamaguchi University Hospital. Twelve patients were excluded due to the use of anticoagulants or replenishment of coagulation factors. RESULTS: PC transfusion was administered in 12 cases(PC group)but not administered in 11(non-PC group). Conservative therapy at admission was used in 7 and 9 cases in the PC and non-PC groups, respectively, and none of these cases showed hematoma enlargement during conservative therapy. Surgical treatment was performed in 6 and 2 patients in the PC and non-PC groups, respectively, and hematoma enlargement occurred postoperatively in one patient in each group. Outcomes at 3 months after onset showed no significant difference between the groups(mRS 0-3:6 vs. 5 cases, p=0.34). Patients who received PC had no serious adverse events during hospitalization. CONCLUSION: In this study, surgery after PC transfusion was performed without any problems. There was no difference in prognosis between patients who did and did not receive PC. These results suggest that surgery can be performed safely after PC transfusion.

D-Dimer Elevation as a Blood Biomarker for Detection of Structural Disorder in Mild Traumatic Brain Injury.

CT scans are useful in patients with traumatic brain injury (TBI), but the potential risks associated with ionizing radiation are unknown. Further, CT scans are not commonly available in developing countries. In this study, coagulopathy and abnormal fibrinolysis were investigated as blood biomarkers for detection of structural disorder in mild traumatic brain injury (TBI). A total of 88 patients with mild and isolated TBI (Glasgow Coma Scale [GCS] score 14-15) were admitted to Kenwakai Ootemachi Hospital between October 2014 and March 2016. After exclusion of those treated with oral antiplatelet agents and anticoagulants, 73 patients were included in this study. Patients were classified into those with (lesion [+]) and without (lesion [-]) intracranial structural disorder, based on CT scans at admission and follow-up CT or MRI. Age, GCS score, and blood test findings (platelet count, international normalized ratio of prothrombin time [PT-INR], activated partial thromboplastin time [APTT], fibrinogen, fibrin/fibrinogen degradation products [FDP], and D-dimer) on admission were compared between the two groups. The lesion(+) and lesion(-) groups comprised 54 (74%) and 19 patients (26%), respectively. In multivariate logistic regression analysis, D-dimer (3.6 vs. 0.8 µg/mL) was the only significant independent risk factor for structural disorder (p < 0.001). Platelet counts (23.9 vs. 23.5 × 104 /µL), PT-INR (1.05 vs. 1.07), APTT (29.3 vs. 31.7 sec), FDP (12 vs. 2.4 µg/mL), and fibrinogen levels (260.6 vs. 231.3 mg/dL) were not associated with structural disorder. These results show that D-dimer is associated with intracranial structural disorder in mild TBI.

Opening the ventricle during surgery diminishes survival among patients with newly diagnosed glioblastoma treated with carmustine wafers: a multi-center retrospective study.

Carmustine wafers (CW) were approved in Japan for newly diagnosed and recurrent malignant gliomas during 2013. The ventricle is often opened during surgery to achieve maximum resection. While not generally recommended in such situations, CW might be safely achieved by occluding an opened ventricle using gelform or collagen sheets. However, whether CW implantation actually confers a survival benefit for patients who undergo surgery with an open ventricle to treat glioblastoma remains unclear. Clinical, imaging, and survival data were collected in this multicenter retrospective study of 122 consecutive patients with newly diagnosed glioblastoma to determine adverse events and efficacy. Overall, 54 adverse events of all grades developed in 35 (28.6%) patients, with the most common being new seizures (16%). Adverse events did not significantly differ between patients with opened and closed ventricles during surgery. The 10- and 21.7-month, median, progression-free (PFS) and overall survival (OS), respectively did not significantly differ according to resection rates. However, median PFS and OS were significantly longer among patients with closed, than open ventricles (12.8 vs. 7.4 months; p = 0.0039 and 26.9 vs. 18.6 months; p = 0.011, respectively). Implanting CW into the resection cavity during concomitant radiochemotherapy with temozolomide seems to yield better survival rates without increased adverse events. Occlusion of the ventricular opening during surgery might be safe for CW implantation, but less so for treating patients with newly diagnosed glioblastoma.

Continuous Monitoring of Spreading Depolarization and Cerebrovascular Autoregulation after Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is a prominent complication after aneurysmal subarachnoid hemorrhage (aSAH). Although vasospasm of proximal cerebral arteries has been regarded as the main cause of DCI, vasospasm of distal arteries, microthrombosis, impaired autoregulation, cortical spreading depolarization (CSD), and spreading ischemia are thought to be involved in DCI after aSAH. Here, we describe a patient with aSAH in whom CSD and cerebrovascular autoregulation were evaluated using simultaneous electrocorticography and monitoring of the pressure reactivity index (PRx) after surgical clipping of a ruptured posterior communicating artery aneurysm. In this patient, a prolonged duration of CSD and elevation of PRx preceded delayed neurological deficit. Based on this observation, we propose a relationship between these factors and DCI. Assessment of cerebrovascular autoregulation may permit detection of the inverse hemodynamic response to cortical depolarization. Detection of DCI may be achieved through simultaneous monitoring of CSD and PRx in patients with aSAH.

Decreased Flow Velocity with Transcranial Color-Coded Duplex Sonography Correlates with Delayed Cerebral Ischemia due to Peripheral Vasospasm of the Middle Cerebral Artery.

BACKGROUND AND OBJECTIVE: Despite intensive therapy, vasospasm remains a major cause of delayed cerebral ischemia (DCI) in worsening patient outcome after aneurysmal subarachnoid hemorrhage (aSAH). Transcranial Doppler (TCD) and transcranial color-coded duplex sonography (TCCS) are noninvasive modalities that can be used to assess vasospasm. However, high flow velocity does not always reflect DCI. The purpose of this study was to investigate the utility of TCD/TCCS in decreasing permanent neurological deficits. METHODS: We retrospectively enrolled patients with aSAH who were treated within 72 hours after onset. TCCS was performed every day from days 4 to 14. Peak systolic velocity (PSV), mean velocity (MV), and pulsatility index were recorded and compared between DCI and non-DCI patients. In patients with DCI, endovascular therapy was administered to improve vasospasm, which led to a documented change in velocity. RESULTS: Of the 73 patients, 7 (9.6%) exhibited DCI. In 5 of the 7 patients, DCI was caused by vasospasm of M2 or the more peripheral middle cerebral artery (MCA), and the PSV and MV of the DCI group were lower than those of the non-DCI group after day 7. Intra-arterial vasodilator therapy (IAVT) was performed for all patients with DCI immediately to increase the flow volume by the next day. CONCLUSIONS: Increasing flow velocity cannot always reveal vasospasm excluding M1. In patients with vasospasm of M2 or more distal arteries, decreasing flow velocity might be suggestive of DCI. IAVT led to increases in the flow velocity through expansion of the peripheral MCA.

Importance of Early Postoperative Body Temperature Management for Treatment of Subarachnoid Hemorrhage.

BACKGROUND: The importance of acute-phase brain temperature management is widely accepted for prevention of exacerbation of brain damage by a high body temperature. METHODS: In this study, we investigated the influence of body temperature in the early postoperative period on the outcomes of 62 patients with subarachnoid hemorrhage who were admitted to our department. Body temperature was measured from day 4 to day 14 after onset. The patients were divided into those treated with surgical clipping (clip group) and coil embolization (coil group), those graded I-III (mild) and IV-V (severe) based on the Hunt & Hess classification on admission, those with and without development of delayed cerebral ischemia (DCI), and those with favorable and poor outcomes. Body temperatures throughout the hospital stay were compared in each group. RESULTS: There was no significant difference in body temperature between the clip and coil groups or between the mild and severe groups, but body temperature was significantly higher in patients with DCI compared to those without DCI, and in patients with a poor outcome compared to those with a favorable outcome. CONCLUSIONS: Fever in the early postoperative period of subarachnoid hemorrhage is associated with development of DCI and a poor outcome.

Histological Characterization of the Tumorigenic "Peri-Necrotic Niche" Harboring Quiescent Stem-Like Tumor Cells in Glioblastoma.

BACKGROUND: Characterization of the niches for stem-like tumor cells is important to understand and control the behavior of glioblastomas. Cell-cycle quiescence might be a common mechanism underlying the long-term maintenance of stem-cell function in normal and neoplastic stem cells, and our previous study demonstrated that quiescence induced by hypoxia-inducible factor (HIF)-1α is associated with a high long-term repopulation capacity of hematopoietic stem cells. Based on this, we examined human astrocytoma tissues for HIF-1α-regulated quiescent stem-like tumor cells as a candidate for long-term tumorigenic cells and characterized their niche histologically. METHODS: Multi-color immunohistochemistry was used to visualize HIF-1α-expressing (HIF-1α+) quiescent stem-like tumor cells and their niche in astrocytoma (WHO grade II-IV) tissues. This niche was modeled using spheroids of cultured glioblastoma cells and its contribution to tumorigenicity was evaluated by sphere formation assay. RESULTS: A small subpopulation of HIF-1α+ quiescent stem-like tumor cells was found in glioblastomas but not in lower-grade astrocytomas. These cells were concentrated in the zone between large ischemic necroses and blood vessels and were closer to the necrotic tissues than to the blood vessels, which suggested that a moderately hypoxic microenvironment is their niche. We successfully modeled this niche containing cells of HIF-1α+ quiescent stem-like phenotype by incubating glioblastoma cell spheroids under an appropriately hypoxic condition, and the emergence of HIF-1α+ quiescent stem-like cells was shown to be associated with an enhanced sphere-forming activity. CONCLUSIONS: These data suggest that the "peri-necrotic niche" harboring HIF-1α+ quiescent stem-like cells confers a higher tumorigenic potential on glioblastoma cells and therefore may be a therapeutic target to control the behavior of glioblastomas.

Inhibition of Fatty Acid Synthase Decreases Expression of Stemness Markers in Glioma Stem Cells.

Cellular metabolic changes, especially to lipid metabolism, have recently been recognized as a hallmark of various cancer cells. However, little is known about the significance of cellular lipid metabolism in the regulation of biological activity of glioma stem cells (GSCs). In this study, we examined the expression and role of fatty acid synthase (FASN), a key lipogenic enzyme, in GSCs. In the de novo lipid synthesis assay, GSCs exhibited higher lipogenesis than differentiated non-GSCs. Western blot and immunocytochemical analyses revealed that FASN is strongly expressed in multiple lines of patient-derived GSCs (G144 and Y10), but its expression was markedly reduced upon differentiation. When GSCs were treated with 20 µM cerulenin, a pharmacological inhibitor of FASN, their proliferation and migration were significantly suppressed and de novo lipogenesis decreased. Furthermore, following cerulenin treatment, expression of the GSC markers nestin, Sox2 and fatty acid binding protein (FABP7), markers of GCSs, decreased while that of glial fibrillary acidic protein (GFAP) expression increased. Taken together, our results indicate that FASN plays a pivotal role in the maintenance of GSC stemness, and FASN-mediated de novo lipid biosynthesis is closely associated with tumor growth and invasion in glioblastoma.

Strategies and Pitfalls of Motor-Evoked Potential Monitoring during Supratentorial Aneurysm Surgery.

BACKGROUND: The aims of this study were to reveal the strategies and pitfalls of motor-evoked potential (MEP) monitoring methods during supratentorial aneurysm surgery, and to discuss the drawbacks and advantages of each method by reviewing our experiences. METHODS: Intraoperative MEP monitoring was performed in 250 patients. Results from 4 monitoring techniques using combinations of 2 stimulation sites and 2 recording sites were analyzed retrospectively. RESULTS: MEP was recorded successfully in 243 patients (97.2%). Direct cortical stimulation (DCS)-spinal recorded MEP (sMEP) was used in 134 patients, DCS-muscle recorded MEP (mMEP) in 97, transcranial electrical stimulation (TES)-mMEP in 11 and TES-sMEP in 1. TES-mMEP during closure of the skull was used in 21 patients. DCS-mMEP was able to detect waveforms from upper and/or lower limb muscles. Alternatively, DCS-sMEP (direct [D]-wave) could accurately estimate amplitude changes. A novel "early warning sign" indicating ischemia was found in 21 patients, which started with a transiently increased amplitude of D-wave and then decreased after proximal interruption of major arteries. False-negative findings in MEP monitoring in 2 patients were caused by a blood insufficiency in the lenticulostriate artery and by a TES-sMEP recording, respectively. CONCLUSIONS: The results of this study suggest that to perform accurate MEP monitoring, DCS-mMEP or DCS-sMEP recording should be used as the situation demands, with combined use of TES-mMEP recording during closure of the skull. DCS-sMEP is recommended for accurate analysis of waveforms. We also propose a novel "early warning sign" of blood insufficiency in the D-wave.