Clinical Significance of Carotid Endarterectomy and Carotid Artery Stenting in Older Patients Over 80.

As the average life expectancy increases, neurosurgeons are likely to encounter patients aged 80 years and above with carotid stenosis; however, whether old age affects clinical post-treatment outcomes of carotid endarterectomy (CEA) or carotid artery stenting (CAS) remains inconclusive. Thus, this study aimed to evaluate the outcomes following CEA or CAS in patients aged 80 years and above. This study included older over 80 years (n = 34) and younger patients (<80 years; n = 222) who underwent CEA or CAS between 2012 and 2022. All of them were followed up for a mean of 55 months. All-cause mortality, the incidence of vascular events, ability to perform daily activities, and nursing home admission rates were assessed. During follow-up periods, 34 patients (13.3%) died due to coronary artery disease, malignancy, and pneumonia, and the incidence was significantly higher in the elderly group than in the younger group (P = 0.03; HR, 3.01; 95% CI, 1.53-5.56). The incidence of vascular events did not differ between the older group (29.5%) and the younger group (26.9%, P = 0.58); however, the incidence was significantly higher in patients with high-intensity plaques than in those without that (P = 0.008; HR, 2.83, 95%CI, 1.27-4.87). The decline in the ability to perform daily activities and increased nursing home admission rates were high in elderly patients (P < 0.01). Although the mortality rate was higher in the elderly group, subsequent vascular events were comparable to that in the younger group. The results suggest that CEA and CAS are safe and useful treatments for carotid stenosis in older patients, especially to prevent ipsilateral ischemic stroke.

Effects of superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis on the cerebrospinal fluid gas tensions and pH in hemodynamically compromised patients.

PURPOSE: This study was aimed to directly measure cerebrospinal fluid (CSF) gas tensions and pH before and after STA-MCA anastomosis for occlusive carotid artery diseases to investigate its direct effects on the ischemic brain. METHODS: This study included 9 patients who underwent STA-MCA anastomosis on the basis of CBF studies. About 1 mL of CSF was collected before and after bypass procedures, and CSF pH, CSF PO2, and CSF PCO2 were measured with a blood gas analyzer. As the controls, the CSF was collected from 6 patients during surgery for unruptured cerebral aneurysm. CSF PO2 and CSF PCO2 were expressed as the ratio to PaO2 and PaCO2, respectively. RESULTS: Before bypass procedure, CSF PO2/PaO2 was 0.88 ± 0.16, being lower than the controls (1.10 ± 0.09; P = 0.005). CSF PCO2/PaCO2 was 0.93 ± 0.13, being higher than the controls (0.84 ± 0.06; P = 0.039). Ipsilateral-to-contralateral CBF ratio had a positive correlation with CSF PO2/PaO2 (P = 0.0028) but a negative correlation with the CSF PCO2/PaCO2 (P = 0.0045). STA-MCA anastomosis increased CSF pH from 7.402 ± 0.133 to 7.504 ± 0.126 (P = 0.0011) and CSF PO2/PaO2 from 0.88 ± 0.16 to 1.05 ± 0.26 (P = 0.018) but decreased CSF PCO2/PaCO2 from 0.93 ± 0.13 to 0.70 ± 0.17 (P = 0.0006). CONCLUSION: The severity of cerebral ischemia before surgery is intensely reflected in the gas tensions and pH of the CSF. STA-MCA anastomosis carries dramatic effects on CSF gas tensions and pH in hemodynamically compromised patients. CSF would be a valuable surrogate biomarker to monitor the severity of cerebral ischemia.

Coil embolization for post-bypass aneurysm of middle meningeal artery for moyamoya disease - preservation of transdural anastomosis.

Background: Middle meningeal artery (MMA) pseudoaneurysm following revascularization surgery for moyamoya disease (MMD) is rare. Case Description: Here, a 29-year-old man presented with an MMA pseudoaneurysm after he underwent revascularization surgery (superficial temporal artery-to-middle cerebral artery bypass and encephalo-duro-myoarterio-pericranial synangiosis) for hemorrhagic MMD. At 3 months post-surgery, digital subtraction angiography showed a pseudoaneurysm in the right MMA. Transdural anastomosis to the parietal and occipital lobes was opacified at the distal MMA of the pseudoaneurysm. Intra-aneurysmal coil embolization was performed for preservation of transdural anastomosis. The postoperative course was uneventful. At 1 month post-embolization, angiography revealed an entirely occluded pseudoaneurysm. Conclusion: An increase in blood flow in the MMA due to bypass surgery may accelerate aneurysm development by increasing the hemodynamic stress. This case suggested that intra-aneurysmal embolization may be a potential treatment.

Late-onset, first-ever involuntary movement after successful surgical revascularization for pediatric moyamoya disease - Report of two cases.

Background: A small number of children with Moyamoya disease develop involuntary movements as an initial presentation at the onset, which usually resolves after effective surgical revascularization. However, involuntary movements that did not occur at the onset first occur after surgery in very rare cases. In this report, we describe two pediatric cases that developed involuntary movements during the stable postoperative period after successful surgical revascularization. Case Description: A 10-year-old boy developed an ischemic stroke and successfully underwent combined bypass surgery. However, he developed chorea six months later. Another 8-year-old boy developed a transient ischemic attack and successfully underwent combined bypass surgery. However, he developed chorea three years later. In both cases, temporary use of haloperidol was quite effective in resolving the symptoms, and involuntary movements did not recur without any medication during follow-up periods of up to 10 years. Conclusion: Postoperative first-ever involuntary movement is very rare in pediatric moyamoya disease, and the underlying mechanisms are still unclear, but a temporary, reversible imbalance of excitatory and inhibitory circuits in the basal ganglia may trigger the occurrence of these rare symptoms. Careful follow-up would be mandatory.

Thin calcification (< 2 mm) can highly predict intraplaque hemorrhage in carotid plaque: the clinical significance of calcification types.

PURPOSE: Calcification pathogenesis and the relationship between calcification and plaque composition remain unclear. This study explored the calcification characteristics of vulnerable plaques, especially focusing on calcification thickness, using computed tomography angiography and magnetic resonance plaque imaging. METHODS: Demographic, computed tomography angiography, and magnetic resonance plaque imaging data were acquired from 178 patients with 229 lesions diagnosed with carotid stenosis. The calcification types were categorized by calcification thickness. We evaluated their features, including the anatomical location and the plaque composition compared with MR plaque imaging, and clarify the clinical characteristics. Furthermore, an immunohistochemical subgroup analysis was performed on 84 lesions treated with carotid endarterectomy. RESULTS: The result of the ROC analysis suggested the threshold between symptomatic and asymptomatic calcification was 2.04 mm (AUC;0.841, 95%CI; 0.771-0.894). Calcification with ≥ 2 mm thickness was classified as thick calcification and < 2 mm thickness as thin calcification. Multivariate analysis suggested the prevalence of symptomatic patients in the thin calcification group was significantly higher than others (P = 0.01; odds ratio, 4.1; 95% confidence interval 2.8-7.2). Plaques with thin calcification were associated with plaque with intraplaque hemorrhage (P < 0.01). The interobserver reliability (κ) of calcification type was 0.962 (95% confidence interval, 0.941-0.988). Immunohistochemical analysis demonstrated that the numbers of CD68-positive cells and CD31-positive microvessels in shoulder lesions were significantly higher in the thin calcification group than in the non-thin group (both P < 0.01). CONCLUSIONS: Thin calcification was associated with plaques with intraplaque hemorrhage and had different clinical implications than thick calcification.

A case of intestinal perforation with a residual shunt tube placed during childhood: should we remove the non-functioning tube?

We report a 22-year-old man who had abdominal shunt tube migration into colon. He was diagnosed with pilocytic astrocytoma at optic-chiasm to hypothalamus at age of 7, and treated by resection, chemotherapy, and irradiation. He developed hydrocephalus and had multiple ventriculo-peritoneal shunt surgery. At age of 19, he fell in coma due to the subarachnoid and intra-ventricular hemorrhage due to the aneurysm rupture. The ventricle tube was removed, leaving the shunt valve and abdominal tube. The new shunt system was reconstructed at the contralateral side. He was at bed rest after this episode. At age of 20, he had high fever unable to control with antibiotics. The abdominal computed tomogram showed the shunt tube migration in the descending colon. The tube was removed under laparoscopy, and the inflammation was cured. The abandoned peritoneal shunt tube should be removed in patients with high tube migration risks.

Oro-mandibular dystonia in pediatric moyamoya disease: Two cases report.

BACKGROUND: In this report, we describe rare two pediatric cases that developed oro-mandibular dystonia due to moyamoya disease. CASE DESCRIPTION: A 7-year-old boy presented with oro-mandibular dystonia and transient weakness of the left extremities, and was diagnosed as moyamoya disease. Another 7-year-old boy developed oro-mandibular dystonia alone and was diagnosed as moyamoya disease. In both, cerebral blood flow (CBF) was markedly decreased in the involved hemispheres, including the basal ganglia and cerebral cortex. They successfully underwent combined bypass surgery and experienced no further attacks of oromandibular dystonia during follow-up periods. CBF almost normalized through surgical collaterals through direct and indirect bypass. CONCLUSION: When treating patients with oro-mandibular dystonia, moyamoya disease should be listed as one of the differential diseases. The underlying mechanism of oro-mandibular dystonia in moyamoya disease is still unclear, but persistent cerebral ischemia in the basal ganglia and/or parietal lobe may play a key role to induce this rare symptom.

Ameliorative Effects of Combined Revascularization Surgery on Abnormal Collateral Channels in Moyamoya Disease.

OBJECT: Abnormal collateral channels, so-called moyamoya vessels, play a critical role to compensate cerebral ischemia, but carry the risk for hemorrhagic stroke in moyamoya disease (MMD). The present study was aimed to clarify if superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and encephalo-myo-duro-arterio-pericranial synangiosis (EDMAPS) can efficiently regress the abnormal collateral channels in MMD patients. METHODS: This study included 92 hemispheres of 61 MMD patients who underwent STA-MCA anastomosis combined with EDMAPS between 2013 and 2019. There were 17 children and 44 adults. We retrospectively analyzed the findings on cerebral angiography before and 3 to 6 months after surgery, including Suzuki's angiographical stage, the development of surgical collaterals, and the extent of abnormal collateral channels such as lenticulostriate, thalamic, and choroidal channels. RESULTS: Following surgery, no pediatric and adult patients experienced any stroke during follow-up periods (40.2±25.5 and 54.9±19.7 months, respectively). Suzuki's stage significantly advanced in both adult and pediatric patients after surgery (P=0.042 and P<0.001). In adult patients, all of the lenticulostriate, thalamic, and choroidal channels significantly regressed after surgery (P<0.001, P=0.012, and P=0.004, respectively). In pediatric patients, however, lenticulostriate and choroidal channels significantly regressed (P=0.005 and P=0.034, respectively). Correlation analysis revealed that the development of surgical collaterals determined the postoperative regression of choroidal channels (P<0.001). CONCLUSION: STA-MCA anastomosis and EDMAPS may be one of the most effective procedures to widely provide surgical collaterals to the operated hemispheres and prevent not only ischemic but also hemorrhagic stroke by regressing the hemorrhage-prone abnormal collateral channels in MMD.

Specific clinical features and one-stage revascularization surgery for moyamoya disease with severe cerebral ischemia in the territory of posterior cerebral artery.

BACKGROUND: There are no reports describing the surgical procedure for moyamoya disease (MMD) patients with severe cerebral ischemia in the territory of the posterior cerebral artery (PCA) at initial presentation. In this study, therefore, we describe their clinical and radiological features and clinical results of one-stage revascularization surgery for both anterior and posterior circulation. METHODS: This study included 6 MMD patients who had severe cerebral ischemia in the PCA territory and underwent one-stage revascularization surgery for both anterior and posterior circulation. Of these, one patient underwent it on both sides. Their clinical and radiological data were precisely analyzed. Compared with usual procedure, craniotomy was extended towards the temporo-parietal area more widely. The parietal branch of superficial temporal artery (STA) was anastomosed to the angular or posterior temporal artery, while the frontal branch was anastomosed to the frontal branch of MCA. Ultimate indirect bypass was added. Their clinical and radiological outcomes were evaluated. RESULTS: Their neurological symptoms included visual and speech disturbance as well as numbness of the extremities. Cerebral infarct was distributed in the posterior temporal, parietal, and/or occipital lobe. Cerebral hemodynamics and metabolism were also impaired in the same regions. These findings were completely different from those in MMD patients without PCA lesion. Postoperative course was uneventful, and none of them recurred stroke during a mean follow-up period of 10.5 years. Surgical collaterals widely provided blood flow to the entire hemispheres, including the occipital lobe. Cerebral hemodynamics and metabolism markedly improved after surgery. CONCLUSION: One-stage revascularization surgery for both anterior and posterior circulation is feasible and effective to prevent future stroke in MMD patients with severe cerebral ischemia in the PCA territory at initial presentation.

Late (5-20 years) outcomes after STA-MCA anastomosis and encephalo-duro-myo-arterio-pericranial synangiosis in patients with moyamoya disease.

OBJECTIVE: Surgical revascularization is known to reduce the incidence of further ischemic and hemorrhagic events in patients with moyamoya disease, but the majority of previous studies report only short-term (< 5 years) outcomes. Therefore, in this study the authors aimed to evaluate late (5-20 years) outcomes of moyamoya patients after superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and indirect bypass (encephalo-duro-myo-arterio-pericranial synangiosis [EDMAPS]). METHODS: Cumulative incidences of late morbidity/mortality and disease progression were evaluated among 93 patients who underwent STA-MCA anastomosis and EDMAPS. All of the patients were prospectively followed up for longer than 5 years postsurgery (10.5 ± 4.4 years). There were 35 pediatric and 58 adult patients. Initial presentation included transient ischemic attack/ischemic stroke in 80 patients and hemorrhagic stroke in 10 patients, and 3 patients were asymptomatic. Surgery was performed in a total of 141 hemispheres. Follow-up MRI/MRA was performed within a 6- or 12-month interval during the follow-up periods. RESULTS: During the follow-up periods, 92/93 patients were free from any stroke or death, but 1 patient had a recurrence of hemorrhagic stroke (0.10% per patient-year). Disease progression occurred in the territory of the contralateral carotid or posterior cerebral artery (PCA) in 19 hemispheres of 15 patients (1.5% per patient-year). The interval between initial surgery and disease progression varied widely, from 0.5 to 15 years. Repeat bypass surgery for the anterior and posterior circulation resolved ischemic attacks in all 10 patients. CONCLUSIONS: The study results indicate that STA-MCA anastomosis and EDMAPS would be the best choice to prevent further ischemic and hemorrhagic stroke for longer than 10 years on the basis of the demonstrated widespread improvement in cerebral hemodynamics in both the MCA and ACA territories in the study patients. However, after 10 years postsurgery regular follow-up is essential to detect disease progression in the territory of the contralateral carotid artery and PCA and prevent late cerebrovascular events.

[The Analysis of the Thickness of a Cerebral Aneurysm:Can Predict the Translucent-type of Unruptured Middle Cerebral Artery Aneurysm Preoperatively?]

OBJECT: The rupture risk of cerebral aneurysms is determined by various factors. However, it is not clear whether the thickness of the aneurysm wall also influences the rupture risk. In this study, under the assumption that thin-walled aneurysms have a higher rupture risk compared with thick-wall aneurysms, we evaluate the usefulness of computed fluid dynamics(CFD)to identify thin-walled cerebral aneurysms. METHODS: Fifty-four unruptured middle cerebral aneurysms from 53 patients were analyzed using CFD before the operation. We divided these aneurysms into two groups: translucent-type aneurysms and others. To analyze the difference of these groups, individual elements(age, gender, volume, and aspect ratio)and hemodynamic factors(wall shear stress[WSS], flow coefficient, and flow coefficient per volume)were examined using CFD. RESULTS: Univariate analysis detected significant relationships between the translucent-type aneurysms and gender, aspect ratio, WSS and flow coefficient per volume. Multiple logistics regression also identified a significant relationship with gender and flow coefficient per volume. The receiver operating characteristic curve demonstrated that the flow coefficient per volume could predict translucent-type aneurysms(area under the curve 0.84, cut-off value 1.32, sensitivity 76.2%, and specificity 87.9%). CONCLUSION: Gender and the flow coefficient per volume could predict translucent-type aneurysms of the middle cerebral artery. CFD analysis might be a useful tool to predict translucent-type aneurysms.

Using postoperative remodeling of donor arteries on MR angiography to predict the development of surgical collaterals in moyamoya disease.

OBJECTIVE: The calibers of donor arteries can change dynamically after bypass surgery in patients with moyamoya disease (MMD). The present study aimed to evaluate the cutoffs of caliber changes in donor arteries associated with good surgical revascularization and to assess the impact of clinical factors potentially related to bypass development. METHODS: The authors studied 71 hemispheres of 30 adults and 16 children with MMD who underwent combined direct and indirect revascularization. They quantitatively measured the calibers of the superficial temporal artery (STA), deep temporal artery (DTA), and middle meningeal artery (MMA) with MR angiography (MRA) source images and calculated the postoperative caliber change ratios (CCRs) to assess direct and indirect bypass development. These values were compared with the findings of digital subtraction angiography, in which revascularization areas were categorized into 3 groups (poor, good, and excellent). RESULTS: In both adult and pediatric hemispheres, the median STA and DTA CCRs were higher in better-revascularization groups (p < 0.05), while MMA CCRs were not significantly different among the groups. Receiver operating characteristic analysis revealed that the cutoff STA CCRs of > 1.1 and > 1.3 were associated with good direct revascularization in adult and pediatric hemispheres, respectively. Cutoff DTA CCRs of > 1.6 and > 1.2 were associated with good indirect revascularization in adult and pediatric hemispheres, respectively. Considering these cutoff values, STA and DTA CCRs showed high median values, irrespective of age, severity of cerebrovascular reserve, disease stage, and disease-onset type. CONCLUSIONS: Caliber changes in STAs and DTAs can be easily measured using MRA, and they could be indicators of direct and indirect bypass development. The dual development of a direct and indirect bypass was most frequently observed in the context of a combined bypass procedure in both adults and children with MMD.

Strategy and effect of repeat bypass surgery for anterior/posterior circulation in refractory moyamoya disease.

OBJECTIVE: In this study the authors aimed to describe clinical features, surgical techniques, and long-term outcomes of repeat bypass surgery required for a certain subset of patients with moyamoya disease. METHODS: The authors retrospectively reviewed a total of 22 repeat bypass surgeries for 20 patients (age range 1-69 years) performed during the last 20 years at their institutions. The patients were classified into 2 groups. Group A included 10 patients who underwent repeat bypass surgery for anterior circulation due to insufficient revascularization on the ipsilateral side. Group B included 10 patients who underwent repeat bypass surgery for posterior circulation due to the involvement of the posterior cerebral artery (PCA) after successful initial surgery for anterior circulation. RESULTS: Preoperative symptoms included headache in 3 patients, transient ischemic attack in 10, cerebral infarction in 3, and intracranial hemorrhage in 4 patients. Intervals between the initial bypass surgery and repeat bypass surgery were 0.3-30 years (median 3 years). In group A, superficial temporal artery to middle cerebral artery (MCA) anastomosis and indirect bypass were performed on 7 hemispheres. Only indirect bypass was performed on 3 hemispheres because of the lack of suitable donor or recipient arteries. In group B, occipital artery (OA) to PCA anastomosis and indirect bypass were conducted on 4 hemispheres, and OA-MCA anastomosis and indirect bypass on 1 hemisphere. Only indirect bypass was conducted on 7 hemispheres because of the lack of suitable recipient arteries. All 22 repeat bypass surgeries were successfully conducted. During follow-up periods (median 4 years), none of the patients suffered repeat stroke except 1 patient who died of recurrent intracerebral hemorrhage 3 years after repeat bypass surgery for anterior circulation. CONCLUSIONS: Repeat bypass surgery was feasible and effective to reduce further incidence of headache attack, transient ischemic attack, and ischemic/hemorrhagic stroke in moyamoya disease patients. Through precise radiological analysis, surgical procedures should be planned to yield maximal therapeutic effects.

Persistent Primitive Olfactory Artery as Novel Collateral Channel to the Anterior Cerebral Artery in Moyamoya Disease.

BACKGROUND: There are a variety of collateral routes to compensate persistent cerebral ischemia in moyamoya disease. However, there is no report presenting the persistent primitive olfactory artery (POA) as a spontaneous collateral route to the anterior cerebral artery (ACA) in moyamoya disease. METHODS: We precisely examined cerebral angiography in 84 patients with moyamoya disease to identify the collateral channel through the persistent POA. Its anatomy was evaluated on pre- and postoperative angiography. RESULTS: Of 84 patients, four (4.8%) had spontaneous collateral channel through the persistent POA. All of these four hemispheres were categorized into Stage 5. In all four patients, the collateral blood flow arose from the ophthalmic artery and run to the persistent POA through the ethmoidal moyamoya. The persistent POA provided collateral blood flow from the ophthalmic artery to the ACA in all four patients. Superficial temporal artery to middle cerebral artery anastomosis and encephalo-duro-myo-arterio-pericranial synangiosis was performed in three of four patients. After surgery, the collateral channel through the persistent POA completely disappeared or markedly regressed, suggesting a significant improvement of cerebral hemodynamics in the territory of not only the MCA but also the ACA. CONCLUSION: The persistent POA can potentially provide collateral blood flow to the ACA in about 5% of patients with moyamoya disease, and should be recognized as a novel collateral channel in moyamoya disease. The persistent POA may be useful to evaluate therapeutic effects of surgical revascularization on the ACA territory.

Hypoxia accelerates intraplaque neovascularization derived from endothelial progenitor cells in carotid stenosis.

OBJECTIVE: The relationship between intraplaque hypoxia and intraplaque hemorrhage (IPH) has been reported, but the details remain obscure. In this study, the authors aimed to clarify the relationship among intraplaque hypoxia, endothelial progenitor cells (EPCs), and neovascularization, which causes IPH. The histological findings of specimens obtained from carotid endarterectomy were assessed. METHODS: This study included 49 patients who underwent carotid endarterectomy. Magnetic resonance plaque imaging was performed to analyze the components of the carotid plaques, and surgical specimens were subjected to immunohistochemical analysis. The numbers of hypoxia-inducible factor-1 alpha (HIF-1α)-, CD34-, CD133-, and vascular endothelial growth factor receptor-2 (VEGFR-2)-positive cells in the carotid plaques were precisely quantified, as were the number and maximum diameter of CD31-positive microvessels. RESULTS: Plaque components were judged as fibrous in 7 samples, lipid-rich in 22, and IPH in 20. The number of CD34-, VEGFR-2-, and CD133-positive cells as an EPC-specific marker was significantly correlated with the number of HIF-1α-positive cells (r = 0.9, r = 0.82, and r = 0.81, respectively). These numbers varied among the 3 plaque components (IPH > lipid-rich > fibrous). The number and maximum luminal diameter of CD31-positive microvessels were also significantly correlated with the number of HIF-1α-positive cells (r = 0.85 and r = 0.89, respectively) and varied among the 3 plaque components (IPH > lipid-rich > fibrous). CONCLUSIONS: The present findings suggest that intraplaque hypoxia may accelerate abnormal microvessel formation derived from EPCs, which in turn promotes IPH. The results also suggest that microvessel enlargement is a pivotal characteristic of IPH and these enlarged microvessels are immature endothelial tubes with disorganized branching and are fragile and prone to rupture.

[Ultrasound-aided Fixation of a Biodegradable Cranial Fixation System:SonicWeld Rx® System in Pediatric Neurosurgery].

PURPOSE: Ultrasound-aided fixation of a biodegradable cranial fixation system called SonicWeld Rx®, has been widely applied in the fields of craniofacial surgery and plastic surgery. However, there are few reports that denote its use in the field of neurosurgery. This study aimed to evaluate the usefulness of SonicWeld Rx® system in pediatric neurosurgery. METHODS: This study included 11 pediatric patients(10 boys, 1 girl), who underwent craniotomy for moyamoya disease, brain tumor, and arachnoid cyst. Their mean age was 6.4 years, ranging from 4 to 10 years. LactoSorb® system was applied in 6 patients and SonicWeld Rx® system in 5. RESULTS: The time required for screw fixation was significantly shorter in the SonicWeld group(6.5±1.4sec)than in the LactoSorb group(13.4±2.8sec), with p<0.05. The quality of fixation strength was adequate in both groups. There were no perioperative complications related to the absorbable fixation device. A 3-D skull CT detected no malposition of the bone flap 3 months postoperatively. There were no scalp complications noted for an average of 21 months. CONCLUSION: SonicWeld Rx® system can be easy and useful in fixing the bone flap to the cranium in the field of pediatric neurosurgery.

[Computational Fluid Dynamic Analysis of Intracranial Aneurysms Using Newly Developed Software:Can It Predict the Thin-Walled Region of Intracranial Aneurysm Preoperatively?]

OBJECT: Recent studies have shown that computational fluid dynamics(CFD)analysis is useful to evaluate flow dynamics of intracranial aneurysms. However, CFD analysis still requires high costs and substantial time even now. This study aimed to evaluate whether newly developed software can shorten the time for analysis and serve useful information during clipping surgery for intracranial aneurysms. METHODS: CFD analysis was performed in 55 unruptured cerebral aneurysms in 51 patients. The time required for analysis of each aneurysm was recorded. On the basis of CFD analysis, both pressure and wall shear stress(WSS)were calculated as the values at the systolic and diastolic phases, and also the mean value through one cardiac cycle. These data were compared between thin-wall points and other points within each aneurysm. RESULTS: The average time required for analysis was 3 hours, ranging from 1 to 15 hours. The CFD data could be referenced during surgery in each patient. The pressure in about 93% and 80% of the thin-wall points was higher than that at other points within each aneurysm in the systolic and diastolic phases, respectively. However, there was no significant correlation between WSS and wall thickness in each aneurysm. CONCLUSION: This study clearly shows that newly-developed software is simple and requires much shorter time for CFD analysis than previous methods. Higher pressure through the cardiac cycle may efficiently predict a thin-wall region within intracranial aneurysms, which strongly suggests that CFD analysis would be a valuable tool to determine the treatment strategy in patients with unruptured aneurysms.

Impact of a novel biomarker, T-LAK cell-originating protein kinase (TOPK) expression on outcome in malignant glioma.

This study aimed to evaluate the biological features of T-lymphokine-activated killer cell-originating protein kinase (TOPK) in vitro and to assess clinical impact of TOPK on the outcome in patients with malignant glioma. TOPK protein level and TOPK mRNA and protein levels in six glioma cell lines were examined using Western blot and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Immunohistochemistry was performed to examine their subcellular localization of TOPK. Using surgical specimens from 57 patients with gliomas, TOPK and Ki-67 expressions were examined by immunohistochemistry. Their co-localization was also examined with double immunofluorescence immunohistochemistry. Impacts of TOPK/Ki-67 expression on the overall survival (OS) and progression-free survival (PFS) in 32 patients with glioblastoma multiforme (GBM) were examined, using Kaplan-Meier and Cox proportion hazard models. Immunohistochemistry revealed that approximately 20-30% of glioma cells were positive for TOPK in vitro. TOPK mRNA was identified in all glioma cell lines on RT-PCR. The value of TOPK/GAPDH was 0.27 ± 0.11. TOPK and Ki-67 expressions were significantly higher in GBM patients than in non-GBM patients. A majority of TOPK-positive cells were also positive for Ki-67 and vice versa. Multivariate analysis revealed that a low TOPK expression (≤ 12.7%) was an independent predictor of longer OS (P = 0.0372), and that gross total removal and a low TOPK expression (≤ 12.7%) were independent predictors of longer PFS (P = 0.0470 and P = 0.0189, respectively). The findings strongly suggest biological and clinical importance of TOPK expression in gliomas, indicating a novel therapeutic potential of TOPK inhibitors to treat malignant gliomas.

Downregulation of Apolipoprotein-E and Apolipoprotein-J in Moyamoya Disease-A Proteome Analysis of Cerebrospinal Fluid.

BACKGROUND AND PURPOSE: Genetic factors are closely involved in the etiology of moyamoya disease (MMD). However, its postgenomic mechanisms are still unknown. This study was aimed to identify specific biomarkers in the cerebrospinal fluid (CSF) of patients with MMD, using quantitative proteome technique. METHODS: This study included 10 patients with MMD and 4 controls. The CSF was collected without blood contamination during surgery. A comparative 2-dimensional gel electrophoresis study (2D-PAGE) was performed. Protein spots that showed significant differences between moyamoya patients and controls were selected for further analysis by mass spectrometry. RESULTS: On 2D-PAGE, 2 proteins were significantly upregulated, and 2 other proteins were downregulated in the CSF of MMD. Further mass spectrometry analysis revealed that haptoglobin and α-1-B-glycoprotein (A1BG) were upregulated. On the other hand, apolipoprotein-E (apoE), apoE precursor, and apolipoprotein-J (apoJ) were significantly downregulated in the CSF of MMD. The observed probability-based MOWSE score was 72 for haptoglobin (P <.05), 521 for A1BG (P <.05), 62 for apoE (P <.05), 72 for apoE precursor (P <.05), and 112 for apoJ (P <.05). CONCLUSION: Although the role of A1BG in the central nervous system is still unknown, the overexpressed haptoglobin may indicate the inflammation and/or angiogenesis in MMD. The downregulation of apoE and apoJ strongly suggests a critical role of lipid metabolism in the development and progression of MMD. These proteins may be novel biomarkers in shedding light on the pathogenesis of MMD, although further studies would be warranted.

Berlin Grading System Can Stratify the Onset and Predict Perioperative Complications in Adult Moyamoya Disease.

BACKGROUND: The grading system for moyamoya disease is not established. OBJECTIVE: To assess the usefulness of a recently proposed grading system for stratifying the clinical severity and predicting postoperative morbidity in adult moyamoya disease. METHODS: We investigated 176 hemispheres from 89 adult patients who were diagnosed with moyamoya disease in Japan. Their data were analyzed using the Berlin grading system with minor modifications. After summarizing the numerical values for digital subtraction angiography (1-3 points), magnetic resonance imaging (0-1 points), and single-photon emission computed tomography (0-2 points), 3 grades of moyamoya disease were defined: mild (grade I) = 1 to 2 points, moderate (grade II) = 3 to 4 points, and severe (grade III) = 5 to 6 points. In total, 82 of 161 hemispheres underwent superficial temporal artery to middle cerebral artery anastomosis and indirect synangiosis. Postoperative neurological morbidity was included within 30 d after surgery. RESULTS: Preoperative examinations categorized 87 hemispheres as grade I, 39 as grade II, and 50 as grade III. There was a significant correlation between the Berlin grading system and clinical severity (P < .001). Perioperative complications occurred in 12 of 82 (14.6%) hemispheres, including transient ischemic attack in 3 hemispheres, ischemic stroke in 4 hemispheres, symptomatic hyperperfusion in 4 hemispheres, and intracerebral hemorrhage in 1 hemisphere. The Berlin grading system was related to their occurrence (P < .001). CONCLUSION: The Berlin grading system facilitates the stratification of clinical severity and predicting postoperative neurological morbidity in adult moyamoya disease, thereby suggesting its general usage in clinical practice.