Published papers

A number of studies have reported the involvement of the ventral hippocampus (vHip) and the lateral septum (LS) in negative emotional responses. Besides these well-documented functions, they are also thought to control feeding behavior. In particular, optogenetic and pharmacogenetic interventions to LS-projecting vHip neurons have demonstrated that the vHip→LS neural circuit exerts an inhibition on feeding behavior. However, there have been no reports of vHip neuronal activity during feeding. Here, we focused on LS-projecting vCA1 neurons (vCA1→LS) and monitored their activity during feeding behaviors in mice. vCA1→LS neurons were retrogradely labeled with adeno-associated virus carrying a ratiometric Ca2+ indicator and measured compound Ca2+ dynamics by fiber photometry. We first examined vCA1→LS activity in random food-exploring behavior and found that vCA1→LS activation seemed to coincide with food intake; however, our ability to visually confirm this during freely moving behaviors was not sufficiently reliable. We next examined vCA1→LS activity in a goal-directed, food-seeking lever-press task which temporally divided the mouse state into preparatory, effort, and consummatory phases. We observed vCA1→LS activation in the postprandial period during the consummatory phase. Such timing- and pathway-specific activation was not observed from pan-vCA1 neurons. In contrast, reward omission eliminated this activity, indicating that vCA1→LS activation is contingent on the food reward. Sated mice pressed the lever significantly fewer times but still ate food; however, vCA1→LS neurons were not activated, suggesting that vCA1→LS neurons did not respond to habitual behavior. Combined, these results suggest that gastrointestinal interoception rather than food-intake motions or external sensations are likely to coincide with vCA1→LS activity. Accordingly, we propose that vCA1→LS neurons discriminate between matched or unmatched predictive bodily states in which incoming food will satisfy an appetite. We also demonstrate that vCA1→LS neurons are activated in aversive/anxious situations in an elevated plus maze and tail suspension test. Future behavioral tests utilizing anxious conflict and food intake may reconcile the multiple functions of vCA1→LS neurons.

Background/Aim: Many glioma patients struggle to return to work after surgery because of higher brain dysfunction. Although the right frontal lobe has historically been considered functionally silent, reports of performing awake surgery to evaluate higher brain functions in patients with tumors in this area have increased. We present two cases of patients who underwent awake surgery for malignant glioma in the right frontal lobe to preserve emotional recognition and facilitate an early return to work. Case Report: Case 1 was a 48-year-old right-handed woman employed as a nursery school teacher and case 2 was a 21-year-old right-handed man employed in sales. Both had contrast-enhancing right frontal lobe tumors exhibiting high signal intensity on fluid attenuated inversion recovery imaging and underwent awake surgery. During the operation, cortical mapping was performed using the Reading the Mind in the Eyes, calculation, and motor tasks. Resection of sites involved in motor and emotional recognition functions was avoided. In case 1, all regions of high signal intensity were completely resected; in case 2, all regions exhibiting enhancement were resected. Both patients were discharged home without neurological deficits and returned to work within 21 days after surgery. Conclusion: It may be important to focus not only on overall survival and progression-free survival in glioma patients, but also on factors associated with life satisfaction, such as time to return to work after surgery and time until work becomes difficult. Awake surgery aimed at preserving higher brain functions is useful and may also improve life satisfaction.

Epileptic encephalopathy with electrical status epilepticus during sleep (ESES) is often refractory to medical treatment and leads to poor cognitive outcomes. Corpus callosotomy may be an effective treatment option for drug-resistant ESES with no focal etiology. We retrospectively identified three patients who underwent corpus callosotomy for drug-resistant ESES in our institution. Electroencephalography (EEG) findings and cognitive functions were evaluated before surgery, at 3 months, 6 months, 1 year, and 2 years after surgery. Age at surgery was 6 years 10 months, 7 years 9 months, and 8 years 4 months, respectively. Period between the diagnosis of ESES and surgery ranged from 7 to 25 months. All patients had no obvious structural abnormalities and presented with cognitive decline despite multiple antiseizure medications and steroid therapies. One patient showed complete resolution of ESES and an improvement of intelligence quotient after surgery. Epileptiform EEG was lateralized to one hemisphere after surgery and spike wave index (SWI) was decreased with moderate improvement in development and seizures in the other 2 patients. SWI re-exacerbated from 6 months after surgery, but without subsequent developmental regression in these 2 patients. Corpus callosotomy may become an important treatment option for drug-resistant ESES in patients with no structural abnormalities.

Only few studies have assessed brain shift caused by positional change. This study aimed to identify factors correlated with a large postneurosurgical positional brain shift (PBS). Sixty-seven patients who underwent neurosurgical procedures had upright computed tomography (CT) scan using settings similar to those of conventional supine CT. The presence of a clinically significant PBS, defined as a brain shift of ≥ 5 mm caused by positional change, was evaluated. The clinical and radiological findings were investigated to identify factors associated with a larger PBS. As a result, twenty-one patients had a clinically significant PBS. The univariate analysis showed that supratentorial lesion location, intra-axial lesion type, craniectomy procedure, and residual intracranial air were the predictors of PBS. Based on the multivariate analysis, craniectomy procedure (p < 0.001) and residual intracranial air volume (p = 0.004) were the predictors of PBS. In a sub-analysis of post-craniectomy patients, PBS was larger in patients with supratentorial craniectomy site and parenchymal brain injury. A large craniectomy area and long interval from craniectomy were correlated with the extent of PBS. In conclusion, patients who undergo craniectomy and those with residual intracranial air can present with a large PBS. In post-craniectomy patients, the predisposing factors of a large PBS are supratentorial craniectomy, presence of parenchymal injury, large skull defect area, and long interval from craniectomy. These findings can contribute to safe mobilization among postneurosurgical patients and the risk assessment of sinking skin flap syndrome.

Objective: Postural changes influence systemic hemodynamics and may affect cerebral perfusion; however, quantitative evaluation remains limited in vivo under physiological gravitational conditions. We aimed to assess posture-dependent alterations in cerebral perfusion using upright multidetector computed tomography perfusion (CTP), with whole-brain cerebral blood flow (CBF) as the primary outcome. Materials and methods: This was a single-center observational study of healthy volunteers approved by the institutional review board. Eighteen volunteers underwent CTP imaging in both the supine and seated positions on the same day using two 320-row multidetector CT scanners with identical systems. Whole-brain CBF was defined as the primary endpoint. Mean transit time (MTT) and cerebral blood volume (CBV) were evaluated as secondary outcomes. Paired comparisons were performed between postures, and exploratory analyses assessed regional changes and interindividual variability. Results: Whole-brain CTP-derived CBF was significantly higher in the seated position than in the supine position (32.9 ± 6.0 [mean ± standard deviation] versus 29.2 ± 5.6 mL/100 g/min; p = 0.010), representing a 1.15 ± 0.19-fold increase. CTP-derived MTT was significantly shorter in the seated position (4.25 ± 0.61 versus 4.63 ± 0.72 s; p = 0.035), and CTP-derived CBV showed a modest but significant increase (2.23 ± 0.16 versus 2.16 ± 0.17 mL/100 g; p = 0.044). Regional perfusion changes were consistent across brain segments with interindividual variability in postural responses. Conclusions: Upright CTP detected posture-associated differences in whole-brain CTP-derived perfusion metrics, suggesting potential utility for investigating physiological and pathological alterations in cerebral hemodynamics associated with postural change. Relevance statement: Upright CTP enables physiological evaluation of posture-related cerebral hemodynamics under gravitational loading and may provide new insights into cerebral circulation in both health and disease. Key Points: Whole-brain cerebral blood flow increased by 15% in the seated position compared with supine using upright CT perfusion. Mean transit time shortened by 7% and cerebral blood volume increased modestly by 4% in the seated position. Perfusion responses showed marked interindividual variability, suggesting different physiological adaptations to posture.

We aimed to use upright computed tomography (CT) to depict posture-related changes in the brain tissue under normal gravity. Thirty-two asymptomatic volunteers underwent upright CT in the sitting position and conventional CT in the supine position on the same day. We compared the shift of the pineal body, cerebellar tonsil, the length of pituitary stalk, optic nerve sheath area and perimeter (ONSA and ONSP, respectively), and lateral ventricular volume between the supine and sitting positions. We also compared shape changes of the cerebrospinal fluid (CSF) spaces at different sites between both positions. In the sitting position, the pineal body shifted 0.68 ± 0.27 mm in the ventral direction and 0.76 ± 0.24 mm in the caudal direction, the length of pituitary stalk decreased by 1.23 ± 0.71 mm, the cerebellar tonsil descended by 2.10 ± 0.86 mm, the right ONSA decreased by 15.21 ± 6.54%, the left ONSA decreased by 15.30 ± 7.37%, the right ONSP decreased by 8.52 ± 3.91%, the left ONSP decreased by 8.20 ± 4.38%, and the lateral ventricular volume decreased by 5.07 ± 3.24% (all P < 0.001). We also observed changes in the shape of CSF spaces with changes in posture. We concluded that the intracranial structure of healthy subjects and volume of ventricles changed according to posture on Earth.

BACKGROUND AND OBJECTIVES: – Facial nerve preservation is critical in skull base surgery. Transcranial facial motor-evoked potential (tfMEP) monitoring can be limited by interindividual primary motor cortex (M1) facial cortex variability and intraoperative perturbations. We evaluated a functional MRI (fMRI)–guided, neuronavigation-assisted montage to personalize stimulating electrode placement and reduce thresholds during cerebellopontine angle tumor surgery.METHODS: – In a prospective cohort (n = 20), tfMEPs were recorded simultaneously using 2 montages: (1) fMRI-guided electrode directly over the patient-specific M1 facial hotspot identified by preoperative task fMRI and (2) conventional C3/C4. Train-of-five stimulation elicited compound muscle action potentials from orbicularis oculi/oris. The primary end point was stimulation threshold (mA) to elicit >50 µV, measured at predefined stages (precraniotomy through closure). Secondary analyses assessed threshold changes after durotomy/cerebrospinal fluid (CSF) drainage and postoperative House–Brackmann (HB) grades.RESULTS: – fMRI-guided placement yielded lower baseline thresholds than conventional within patients (mean 65.5 vs 73.5 mA; Δ = −8.9 mA; P < .0001). The advantage persisted at closure (85.3 vs 96.3 mA; P < .0001). After durotomy/CSF drainage, thresholds increased modestly with both montages (+3.3 vs +4.0 mA; between-group P = .65). Monitoring feasibility was 100%, providing continuous data early in the case when direct nerve stimulation was not yet possible. At the latest follow-up, 17/20 (85%) had HB I and 3/20 (15%) HB II; no patient had permanent moderate/severe palsy.CONCLUSION: – Neuronavigation-assisted, fMRI-guided tfMEP reliably targets the individual M1 facial area and significantly lowers stimulation thresholds vs conventional C3/C4, without increasing susceptibility to threshold drift after CSF loss. This simple, adoptable workflow may enhance intraoperative decision making for facial nerve preservation. Larger multicenter studies are warranted to validate outcome prediction and refine threshold-based alarm criteria.

Purpose: Few studies have investigated the influence of posture on the external jugular and diploic venous systems in the head and cranial region. In this study, we aimed to investigate the effects of posture on these systems using upright computed tomography (CT) scanning. Methods: This study retrospectively analysed an upright CT dataset from a previous prospective study. In each patient, the diameters of the vessels in three external jugular tributaries and four diploic veins were measured using CT digital subtraction venography in both supine and sitting positions. Results: Amongst the 20 cases in the original dataset, we eventually investigated 19 cases due to motion artifacts in 1 case. Compared with the supine position, most of the external jugular tributaries collapsed, and the average size significantly decreased in the sitting position (decreased by 22–49% on average). In contrast, most of the diploic veins, except the occipital diploic veins, tended to increase or remain unchanged (increased by 12–101% on average) in size in the sitting position compared with the supine position. However, the changes in the veins associated with this positional shift were not uniform; in approximately 5–30% of the cases, depending on each vein, an opposite trend was observed. Conclusion: Compared to the supine position, the contribution of external jugular tributaries to head venous drainage decreased in the sitting position, whilst most diploic veins maintained their contribution. These results could enhance our understanding of the physiology and pathophysiology of the head region in upright and sitting positions.

Background: Awake surgery with intraoperative language mapping has become increasingly refined, allowing assessment not only of motor but also higher brain functions. Language remains the most critical function to evaluate and preserve. However, reports of multilingual patients undergoing such procedures are still limited, particularly those involving Japanese, a linguistically and structurally unique language. Case description: We present the case of a 32-year-old right-handed multilingual male (Japanese L1, English L2, French L3), a film director and actor, who underwent awake craniotomy for a recurrent low-grade glioma involving the left temporal lobe. Preoperative functional MRI confirmed left hemispheric language dominance across all three languages, although French and English showed broader activation than Japanese during semantic fluency tasks. During surgery, cortical mapping with object naming and reading tasks was performed in Japanese, English, and French. Naming errors were observed in the posterior superior temporal gyrus across all three languages, whereas semantic paraphasia in the posterior middle temporal gyrus and reading impairment in the posterior inferior temporal gyrus were specific to Japanese. Postoperative MRI revealed subtotal resection with preservation of language function. Histopathology confirmed astrocytoma, IDH-mutant, WHO grade 3. Conclusion: This case represents the first report of intraoperative language mapping in a Japanese–English–French trilingual patient, demonstrating both overlapping and language-specific cortical regions. The findings underscore the importance of individualized and multimodal language mapping in multilingual patients, particularly when typologically distant languages such as Japanese are involved.

OBJECTIVE Hemispherotomy is an effective treatment for intractable hemispheric epilepsy; however, hydrocephalus remains a common complication of the procedure. The causes of hydrocephalus following hemispherotomy have not been fully elucidated; therefore, the purpose of this study was to identify the risk factors associated with the condition. METHODS The authors investigated the records of all patients aged < 18 years who underwent hemispherotomy at their institution between 2003 and 2020 and were monitored for hydrocephalus for at least 1 year after the procedure. To identify the risk factors for hydrocephalus, the following information about each patient was collected: sex, corrected age at surgery, body weight at surgery, previous intracranial surgery, etiology of epilepsy, results of PET for hypermetabolism, side of surgery, type of operation (vertical or horizontal approach), operation time, blood loss during surgery, use of intraventricular drainage, occurrence of intraventricular hemorrhage (IVH) on the 1st postoperative day, duration of postoperative fever of > 38°C, and maximum C-reactive protein level after the operation. Multivariate logistic regression analyses were performed. RESULTS This study included 51 children who underwent hemispherotomies for drug-resistant epilepsy at our hospital. Seven patients (13.7%) experienced hydrocephalus and were treated with ventricular or subdural peritoneal shunts or fenestration. Multivariate logistic analysis using the Bayesian information criterion revealed that 3 factors were associated with the occurrence of hydrocephalus: age at surgery, postoperative IVH volume, and duration of postoperative fever of > 38°C. CONCLUSIONS This study showed that younger age at surgery, postoperative IVH volume, and duration of postoperative fever of > 38°C might be risk factors for hydrocephalus after hemispherotomy. The risk of hydrocephalus should be considered in cases of early surgical indication in children. Intraoperative hemostasis and postoperative use of anti-inflammatory measures may reduce the risk of hydrocephalus.

Low-grade epilepsy-associated tumors (LEATs) are common in the temporal lobe and can cause drug-resistant epilepsy. Complete resection of LEATs is sufficient for seizure relief. However, hippocampal resection might result in postoperative cognitive impairment. This study aimed to clarify the necessity of hippocampal resection for seizure and cognitive outcomes in patients with temporal lobe LEATs and a normal hippocampus. The study included 32 patients with temporal lobe LEATs and without hippocampal abnormalities. All patients underwent gross total resection as treatment for drug-resistant epilepsy at our tertiary epilepsy center from 2005 to 2020, followed by at least a 12-month follow-up period. Seizure and cognitive outcomes were compared between patients who underwent additional hippocampal resection (Resected group) and those who did not (Preserved group). Among the participants, 14 underwent additional hippocampal resection and 28 (87.5%) achieved seizure freedom irrespective of hippocampal resection. The seizure-free periods were not different between the two groups. Additional hippocampal resection resulted in a significantly negative impact on the postoperative verbal index. In conclusion, additional hippocampal resection in patients with temporal lobe LEATs without hippocampal abnormalities is unnecessary because lesionectomy alone results in good seizure control. Additional hippocampal resection may instead adversely affect the postoperative language function.

Background: Patients with generalized epilepsy who had lateralized EEG abnormalities after corpus callosotomy (CC) occasionally undergo subsequent surgeries to control intractable epilepsy. Objectives: This study evaluated retrospectively the combination of EEG multiscale entropy (MSE) and FDG-PET for identifying lateralization of the epileptogenic zone after CC. Methods: This study included 14 patients with pharmacoresistant epilepsy who underwent curative epilepsy surgery after CC. Interictal scalp EEG and FDG-PET obtained after CC were investigated to determine (1) whether the MSE calculated from the EEG and FDG-PET findings was lateralized to the surgical side, and (2) whether the lateralization was associated with seizure outcomes. Results: Seizure reduction rate was higher in patients with lateralized findings to the surgical side than those without (MSE: p < 0.05, FDG-PET: p < 0.05, both: p < 0.01). Seizure free rate was higher in patients with lateralized findings in both MSE and FDG-PET than in those without (p < 0.05). Conclusions: This study demonstrated that patients with lateralization of MSE and FDG-PET to the surgical side had better seizure outcomes. The combination of MSE and conventional FDG-PET may help to select surgical candidates for additional surgery after CC with good postoperative seizure outcomes.

Perampanel (PER) is an antiseizure medication (ASM) with a unique mechanism of action, which was approved in Japan for use in combination therapy in 2016 and as a monotherapy in 2020. It has exerted antitumor effects against several types of tumors in vitro. However, the efficacy of PER monotherapy for seizure control is not well established in patients with brain tumor. In the present study, 25 patients with brain tumor treated using PER monotherapy at our institution were analyzed and compared with 45 patients treated using the most commonly prescribed ASM, levetiracetam (LEV). The PER group was younger and had a higher frequency of glioma cases. During drug administration, seizures were observed in two patients from the PER group (8.0%) and five patients from the LEV group (11.1%); however, the difference was not significant. The incidence of adverse effects did not significantly differ between the groups (12.0 and 2.2%, respectively). In the PER group, mild liver dysfunction was observed in two patients and drug rash in one. In the LEV group, a drug induced rash was observed in one patient. PER monotherapy may be safe and effective for seizure treatment or prophylaxis in patients with brain tumor. Further large scale clinical studies are warranted.

Background: Posterior fossa arachnoid cysts are often asymptomatic, but can rarely cause postural headache, the mechanism of which remains unknown. Case Description: We present a 40-year-old woman with an asymptomatic supracerebellar arachnoid cyst. Upright computed tomography (CT) showed enlargement of the arachnoid cyst and caudal descent of the cerebellum compared with supine CT with narrowing of the craniocervical junction cerebrospinal fluid space. Conclusions: This finding aids in understanding the association of posterior fossa arachnoid cysts with orthostatic headache. Clinicians should be aware of possible posture-related changes in intracranial structures.

Introduction Traumatic brain injury (TBI) often causes permanent neurological dysfunction. Although no medication has been validated yet to prevent secondary injury of brain tissue, recent animal studies have reported that perampanel, a glutamine receptor antagonist, could improve the neurological functions of animals with TBI by mitigating the abnormal calcium influx and cell death around the site of primary injury. The present study aims to elucidate the efficacy of perampanel administration in improving the neurological function of patients with TBI. Methods and analysis The perampanel for alleviation of secondary injury in TBI trial is a multicentre, phase-II, open-label randomised controlled trial targeting patients with mild-to-moderate TBI. This trial will include adult TBI patients with a Glasgow Coma Scale score of 9-14 from five tertiary centres. Patients with epilepsy as a comorbidity, delayed presentation of symptoms (>24 hours after injury) or Injury Severity Score of ≥25 will be excluded. The study participants will be randomly assigned to either the perampanel group (2 mg/day) or the control group (fosphenytoin administered at a dose of 15-18 mg/kg/day, followed by 5-7.5 mg/kg/day of fosphenytoin). In both groups, the medication will be initiated within 12 hours of the TBI diagnosis and continued for 7 days. The antiepileptic drugs can be increased, changed or added as necessary if early post-traumatic seizures are observed. The primary outcome is favourable neurological outcome, defined as a Glasgow Outcome Scale Extended score of ≥5 at 90 days after the TBI diagnosis, which will then be compared between the groups through an intention-to-treat analysis. Ethics and dissemination The present study has been approved by the Certified Review Board of Keio at the principal institution (approval number: N20240004). Written informed consent will be obtained from all participants or their legal representatives. The results will be disseminated via publications and presentations. Trial registration number Japan Registry of Clinical Trials (jRCTs031250067).

Considering that seizure freedom is one of the most important goals in the treatment of epilepsy, repeat epilepsy surgery could be considered for patients who continue to experience drug-resistant seizures after epilepsy surgery. However, the chance of seizure freedom is reported to be below 50% after reoperation for failed epilepsy surgery. This study aimed to elucidate the predictive factors for seizure outcomes after repeat pediatric epilepsy surgery. In all, 39 pediatric patients who underwent repeat curative epilepsy surgery between 2008 and 2020 at our institution were retrospectively studied. The relationship between preoperative clinical factors and postoperative seizure freedom at the last follow-up was statistically evaluated. The mean age at the first surgery was 5.5 years (0–16). The etiology of epilepsy was malformation of cortical development in 33 patients. The average time to seizure recurrence after the first surgery was 6.4 months (range, 0–26 months). In all, 16 patients (41.0%) achieved seizure freedom after the second surgery. Seven patients underwent a third surgery, and three (42.9%) achieved seizure freedom. Overall, 19 patients achieved seizure freedom after repeat epilepsy surgery (48.7%). Female sex, surgical failure due to technical limitations, congruent electroencephalography (EEG) findings, lesional magnetic resonance imaging (MRI) and Rt-sided surgery were predictive of seizure free-dom, and surgery limited to the temporal lobe was predictive of residual seizures, as determined in the multivariate analysis. The reoperation of failed epilepsy surgery is challenging. Consider-ation of the above predictive factors can be helpful in deciding whether to reoperate on pediatric patients whose initial surgical intervention failed.

BACKGROUND: Corpus callosotomy (CC) is a palliative neurosurgical procedure for patients with intractable epilepsy and without resectable focal epileptogenic lesions. Anterior commissurotomy (AC) has been historically performed with CC. However, the efficacy and safety of adding AC to CC remain unknown. OBJECTIVE: To describe the surgical technique of extraventricular AC and retrospectively investigate its clinical efficacy and safety by assessing patients who underwent CC with and without AC. METHODS: AC has been added to CC at our institution since 2018. Fifty-five consecutive patients who received total callosotomy from 2016 to 2020 were included and categorized into 2 groups: 26 patients with additional AC and 29 patients without additional AC. Seizure outcome 1 year after surgery were compared between groups for assessing the efficacy of adding AC. The perioperative factors were compared for assessing the safety and feasibility. RESULTS: Seizure reduction rate (50% and 60%; P = .60) and disappearance of drop attacks (42% and 58%; P = .25) were not significantly different between CC and CC + AC groups. No statistical group differences were found in intraoperative estimated blood loss, number of days to first oral intake, duration of postoperative intravenous hydration, and length of hospital stay. CONCLUSION: Disconnection of the anterior commissure is a feasible and relatively safe procedure. This study failed to show the significant efficacy of adding AC to CC. However, further investigation is needed to prove its efficacy in ameliorating epilepsy.

Implantation of subdural electrodes on the brain surface is still widely performed as one of the “gold standard methods” for the presurgical evaluation of epilepsy. Stereotactic insertion of depth electrodes to the brain can be added to detect brain activities in deep-seated lesions to which surface electrodes are insensitive. This study tried to clarify the efficacy and limitations of combined implantation of subdural and depth electrodes in intractable epilepsy patients. Fifty-three patients with drug-resistant epilepsy underwent combined implantation of subdural and depth electrodes for long-term intracranial electroencephalography (iEEG) before epilepsy surgery. The detectability of early ictal iEEG change (EIIC) were compared between the subdural and depth electrodes. We also examined clinical factors including resection of MRI lesion and EIIC with seizure freedom. Detectability of EIIC showed no significant difference between subdural and depth electrodes. How-ever, the additional depth electrode was useful for detecting EIIC from apparently deep locations, such as the insula and mesial temporal structures, but not in detecting EIIC in patients with ulegyria (glial scar). Total removal of MRI lesion was associated with seizure freedom. Depth electrodes should be carefully used after consideration of the suspected etiology to avoid injudicious usage.

BACKGROUND: Transsphenoidal endoscopic endonasal surgery (EES) provides effective treatment for patients with lesions of the sella turcica. The endoscopic technique requires different instrumentation, which depends on the gross anatomy of the nasal cavity. The treatment of lateral lesions is more challenging in EES. OBJECTIVE: To evaluate the effect of preoperative simulation using multiple anatomic landmarks. METHODS: Pre- and postoperative tumor volumes were analyzed in 33 patients with nonfunctioning pituitary adenomas who underwent EES (Knosp grades 3 and 4). The surgical working angle and space were three-dimensionally simulated at the plane of the anterior/posterior surgical field (tuberculum sellae/posterior clinoid process) using multiple anatomic landmarks of high-resolution computed tomography scans, such as nasal piriform aperture (proximal surgical corridor), and the width of bilateral vidian canals or lamina perpendicularis of palatine bone (distal surgical corridor). Receiver operating characteristic curves for the removed tumor volume were used to determine the cutoff value for the simulated working angle and space. RESULTS: Simulated working space at the plane of tuberculum sellae using piriform aperture and lamina perpendicularis of palatine bone was associated with the removed tumor volume in the cavernous sinus. Patients with a larger working space (≥42.7 mm) significantly showed a higher removed tumor volume (P = .023). There was no relationship between other parameters and the removed tumor volume. CONCLUSION: A new method to predict the surgical field for cavernous sinus lesions around sella turcica was successfully established. Further studies are needed to define and expand applications of this simulation method.

Fibrous dysplasia (FD), a developmental, nonfamilial, benign anomaly of bone development, is characterized by the replacement of normal bone by proliferating fibro-osseous tissue. Marked craniofacial deformities, functional disturbances, and emotional stress are major indications for treatment, and various surgical procedures have been performed; however, excision and regrowth issues have also been reported. While several treatment options are available, no studies have reported the natural history of untreated FD. Here, we report 2 patients, aged 73 and 50 years, respectively, who had not received treatment. Both patients presented to the hospital complaining of noise when moving their heads. Computed tomography scans showed niveau with honeycomb cavities in both patients, indicating abscess formation, and resection was performed. Relatively large cranial FD leads to the development of central necrosis over time. In such cases, surgical intervention should be performed at an early disease stage.