Combined endoscopic endonasal and transcranial approach for internal carotid artery aneurysms: usefulness and safety of endonasal proximal control.

It is necessary to secure both the proximal and distal sides of the parent artery to prevent premature rupture when clipping cerebral aneurysms. Herein, we describe four cases in which the proximal internal carotid artery (ICA), affected by a paraclinoid aneurysm, was secured using an endoscopic endonasal approach. We used various tools, including a surgical video, cadaver dissection picture, artist's illustration, and intraoperative photographs, to elucidate the process. No patient experienced postoperative complications at our institution. Compared to the cervical or cavernous ICA, the ICA adjacent to the clivus (paraclival ICA) can be anatomically safely and easily exposed using an endoscopic endonasal approach because there is no need to consider cerebrospinal fluid leakage or hemorrhage from the cavernous sinus. Securing the proximal side of the parent artery using an endoscopic endonasal approach may be a viable method for clipping selected ICA aneurysms, such as paraclinoid aneurysms especially for upward or outward aneurysms of the C2 portion.

Computational Fluid Dynamics Analysis Features in Aneurysm Development in Rats.

The investigation of how to control the development and growth of cerebral aneurysms is important for the prevention of subarachnoid hemorrhage. Although there have been several types of research studies on computational fluid dynamics (CFD) analysis of brain aneurysm development and growth, there has been no unified interpretation of the CFD analysis results. The purpose of this study is to clarify the characteristics of CFD analysis results related to the development of cerebral aneurysms using an animal model. Nineteen rat models of cerebral aneurysms were created, and the CFD analysis results between the cerebral aneurysm group [n = 10; the aneurysm was observed on magnetic resonance angiography (MRA) within 10 weeks after aneurysm induction surgery] and the nonaneurysm group (n = 9) were compared. All aneurysms were confirmed on the proximal segment of the left cerebral artery (P1), and the cross-sectional area and curvature of the left P1 were evaluated together. In the cerebral aneurysm group, there was a decrease in wall shear stress (WSS) that is consistent with the location of the aneurysm compared to the nonaneurysm group. The cross-sectional area of the left P1 gradually increased in the aneurysm group but not in the nonaneurysm group. The mean curvature in the entire left P1 was higher in the aneurysm group than in the nonaneurysm group. This study revealed that the development of cerebral aneurysms is due to changes in vascular morphology, namely, an increase in vessel diameter and a high curvature, and a decreased WSS consistent with the site of aneurysm development using this animal model.

Microbleeds Due to Reperfusion Enhance Early Seizures after Carotid Ligation in a Rat Ischemic Model.

Impaired reperfusion in ischemic brain disease is a condition that we are increasingly confronted with owing to recent advances in reperfusion therapy. In the present study, rat models of reperfusion were investigated to determine the causes of acute seizures using magnetic resonance imaging (MRI) and histopathological specimens. Rat models of bilateral common carotid artery ligation followed by reperfusion and complete occlusion were created. We compared the incidence of seizures, mortality within 24 h, MRI, and magnetic resonance spectroscopy (MRS) to evaluate ischemic or hemorrhagic changes and metabolites in the brain parenchyma. In addition, the histopathological specimens were compared with those observed on MRI. In multivariate analysis, the predictive factors of mortality were seizure (odds ratios (OR), 106.572), reperfusion or occlusion (OR, 0.056), and the apparent diffusion coefficient value of the striatum (OR, 0.396). The predictive factors of a convulsive seizure were reperfusion or occlusion (OR, 0.007) and the number of round-shaped hyposignals (RHS) on susceptibility-weighted imaging (SWI) (OR, 2.072). The incidence of convulsive seizures was significantly correlated with the number of RHS in the reperfusion model. RHS on SWI was confirmed pathologically as microbleeds in the extravasation of the brain parenchyma and was distributed around the hippocampus and cingulum bundle. MRS analysis showed that the N-acetyl aspartate level was significantly lower in the reperfusion group than in the occlusion group. In the reperfusion model, RHS on SWI was a risk factor for convulsive seizures. The location of the RHS also influenced the incidence of convulsive seizures.

Transcranial electrical stimulation technique for induction of unilateral motor evoked potentials.

OBJECTIVE: Transcranial electrical stimulation motor evoked potentials (TES-MEP) are widely used to monitor motor function; however, broad current spread and induced body movement are limitations of this technique. We herein report a localized stimulation technique for TES-MEP that induces unilateral MEP responses. METHODS: The stimulation of C1(+)-C4(-) or C2(+)-C3(-) was performed to induce right- or left-sided muscle contraction, respectively, in 70 patients. Electromyography was recorded by placing electrodes on the bilateral abductor pollicis brevis (APB) and abductor hallucis (AH) muscles. Stimulation conditions were regulated in the range to induce unilateral muscle contractions contralateral to the anodal stimulation. The thresholds and amplitudes of TES-MEP were retrospectively analyzed. RESULTS: The thresholds of APB were lower than those of AH in 47 patients, AH thresholds were lower than those of APB in 6 patients, and both APB and AH started to respond at the same intensity in 15 patients. This technical stimulation induced contralateral limb contractions with a suprathreshold stimulation of 129.4 ± 35.6 mA (mean ± standard deviation) in 68 patients (97%). Amplitudes in the suprathreshold stimulation of APB and AH responses were 727.5 ± 695.7 and 403.3 ± 325.7 µV, respectively. CONCLUSIONS: The C1(+)-C4/C2(+)-C3(-) stimulation in TES-MEP enables a localized stimulation to induce unilateral MEP responses. SIGNIFICANCE: Our stimulation technique enables the stable and safe monitoring of unilateral limbs, and contributes to the reliable monitoring of motor function in neurosurgery.

Deep learning for the diagnosis of mesial temporal lobe epilepsy.

OBJECTIVE: This study aimed to enable the automatic detection of the hippocampus and diagnose mesial temporal lobe epilepsy (MTLE) with the hippocampus as the epileptogenic area using artificial intelligence (AI). We compared the diagnostic accuracies of AI and neurosurgical physicians for MTLE with the hippocampus as the epileptogenic area. METHOD: In this study, we used an AI program to diagnose MTLE. The image sets were processed using a code written in Python 3.7.4. and analyzed using Open Computer Vision 4.5.1. The deep learning model, which was a fine-tuned VGG16 model, consisted of several layers. The diagnostic accuracies of AI and board-certified neurosurgeons were compared. RESULTS: AI detected the hippocampi automatically and diagnosed MTLE with the hippocampus as the epileptogenic area on both T2-weighted imaging (T2WI) and fluid-attenuated inversion recovery (FLAIR) images. The diagnostic accuracies of AI based on T2WI and FLAIR data were 99% and 89%, respectively, and those of neurosurgeons based on T2WI and FLAIR data were 94% and 95%, respectively. The diagnostic accuracy of AI was statistically higher than that of board-certified neurosurgeons based on T2WI data (p = 0.00129). CONCLUSION: The deep learning-based AI program is highly accurate and can diagnose MTLE better than some board-certified neurosurgeons. AI can maintain a certain level of output accuracy and can be a reliable assistant to doctors.

Laboratory Test Predictors for Major Bleeding in Elderly (≥80 Years) Patients With Nonvalvular Atrial Fibrillation Treated With Edoxaban 15 mg: Sub-Analysis of the ELDERCARE-AF Trial.

Background We investigated the predictors related to major bleeding events during treatment with edoxaban 15 mg in patients aged ≥80 years with nonvalvular atrial fibrillation and high bleeding risk, for whom standard oral anticoagulants are inappropriate, focusing on standard laboratory tests related to bleeding. Methods and Results This was a prespecified subanalysis of the on-treatment analysis set of the ELDERCARE-AF (Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients) trial. Major bleeding was the primary safety end point. The event rates were calculated according to prespecified characteristics at baseline. A total of 984 Japanese patients were randomly assigned to edoxaban 15 mg or placebo (n=492, each). During the study period, 20 and 11 major bleeding events occurred in the edoxaban and placebo groups, respectively. The adjusted analysis revealed that hemoglobin <12.3 g/dL (adjusted hazard ratio [aHR], 3.57 [95% CI, 1.10-11.55]) and prothrombin time ≥12.7 seconds; (aHR, 2.89 [95% CI, 1.05-8.02]) independently predicted major bleeding, while creatinine clearance <30 mL/min showed a tendency towards an increase in major bleeding (aHR, 2.68; 95% CI, 0.96-7.46). In patients treated with edoxaban lacking these 3 risk factors, no major bleeding occurred; major bleeding event rates increased with each risk factor. Patients with 3 risk factors were significantly more likely to have a major bleeding event at 11.05%/year (HR, 7.15 [95% CI, 1.92-26.71]). Conclusions In elderly patients with nonvalvular atrial fibrillation with high bleeding risk, baseline hemoglobin <12.3 g/dL, prothrombin time ≥12.7 seconds, and creatinine clearance <30 mL/min may predict major bleeding during treatment with edoxaban 15 mg. Registration URL: ELDERCARE-AF https://www.clinicaltrials.gov; Unique number: NCT02801669.

Validity of Preoperative Screening Before Open-Heart Surgery in Reduction of Perioperative Ischemic Stroke.

OBJECTIVES: Cerebrovascular event after open-heart surgery is a critical complication and contributes to poor prognosis, including increased mortality. The purpose of this study is to investigate the appropriate preoperative risk assessment and monitoring for reducing the risk of ischemic stroke after open-heart surgery. MATERIALS AND METHODS: 184 patients who underwent surgery for valvular heart disease were included in this study. Near-infrared oxygen saturation monitoring (INVOS system) was performed during open-heart surgery. For the purpose of perioperative stroke risk assessment, we evaluated the clinical and radiological factors of the group that underwent preoperative consultation and the group that did not, and of the patients with and without postoperative ischemic stroke. RESULTS: Preoperative consultation was performed in 60 cases. Large vessel steno-occlusive disease was found in nine cases, of which three had undergone revascularization surgery. Cerebral infarction developed in four cases, all of which had no large vessel steno-occlusive disease. There was no significant association between the development of postoperative ischemic stroke and presence of large vessel steno-occlusive disease. Preoperative baseline INVOS value was significantly low in the ischemic stroke group (49.5 ± 12.5) compared to the non-ischemic stroke group (66.8 ± 10.0), (P = 0.012). CONCLUSIONS: In open-heart surgery for valvular heart disease, low preoperative baseline INVOS values were associated with cerebral ischemic stroke after surgery. The combination of appropriate preoperative screening for large vessel steno-occlusive disease and measurement of INVOS could be used as a simple and useful method in screening for the risk of ischemic stroke after open-heart surgery.

Asymptomatic cerebral findings on 3-Tesla MRI in patients with severe carotid artery stenoses.

BACKGROUND AND PURPOSE: Small vessel diseases (SVDs) are often asymptomatic. However, SVDs significantly influence the prognosis in patients with large vessel diseases (LVDs). We investigated asymptomatic cerebral findings on 3-Tesla MRI in patients with severe carotid artery (CA) stenoses, compared to peoples without a past history of neurological disorders, including strokes. METHODS: We retrospectively analyzed the prevalences of various asymptomatic cerebral findings which were intracerebral hemorrhages (ICHs), cortical superficial siderosis, ventricular dilatation (Evans' index) and SVDs including cerebral microbleeds (CMBs), lacunar infarctions (LIs), deep white matter hyperintensities (WMHs), periventricular hyperintensities (PVHs). The prevalence of each finding was compared using multivariate logistic regression models with adjustment for stroke risk factors. RESULTS: We evaluated the findings in 54 patients with severe CA stenosis treated by stenting (CA stenosis group) and 200 adults with health screening tests of the brain and no past history of neurological disorders (control group). Multivariate analyses adjusted for age ≥ 65 years old, female gender, hypertension, hyperlipidemia, diabetes mellitus, alcohol consumption, and smoking index revealed that the prevalences of severe PVHs, severe deep WMHs, asymptomatic deep ICHs, and asymptomatic LIs were significantly higher in the CA stenosis group than the control group. However, there were no significant differences in the prevalences of CMBs, or the remaining asymptomatic findings described above. CONCLUSIONS: With pathological differences between SVD and LVD, asymptomatic SVDs except CMBs and deep ICHs often co-exists severe CA stenosis as a presentative LVD.

Macrohistory of Moyamoya Disease Analyzed Using Artificial Intelligence.

INTRODUCTION: Moyamoya disease is characterized by progressive stenotic changes in the terminal segment of the internal carotid artery and the development of abnormal vascular networks called moyamoya vessels. The objective of this review was to provide a holistic view of the epidemiology, etiology, clinical findings, treatment, and pathogenesis of moyamoya disease. A literature search was performed in PubMed using the term "moyamoya disease," for articles published until 2021. RESULTS: Artificial intelligence (AI) clustering was used to classify the articles into 5 clusters: (1) pathophysiology (23.5%); (2) clinical background (37.3%); (3) imaging (13.2%); (4) treatment (17.3%); and (5) genetics (8.7%). Many articles in the "clinical background" cluster were published from the 1970s. However, in the "treatment" and "genetics" clusters, the articles were published from the 2010s through 2021. In 2011, it was confirmed that a gene called Ringin protein 213 (RNF213) is a susceptibility gene for moyamoya disease. Since then, tremendous progress in genomic, transcriptomic, and epigenetic profiling (e.g., methylation profiling) has resulted in new concepts for classifying moyamoya disease. Our literature survey revealed that the pathogenesis involves aberrations of multiple signaling pathways through genetic mutations and altered gene expression. CONCLUSION: We analyzed the content vectors in abstracts using AI, and reviewed the pathophysiology, clinical background, radiological features, treatments, and genetic peculiarity of moyamoya disease.

Accuracy of computed tomography: magnetic resonance imaging image fusion using a phantom for skull base surgery.

BACKGROUND: The aim of this study is to assess the positional accuracy of image fusions of the skull base region using different magnetic resonance imaging (MRI) and computed tomography (CT) image pairs. METHODS: An image set of 3D fast imaging employing steady-state acquisition-C (FIESTA-C) was used as the base image set. Image fusions were performed using an image set with different fields of view (FOVs): one with different matrix size, one with a different sequence of 3D spoiled gradient recalled acquisition, and one with different modality (CT), using a phantom including multi columnar objects. Position of columns at the center, and 4 and 8 cm from the center were measured. The displacements between the base image set and fused image set were measured. For slices with different z-positions, the displacement of the 8-cm column was assessed. For 20 clinical MRI cases, the distance between the dorsum sellae and the cranial nerves was measured. RESULTS: No significant differences were found between the different FOVs or image sequences. However, with the different matrix sizes and modalities, significant displacements were observed, although they were all within 0.5 mm. Similar displacements were observed in the slices at different z-positions. All cranial nerves were located within 40 mm of the dorsum sellae. CONCLUSIONS: The displacements following image fusion were within approximately 0.5 mm, even at 8 cm from the center. This suggests that the region where the cranial nerves are located, within 40 mm of the dorsum sellae, had no risk of positional error following image fusion.

Paroxysmal atrioventricular block induced during paroxysmal intra-atrial reentrant tachycardia.

Paroxysmal atrio-ventricular (AV) block is a relatively rare form of bradyarrhythmia that may be caused by vagal reflex, intrinsic His-Prukinje system (HPS) disorder, or idiopathic mechanisms. We report a case with paroxysmal AV block and syncopal episodes that appeared only during intra-atrial reentrant tachycardia (IART) after an ablation procedure. Syncope did not occur under sinus rhythm with stable 1:1 AV conduction. An HPS disorder was proven in an electrophysiological study. It was suggested that paroxysmal AV block was induced via a tachycardia-dependent mechanism with an exacerbation of latent HPS disorder. The occurrence of the IART was only transient, and there was no recurrent syncope during one-year follow-up. Pacemaker implantation could be avoided. .

Virtual test occlusion for assessing ischemic tolerance using computational fluid dynamics.

BACKGROUND: Ischemic tolerance has been evaluated by the balloon test occlusion (BTO) for cerebral aneurysms and tumors that might require parent artery occlusion during surgery. However, because of its invasiveness, a non-invasive evaluation method is needed. In this study, we assessed the possibility of virtual test occlusion using computational fluid dynamics (CFD) as a non-invasive alternative to BTO for evaluating ischemic tolerance. METHODS: Twenty-one patients who underwent BTO were included in the study. Virtual test occlusion was performed using CFD analysis, and the flow rate (FR) and wall shear stress (WSS) of the middle cerebral artery on the occlusion side were calculated. The correlations between these parameters and examination data including the parameters of computed tomography perfusion during BTO were assessed and the cutoff value of CFD parameters for detecting the good collateral group was calculated. RESULTS: The FR was strongly correlated with mean transit time (MTT) during BTO and moderately correlated with collateral flow grade based on angiographic appearance. The WSS was moderately correlated with collateral flow grade, mean stump pressure (MSP), and MTT. Furthermore, the FR and WSS were strongly correlated with the total FR and the diameters of the inlet vessels. The cutoff value of FR for detecting the good collateral group was 126.2 mL/min, while that of the WSS was 4.54 Pa. CONCLUSION: The parameters obtained through CFD analysis were correlated with collateral flow grade and MSP in addition to MTT. CFD analysis may be useful to evaluate ischemic tolerance as a non-invasive alternative to BTO.

Effects of polarity of bipolar sensorimotor direct cortical stimulation on intraoperative motor evoked potentials.

OBJECTIVE: The present study investigated the effects of the stimulus polarity and location of motor evoked potential (MEP) to establish a stimulation protocol. METHODS: Nineteen patients who intraoperatively underwent MEP in bipolar direct cortical stimulation were enrolled in the present study. Somatosensory evoked potentials (SEP) of the contralateral median nerve stimulation were recorded to determine stimulation sites. MEP was performed under two settings in all patients: 1. Anodal bipolar stimulation: an anode on the precentral gyrus and a cathode on the postcentral gyrus, 2. Cathodal bipolar stimulation: a cathode on the precentral gyrus and an anode on the postcentral gyrus. MEP amplitudes and the coefficient of variation (CV) at a stimulation intensity of 25 mA and the thresholds of induced MEP were compared between the two settings. RESULTS: An electrical stimulation at 25 mA induced a significantly higher amplitude in cathodal bipolar stimulation than in anodal bipolar stimulation. Cathodal bipolar stimulation also showed significantly lower thresholds than anodal stimulation. CV did not significantly differ between the two groups. CONCLUSIONS: These results indicate that cathodal bipolar stimulation is superior to anodal bipolar stimulation for intraoperative MEP monitoring. SIGNIFICANCE: MEP in cathodal bipolar cortical stimulation may be used in a safe and useful evaluation method of motor fiber damage that combines sensitivity and specificity.

Preserved arachnoid membrane acts as a predictor of postoperative visual improvement in clinoidal meningioma.

OBJECTIVES: Improvement of patient visual outcome is very important in the treatment of clinoidal meningioma (CLM). The purpose of this study is to determine the association between arachnoid preservation and visual outcome. PATIENTS: Fifteen patients with CLMs that caused visual impairment underwent surgery in our hospital. The patients included 4 men and 11 women, and the mean age was 53.3 years. METHODS: The clinical findings of these patients were retrospectively reviewed. We divided the patients into two groups based on the presence or absence of the arachnoid membrane. Group 1 comprised cases in which arachnoid preservation was intraoperatively confirmed. Group 2 comprised cases in which the arachnoid membrane was not preserved. The Landolt C chart was used to evaluate visual acuity, and dynamic visual field tests using Goldmann perimetry were used to evaluate the visual field. Results were compared before and after surgery. RESULTS: The visual acuity of the ipsilateral eye was significantly improved in Group 1 (p = 0.038). There were no other significant differences between the two groups in terms of tumor volume, patient age, and symptom duration. CONCLUSIONS: Patients in which arachnoid preservation could be intraoperatively confirmed had good improvement in visual acuity. Further research with an increased number of cases is needed to confirm these findings.

Permanent pacemaker implantation in a patient with persistent left superior vena cava with an absent right superior vena cava: A case report.

Persistent left superior vena cava (PLSVC) is a common congenital anomaly of the thoracic venous system. PLSVC affects 0.3-0.5% of the general population, with 0.09-0.13% having PLSVC with an absent right superior vena cava. A 92-year-old woman was transported to our hospital by ambulance because of syncopal attacks lasting a few seconds. Electrocardiography showed paroxysmal supraventricular tachycardia and sinus arrest for up to 10 s with syncope when the arrhythmia stopped. This occurred repeatedly, and a diagnosis of sick sinus syndrome was made. The patient was scheduled for dual-chamber permanent pacemaker implantation. She had isolated PLSVC, and pacing lead was inserted into the right atrium through the PLSVC from her left subclavian vein. The "J" pre-shaped stylet was used to introduce the lead via the tricuspid valve to the right ventricular outflow tract (RVOT) and placed in the septum of RVOT. Another lead was advanced into the right atrial appendage using the "J" pre-shaped stylet. After three years of implantation, fluoroscopy showed a stable position of pacing leads, and pacemaker interrogations showed no major changes in parameters. .

Additional Revascularization Using Multiple Burr Holes for PCA Involvement in Moyamoya Disease.

In specific cases of moyamoya disease (MMD), posterior cerebral artery (PCA) stenosis can develop after treatment of the anterior circulation and require additional revascularization. Here, we report two cases that underwent additional posterior indirect revascularization with multiple burr holes for PCA involvement after bilateral revascularization treatment of the anterior circulation. They presented with transient ischemic attack even after bilateral superficial temporal artery-middle cerebral artery bypass, and magnetic resonance angiography (MRA) showed that PCA stenosis had worsened. Indirect revascularization with multiple burr holes using Benz-marked skin incisions was performed. After surgery, the symptoms improved without perioperative complications, and cerebral angiography showed collateral circulation via the burr hole. Indirect revascularization for MMD is often combined with direct revascularization, and there are only a few reports on the use of multiple burr hole surgery alone. In addition, there are few reports of posterior circulation, despite the emphasis on the importance of PCA involvement in MMD. Indirect revascularization with multiple burr holes alone can be performed in multiple areas and applied to patients who cannot undergo direct revascularization using the occipital artery. The procedure is simple and less invasive than traditional direct revascularization procedures. Therefore, it can be effective, especially in pediatric cases of MMD with PCA involvement.

Pitfalls of Commonly Used Ischemic and Dementia Models Due to Early Seizure by Carotid Ligation.

While the bilateral common carotid artery (CCA) ligation model is widely used in cerebrovascular disease and dementia studies, it can frequently cause seizures. We examined the validity of seizure as an experimental model of ischemia. Eight-week-old male Wistar and Sprague-Dawley (SD) rats were implanted with electrocorticography (ECoG) electrodes and bilateral CCA ligation was performed and compared to the sham groups. ECoG monitoring was used to confirm the seizure discharge and count the number of spikes in the interictal phase 2 h after ligation, followed by power spectral analysis. Magnetic resonance imaging (MRI) was performed 6 h after bilateral CCA ligation to assess fractional anisotropy (FA), apparent diffusion coefficient (ADC), and cerebral blood flow (CBF) values. Magnetic resonance spectroscopy (MRS) was also performed and the ischemic parameters and electrophysiological changes were compared. The Wistar rat group had significantly higher mortality, frequency of seizures, incidence of non-convulsive seizures, and number of spikes in the interictal period compared to those in the SD rat group. Power spectral analysis showed increased power in the delta band in both Wistar and SD rat groups. MRI, after CCA ligation, showed significantly lower ADC values, lower glutamine and glutamate levels, and higher lactate values in Wistar rats, although there was no difference in FA values. Metabolic and electrophysiological changes after CCA ligation differed according to the rat strain. Wistar rats were prone to increased lactate and decreased glutamine and glutamate levels and the development of status epilepticus. Seizures can affect the results of ischemic experiments.

Aging-associated inflammation and fibrosis in arachnoid membrane.

BACKGROUND: The physiological and pathological significance of the arachnoid membrane (AM) is still unknown. In this study, we investigated various characteristics of the AM, focusing on the influence of inflammation and fibrosis. METHODS: Small pieces of AM sample were obtained during neurosurgical procedures from 74 cases. The clinical and pathological characteristics of the hyperplastic AM group (≥ 50 µm) and the non-hyperplastic AM group (< 50 µm) were compared. Then, potential correlations between AM thickness and clinical characteristics were analyzed. Moreover, VEGFα, TGFß, and TGFα levels were quantitated by real time PCR. Then, the potential correlations between AM thickness and these inflammatory or anti-inflammatory markers, and the influence of the original disease were calculated. RESULTS: The median age of the patients in hyperplastic AM group was significantly older than that of the non-hyperplastic AM group. Moreover, the number of fibroblasts, CD68+ cells, CD86+ cells, and CD206+ cells in the hyperplastic AM group was significantly higher than that in the non-hyperplastic AM group. The AM thickness was significantly correlated to age and number of fibroblasts, CD68+ cells, CD86+ cells, and CD206+ cells. The thickness of the AM was significantly correlated to the messenger RNA expression levels of VEGFα (ρ = 0.337), and the VEGFα expression levels were significantly correlated with TGFß and TNFα. CONCLUSIONS: The AM hyperplasia was influenced by aging and could be a result of inflammation and fibrosis through cytokine secretion from the inflammatory cells and fibroblasts in the AM.