Background:Glioblastoma (GB), IDH-wildtype, and low-grade glioma appear indistinguishable in their early pre-symptomatic phase, yet GB follows a far more aggressive clinical course. While genomic studies suggest a "biological birth" of GB years before diagnosis, when GB first becomes radiologically detectable (radiological birth) remains unknown. Methods:We analyzed longitudinal imaging data from 67 early-stage glioblastoma (earlyGB) cases, characterized by small, asymptomatic lesions that later progressed to classic magnetic resonance imaging appearance of GB (classicGB), comprising 44 institutional and 23 from published reports. A mathematical model integrating tumor volume, radius, imaging intervals, clinical data, and molecular features estimated radiological birth and its modifiers. Results:The median interval from earlyGB to classicGB was 155 days (range: 35-1557) in our cohort and 113 days (range: 4-854) in the published cohort. Radiological birth occurred 0.83 years (95% CI: 0.66-1.10) before diagnosis in our cohort and 0.15-0.92 years in the published cohort. Rapid progression correlated with age <65 years, MIB1 labeling index ≥30%, and copy-number alterations (CNAs) in EGFR, PTEN, or CDKN2A, but not with TERT promoter status. Absence of these CNAs prolonged the radiological birth to 2.27 years (95% CI: 0.79-100), indicating slower progression. Median overall survival of our cohort was 1.7 years, yielding a radiological-birth-to-death span of 2.8 years. Conclusions:This largest earlyGB cohort defines the radiological birth and entire clinical trajectory of IDH-wildtype GB. These findings bridge the gap between biological and radiological birth and offer a benchmark for surveillance and early-intervention strategies.

Abstract BACKGROUND The management of infantile central nervous system germ cell tumors (CNS-GCTs) presents unique challenges, including variable clinical presentations such as tumor size and propensity for hemorrhage. Moreover, data on the clinical and molecular features remain limited. METHODS We conducted a clinical and molecular analysis of CNS-GCTs in children aged 6 years or younger, registered with the Japan Children’s Cancer Group and the iGCT consortium. DNA methylation analysis was performed using the Illumina Methylation EPIC array to identify potential molecular prognostic indicators. RESULTS The cohort comprised 43 patients, with a median age at onset of 6.5 months (0–68 months). Notably, 23 patients (54%) were diagnosed before 1 year of age. The male-female ratio was 27:15. Most common tumor location was cerebellum (13 cases). The median AFP level was 538 ng/ml (0–206460). Pathologically, the tumors were predominantly diagnosed as teratomas and yolk sac tumors. Teratomas were more common in patients diagnosed before 1 year of age, while mixed GCTs were more frequent in those diagnosed after 3 years. Molecular analysis identified four cases as embryonal tumors, including three AT/RTs and one DICER1-mutant intracranial sarcoma. The 3-year overall survival rates varied significantly by diagnosis: mixed GCTs at 100%, teratomas at 90.6%, yolk sac tumors at 30.0%, and embryonal tumors at 0%. Notably, two patients with teratomas developed metachronous tumors more than 10 years post-diagnosis, with both secondary tumors exhibiting mutations in the MAPK pathway absent in the primary tumors. CONCLUSION Infantile CNS-GCTs exhibit distinct clinical and molecular profiles compared to those in older children and adults. Not all tumors classified as GCTs based on molecular characterization were GCTs; some were embryonal tumors, potentially impacting treatment strategy. The genetic analysis suggests that some metachronous GCTs may represent second primary tumors rather than recurrences.

Central nervous system manifestations, a variety of benign and malignant tumors as well as non-neoplastic abnormalities, are found in over 70% of neurofibromatosis type 1 (NF1) patients. Herein, we report hitherto undescribed space-occupying lesions in the setting of NF1. We aimed to clarify their characteristics, especially whether they represent neoplastic or non-neoplastic (hyperplastic) lesions. All 3 cases were preoperatively assessed as non-neoplastic; 2 and 1 cases were suspected to be arachnoid cysts and dilation of subarachnoid space, respectively. However, all lesions were revealed to be whitish jelly-like masses by operation, and the histology composed of spindle cells resembling arachnoid trabecular cells with moderate cellularity and cellular uniformity gave an impression that these lesions may be neoplastic. In contrast, electron microscopic analysis showed that the characteristics of these cells were compatible with those of normal arachnoid trabecular cells. Furthermore, whole-exome sequencing and array comparative genomic hybridization did not show any obvious alterations suggestive of their neoplastic nature. DNA methylation analysis demonstrated that these lesions were epigenetically distinct not only from meningiomas but also from normal healthy meninges. In conclusion, considering the clinicopathologic aspects of the present lesions and the results of the molecular analysis that failed to suggest their neoplastic nature, they may represent previously unrecognized rare hyperplasia of arachnoid trabecular cells, which may be associated with NF1.

Central nervous system manifestations, a variety of benign and malignant tumors as well as non-neoplastic abnormalities, are found in over 70% of neurofibromatosis type 1 (NF1) patients. Herein, we report hitherto undescribed space-occupying lesions in the setting of NF1. We aimed to clarify their characteristics, especially whether they represent neoplastic or non-neoplastic (hyperplastic) lesions. All 3 cases were preoperatively assessed as non-neoplastic; 2 and 1 cases were suspected to be arachnoid cysts and dilation of subarachnoid space, respectively. However, all lesions were revealed to be whitish jelly-like masses by operation, and the histology composed of spindle cells resembling arachnoid trabecular cells with moderate cellularity and cellular uniformity gave an impression that these lesions may be neoplastic. In contrast, electron microscopic analysis showed that the characteristics of these cells were compatible with those of normal arachnoid trabecular cells. Furthermore, whole-exome sequencing and array comparative genomic hybridization did not show any obvious alterations suggestive of their neoplastic nature. DNA methylation analysis demonstrated that these lesions were epigenetically distinct not only from meningiomas but also from normal healthy meninges. In conclusion, considering the clinicopathologic aspects of the present lesions and the results of the molecular analysis that failed to suggest their neoplastic nature, they may represent previously unrecognized rare hyperplasia of arachnoid trabecular cells, which may be associated with NF1.

間脳下垂体腫瘍手術に必要な微小外科解剖, 病理と手術戦略について解説する. この手術に必要な微小外科解剖で最近注目されているのが上下垂体動脈 (superior hypophyseal artery : SHA) である. これは内頚動脈硬膜輪近傍の内側部から主幹として発生し, その後分枝するものが多く, 下垂体茎側では吻合形成するため血行障害が生じにくいが, 分枝後に視神経に向かう分枝は盲端となっており, 血行障害に弱いので注意を要する.

頚動脈高度狭窄症に対する頚動脈内膜剝離術（carotid endarterectomy：CEA）において，手術手技上の最大のポイントは内頚動脈遠位端のプラーク断端の処置であり，高位病変はプラーク遠位端確保を困難にする要因の1つである．頭蓋底外科領域における頚静脈孔神経鞘腫などでおもに使用される，頚静脈孔から内頚静脈を露出するhigh cervical approachの知識が有用である．今回，high cervical approachを行った際の解剖学的観点と実際の症例における手技を踏まえ，特別な操作を必要としないCEAにおける安全な到達限界を示す．加えて，実際の症例における遠位端到達限界での内シャント挿入困難時の対処法を報告する．結果，C1横突起のレベルで内頚静脈が視野を妨げ，下位脳神経が内頚動脈の前-外側面へ走行を変えるため，破裂孔からC1横突起までは内頚動脈の観察は難しく，C1横突起が到達点限界であると考える．そして，実際には内シャントを入れることを考えると，プラークの遠位端はC2椎体上縁が限界である．剝離限界の遠位内頚動脈において正常血管腔確保ができず内シャント挿入が困難な場合，遠位端プラークを先に剝離摘出することで内シャント挿入が容易になる．簡便で安全な方法である．

There has been a noted increase in the incidence of intracranial aspergillosis; this is often attributed to the wider use of antibiotics, corticosteroids, and immunosuppressants. Fungal cerebral aneurysms due to aspergillosis after neurosurgery remain extremely rare; in fact, only seven cases have been reported in the literature. In this study, we present a patient with an Aspergillus aneurysm that elicited subarachnoid hemorrhage after endoscopic endonasal surgery (EES) for craniopharyngioma. A 70-year-old woman with recurrent craniopharyngioma and steroid treatment underwent uneventful EES. On the 5th postoperative day, she suffered subarachnoid hemorrhage. As per her computed tomography angiography findings, an aneurysm was detected on the left internal carotid artery (ICA). Subsequent digital subtraction angiography showed occlusion of the ICA and an irregularly shaped wall. The diagnosis was pseudoaneurysm. We then performed craniotomy to place a left high-flow bypass and to trap the pseudoaneurysm. Despite continuous intensive care, she died on the 25th postoperative day of a huge, left cerebral infarct. The final diagnosis was made at autopsy; it revealed destruction of the ICA and Aspergillus invasion of the vessel wall, confirming the presence of a true fungal aneurysm. Perioperatively, patients with potential immunosuppression must be carefully managed. Advanced age is a risk factor. As surgery via the paranasal sinuses raises the risk for aspergillosis, fungal infection must be ruled out in patients whose postoperative course is deemed concerning.

Purpose: Anesthetic fade refers to the time-dependent decrease in the amplitude of the intraoperative motor-evoked potential. It is thought to be caused by the accumulation of propofol. The authors examined whether normalization by the compound muscle action potential (CMAP) after peripheral nerve stimulation could compensate for anesthetic fade. Methods: In 1,842 muscles in 578 surgeries, which did not exhibit a motor-neurologic change after the operation, the motor-evoked potential amplitude was normalized by the CMAP amplitude after peripheral nerve stimulation, and the CMAP amplitude and operation times were analyzed. Results: The amplitudes of both motor-evoked potential and CMAP increased over time after peripheral nerve stimulation because of the disappearance of muscle-relaxant action. Especially, after peripheral nerve stimulation, CMAP significantly increased from the beginning to the end of the operation. Anesthetic fade in transcranial motor-evoked potential monitoring seemed to occur at more than 235 minutes of surgery based on the results of a receiver operating characteristic analysis of the operation time and relative amplitudes. Although the mean amplitude without CMAP normalization at more than 235 minutes was significantly lower than that at less than 235 minutes, the mean amplitude with normalization by CMAP after peripheral nerve stimulation at more than 235 minutes was not significantly different from that at less than 235 minutes. Conclusions: Compound muscle action potential after peripheral nerve stimulation normalization was able to avoid the effect of anesthetic fade. Anesthetic fade was seemed to be caused by a decrease in synaptic transmission at the neuromuscular junction because of propofol accumulation by this result.

Background : We normalized the amplitude of motor-evoked potential (MEP) monitoring using compound muscle action potential (CMAP) generated by peripheral nerve stimulation. Anesthetic fade refers to a time-dependent decrease in the amplitude of intraoperative MEP. It is thought to result from the accumulation of propofol. We examined whether normalization by CMAP after peripheral nerve stimulation could increase the sensitivity and specificity of MEP monitoring and compensate for anesthetic fade during spinal surgery.

Abstract AT/RT is a malignant embryonal tumor reported by Rorke in 1996. Authors reported first AT/RT in Japan in 1998. This tumor entity was included as new malignant embryonal tumor in WHO 2000, and tumors of Japanese patients has been reported more than 80 cases in the past. This AT/RT is a tumor in the brain parenchyma that a medulloblastoma and PNET and the possibility that it has been misdiagnosed have had pointed out. On the other hand, it is reported that there is the type that we should call peripheral AT/RT which rarely occurs in extra-parenchyma. We want to propose that there is such special tumor group. In the results, age: 17 infants were main (2nd - 14 years old after birth). tumor location: 22 sellar or parasellar regions, 8 CP angles, 7 oculomoter nerves, and 3 petrous bone, treatment: duration of survival significantly improved all macroscopic tumor resection by the operation, but, in small pontine part AT/RT, an outcome tended to be poor. On the other hand, in AT/RT which occurred in the sellar region, all cases adult woman tended to have good prognosis. It is necessary for AT/RT (central AT/RT) in the brain to recognize that there is extra-parenchymal AT/RT (peripheral AT/RT) tumor which we reported this time which came to be recognized widely.

INTRODUCTION:We present a patient with idiopathic spinal cord herniation (ISCH) whose dura mater was histopathologically examined to elucidate its pathogenesis.CASE REPORT:A 33-year-old previously healthy man presented with progressive walking difficulty, spasticity of the right lower leg, and hyperesthesia below the right chest. Neuroimaging revealed right ventral displacement of the spinal cord at T5-6. The diagnosis was ISCH and he underwent release of the herniation from the ventral dural opening. Dural biopsy at the edge of the ventral opening and in the dorsal durotomy was performed. Postoperatively, his gait was improved. Histopathological examination of the ventral dural specimen showed non-specific degeneration, i.e., loose arrangements of collagen fibers, edematous changes, minor inflammatory cell infiltration, and angiogenesis. The specimen from the dorsal durotomy was normal.CONCLUSION:It is unclear whether the observed degeneration besides the ventral opening was the primary cause of ISCH or reflected secondary changes resulting from cumulative damage due to pulsation of the herniated spinal cord. However, the degeneration limited to the ventral opening suggests that ISCH was a local event in an individual with a normal dural theca.

Abstract AT/RT is a malignant embryonal tumor reported by Rorke in 1996. Authors reported first AT/RT in Japan in 1998. This tumor entity was included as new malignant embryonal tumor in WHO 2000, and tumors of Japanese patients has been reported more than 60 cases in the past. This AT/RT is a tumor in the brain parenchyma that a medulloblastoma and PNET and the possibility that it has been misdiagnosed have had pointed out. On the other hand, it is reported that there is the type that we should call peripheral AT/RT which rarely occurs in extra-parenchyma. We want to propose that there is such special tumor group. In the results, age: 6 infants were main (2nd - 14 years old after birth). tumor location: 6 sellar region, 3 civuses, 2 petrous bone or cerebellum and 2 conexities. treatment: duration of survival significantly improved all macroscopic tumor resection by the operation, but, in small pontine part AT/RT, an outcome tended to be poor. On the other hand, in AT/RT which occurred in the sellar region, all cases adult woman tended to have good prognosis. It is necessary for AT/RT (central AT/RT) in the brain to recognize that there is extra-parenchymal AT/RT (peripheral AT/RT) tumor which we reported this time which came to be recognized widely.

A 43-year-old man fell from a 1m-high truck loading platform and sustained an injury in the occiput. On admission, he was alert and neurologically intact. Computed tomography(CT)showed hemorrhage in the right sylvian fissure and parenchyma adjacent to the sphenoid wing. Magnetic resonance angiography detected no abnormalities. The course was uneventful for 11 days. However, on the 12th day, he spontaneously manifested with stupor. CT and CT angiography revealed expansion of the hemorrhage and an aneurysm arising from the origin of the M2 segment of the right middle cerebral artery. After superficial temporal artery to middle cerebral artery bypass, the aneurysm, a reddish pulsatile mass, was removed from the origin of the torn M2 segment, and the laceration was sutured. The histological diagnosis was false aneurysm. He recovered and was discharged 4 months after the trauma. Traumatic cerebral aneurysms are rare in the proximal segment of the middle cerebral artery. However, they should be distinguished from nontraumatic true aneurysms in the same region and treated as false aneurysms, which are major and critical traumatic aneurysms, for favorable outcomes.

This 64-year-old woman had undergone endoscopic carpal tunnel release(ECTR)for right carpal tunnel syndrome 16 months earlier. Thereafter, she reported persistent dysesthesia in the thumb and index finger, developed burning pain in the middle and ring finger, paleness, coldness, and edema of the hand, a decreased range in hand motion, and a painful subcutaneous nodule just distal to the portal in the forearm. Based on physical, radiological, and electrophysiological studies, the diagnosis was incomplete carpal tunnel release associated with complex regional pain syndrome(CRPS). At open revision surgery, the carpal tunnel was released completely and the nodule was removed. Symptoms other than hypesthesia in the middle and ring fingers improved. Pathologically, the nodule was an amputation neuroma. Her CRPS was attributed to ECTR complications; i.e., persistence of median nerve compression and the formation of an amputation neuroma in the palmar cutaneous branch of the ulnar nerve at the portal. Surgeons must be aware that ECTR, a less invasive technique, may result in serious complications including CRPS.

Background: Distal Posterior Inferior Cerebellar (PICA) aneurysms are quite rare.The infrequency of distal PICA aneurysms has limited our understanding of their underlying pathology, natural history, and clinical management.Moreover, vascular anomalies are frequently noted in association with distal PICA aneurysms. Case Description:We present a very unique case of a ruptured distal PICA aneurysm associated with an Arteriovenous Malformation (AVM) which was successfully identified by Intraoperative Indocyanin Green (ICG) video angiography.In the current era, we tend to perform Computed Tomographic Angiography (CTA) studies as the initial imaging for vascular lesions.CTA revealed the distal PICA aneurysm but failed to reveal the associated AVM.However, intraoperative ICG video angiography strongly suspected the existence of an AVM. Conclusion:Intraoperative ICG video angiography is very useful in detecting small vessel anomalies.DSA should be considered for all distal PICA aneurysms even in the era of advanced CTA.

BACKGROUND: Recent genetic analysis of primary central nervous system lymphoma (PCNSL) showed that the MyD88 1265P mutation, which is related to NF-kappa B signaling, was a genetic hallmark for PCNSL; thus it could serve as a genetic marker for diagnosis and a potential target for molecular therapy. However, the role of the MyD88 mutation in PCNSL has not been defined. In this study, we investigated the role of the MyD88 mutation and clinical features of PCNSL-treated patients at several institutions to determine its significance as a prognostic factor. METHODS: Forty-one PCNSL (diffuse large B-cell type) patients from 8 institutions were included in this study. Their median age was 68 years; median follow-up was 26.7 months; median overall survival was 26.7 months; and their 1-year, 3-year, and 5-year survival rates were 75.6%, 58.5%, and 43.9%, respectively. Deoxyribonucleic acid was extracted from frozen tissue, and the MyD88 L265P mutation was evaluated by polymerase chain reaction and direct sequencing. RESULTS: The MyD88 L265P mutation was found in 61.0% (25/41) of cases. Kaplan-Meier analysis revealed that neither MyD88 L265P mutation nor age >65 years alone significantly predicted overall survival relative to MyD88 wild type and age <65. The MyD88 L265P mutation was predominantly present in patients aged >65 years. Among age >65 patients, the MyD88 L265P mutation portended a worse overall survival compared with the MyD88 wild type (11.5 vs. 56.2 months P < 0.04). CONCLUSION: The MyD88 L265P mutation predicted a poor prognosis in elderly PCNSL patients. A new tailormade treatment strategy might be needed for these patients.

BACKGROUND:Although intraoperative motor-evoked potential (MEP) monitoring is widely performed during neurosurgical operations, evaluating its results is controversial.STUDY AIMS:The cutoff point of MEP monitoring should be determined not only to predict but also to prevent postoperative neurologic deficits.MATERIAL AND METHODS:MEP monitoring was performed during 484 neurosurgical operations for patients without definitive preoperative motor palsy including 325 spinal operations, 102 cerebral aneurysmal operations, and 57 brain tumor operations, all monitored by transcranial stimulation, and 34 brain tumor operations monitored under direct cortical stimulation. To exclude the effects of muscle relaxants on MEP, the compound muscle action potential (CMAP), measured immediately after transcranial stimulation or direct cortical stimulation at supramaximal stimulation of the peripheral nerve, was used for normalization. The cutoff points, sensitivity, and specificity of MEP recorded during neurosurgery were examined by receiver operating characteristic (ROC) analyses and categorized according to the type of operation and stimulation.RESULTS:In spinal operations under transcranial stimulation, amplitude reduction of 77.9% and 80.6% as cutoff points for motor palsy with and without CMAP normalization, respectively, provided a sensitivity of 100% and specificity of 96.8% and 96.5%. In aneurysmal operations under transcranial stimulation, cutoff points of 70.7% and 69.6% offered specificities of 95.2% and 95.7% with and without CMAP normalization, respectively. The sensitivities for both were 100%. In brain tumor operations under direct stimulation, cutoff points were 83.5% and 86.3% with or without CMAP normalization, respectively, and the sensitivity and specificity for both were 100%.CONCLUSION:An amplitude decrease of 80% in brain tumor operations, 75% in spinal operations, and 70% in aneurysmal operations should be used as the cutoff points.