Pituitary neuroendocrine tumors (PitNETs) are generally benign; however, functional subtypes cause hormone hypersecretion, leading to systemic complications. In somatotroph PitNETs, growth hormone (GH) excess increases mortality and necessitates complete tumor resection to achieve endocrinological remission. Although extracapsular resection along the pseudocapsule is preferred, the plane may be poorly defined with tumor cells infiltrating adjacent normal tissue, necessitating further resection of the outer layer. Conversely, excessive resection increases the risk of postoperative hypopituitarism; therefore, precise intraoperative delineation of tumor boundaries is essential. Approximately half of the somatotroph PitNETs harbor GNAS mutations. We used a microfluidic real-time PCR platform (GeneSoC®) that detects mutations within approximately 15 min for intraoperative molecular boundary diagnosis. First, archival frozen samples were analyzed using Sanger sequencing, which identified GNAS R201C mutations in 11 of 24 samples (45.8

Although rare, thrombosed vertebral artery aneurysms can lead to severe symptoms and are challenging to treat due to their proximity to vital structures. The location of a thrombosed aneurysm on the anterior aspect of the brainstem poses a significant challenge to conventional microscopic approaches. We herein report a 78-year-old man with a thrombosed right vertebral artery aneurysm who developed progressive quadriparesis, dysphagia, and respiratory failure despite prior interventions, including flow diverter stent placement, parent artery occlusion, and microscopic thrombectomy. Given worsening medullary compression and poor clinical status, intra-aneurysmal thrombectomy was performed using an exo-endoscopic 2-step approach. The procedure involved reopening the previous suboccipital craniotomy, partial condylectomy, and C1 hemilaminectomy. Exoscopic thrombus de-bulking was followed by endoscopic evacuation of the residual thrombus compressing the ventral brainstem. Postoperatively, no complication was observed, and the patient demonstrated gradual neurological improvement, including recovery of spontaneous respiration and the ability to wean from mechanical ventilation within 3 weeks. Follow-up imaging confirmed resolution of medullary compression without thrombus recurrence. The exo-endoscopic 2-step approach is a viable option for surgical decompression of thrombosed vertebral artery aneurysms that cause brainstem compression. This enhances surgical access and visualization, particularly in the ventral brainstem, while potentially minimizing brainstem manipulation. Further investigation is warranted to better define the indications, efficacy, and safety of the management of complex thrombosed aneurysms.

ContextPituitary carcinoma is a rare and highly aggressive tumor. While anti-programmed cell death-1 (PD-1) therapy has shown efficacy in some cases, the factors that predict a favorable response remain largely unclear.ObjectiveTo evaluate tumor-infiltrating lymphocytes (TILs) in pituitary carcinoma and to compare T−cell receptor (TCR) clonotypes between the pituitary and peripheral blood.MethodsA 34-year-old woman with Lynch syndrome and adrenocorticotropic hormone-secreting pituitary carcinoma with hepatic metastasis received anti-PD-1 therapy, achieving durable disease control exceeding 1 year. Immunohistochemistry was performed on treatment-naïve surgical tumor samples, and TCR repertoire analyses were conducted on both the tumor sample and peripheral blood mononuclear cells collected during effective anti-PD−1 therapy.ResultsTreatment-naïve pituitary carcinoma tissues exhibited infiltration of CD4+ and CD8+ T cells. Analysis of the TCR repertoire identified 15 clonotypes with a high frequency (> 1% of sequencing reads) in the tumor; among these, four of the five most prevalent clonotypes were co-detected as dominant clones in peripheral blood after treatment, including the most abundant clones found within the CD4+ and CD8+ T cell populations. Despite control of the primary and hepatic lesions, ovarian metastasis developed, which was associated with reduced CD4+ TILs.ConclusionsThe presence of CD4+ and CD8+ TILs may underlie the immunological foundation for PD-1 blockade efficacy in pituitary carcinoma, supported by the detection of tumor-resident TCR clonotypes in peripheral blood during a positive therapeutic response.

BACKGROUND:Pituicytoma is a rare thyroid transcription factor-1 (TTF-1)-positive glial neoplasm classified as a posterior pituitary tumor in the 2022 WHO classification. Most cases arise in the sellar or suprasellar region; intraventricular occurrence is exceedingly rare, with only 6 cases reported in the literature. OBSERVATIONS:A 72-year-old man presented with an incidentally detected suprasellar mass that gradually enlarged over 18 months, resulting in visual field disturbance. Preoperative imaging demonstrated a well-enhancing lesion without calcification and with intratumoral flow voids suggestive of hypervascularity. The patient underwent extended endoscopic transsphenoidal surgery (eTSS). Intraoperatively, the tumor was located in the third ventricle without continuity with the pituitary gland or stalk. Subtotal resection was performed. Histopathological and immunohistochemical analyses demonstrated positivity for TTF-1, S100, and glial fibrillary acidic protein, and DNA methylation profiling confirmed the diagnosis of pituicytoma. At 6 months postoperatively, the residual tumor showed progression and was treated with Gamma Knife radiosurgery. LESSONS:This case suggests that pituicytoma may rarely originate from the floor of the third ventricle. Extended eTSS may represent a safe and minimally invasive surgical approach for selected third ventricular lesions. https://thejns.org/doi/10.3171/CASE26414.

BACKGROUND:Corticotroph pituitary neuroendocrine tumors (PitNETs) causing Cushing's disease require complete surgical resection to achieve endocrinological remission. Although endoscopic transsphenoidal surgery is the standard first-line treatment, accurate intraoperative delineation of tumor boundaries remains challenging because the pseudocapsule is often thin or ill-defined and tumor cells may infiltrate adjacent tissues. Given that intraoperative histopathology and conventional molecular methods are limited by time constraints, rapid molecular detection of tumor-specific mutations may serve as an intraoperative surrogate marker for tumor cell presence. NEW METHOD:We employed a microfluidic real-time PCR platform (GeneSoC®) capable of detecting mutations within a short timeframe for intraoperative molecular boundary diagnosis of corticotroph PitNETs. RESULTS:Sanger sequencing of archival frozen samples identified the USP8 P720R mutation, which was used to validate the real-time PCR assay. Using a fluorescence intensity cutoff value of 20, real-time PCR reliably discriminated mutation-positive from mutation-negative samples and detected mutations at variant allele frequencies of ≥ 2%. Intraoperatively, four samples obtained from different anatomical sites were analyzed, and real-time PCR detected the USP8 P720R mutation in all samples. COMPARISON WITH EXISTING METHODS:Real-time PCR rapidly provided diagnostic accuracy comparable to that of immunohistochemistry, Sanger sequencing, and droplet digital PCR. In one sample, the real-time PCR result was discordant with the hematoxylin and eosin staining findings. CONCLUSIONS:Real-time PCR may serve as a rapid and objective method for intraoperative molecular boundary assessment of corticotroph PitNETs, although further validation is required. This method could potentially be extended to other tumors harboring detectable genetic mutations.

Abstract Objective To evaluate clinical outcomes of pediatric cases with diffuse intrinsic pontine glioma (DIPG) treated at our institution and to analyze significance of endoscopic third ventriculostomy (ETV) in patients who developed hydrocephalus during clinical course. Background DIPG is a highly aggressive pediatric brain tumor with extremely poor prognosis. Previous studies reported that 15–60% of DIPG patients exhibit hydrocephalus within approximately 5 months after diagnosis, often further compromising quality of life. We aggressively perform endoscopic ETV for DIPG cases exhibiting suspected obstructive hydrocephalus based on MRI images. Methods We retrospectively reviewed the medical records of 27 consecutive pediatric patients with DIPG treated at our institution between January 2010 and December 2025. Demographic and clinical data, imaging findings, treatment details (including radiotherapy, biopsy, and CSF diversion), and outcomes were analyzed. Results The median age at diagnosis was 6 years (range, 2–13 years), and 8 patients (30%) were male. Stereotactic biopsy was performed in 3 patients (11%). All patients received initial radiotherapy with a planned dose of 54 Gy in 30 fractions, which was discontinued in 1 patient due to intratumoral hemorrhage. The median progression-free survival and overall survival were 5.6 and 11.7 months, respectively. Ventricular enlargement was found in 17 patients (68%) during the clinical course. Among them, we performed endoscopic ETV for 9 patients who developed symptoms associated with acute increasement of intracranial pressure (headache and vomiting in 6, impaired consciousness in 3) without significant ETV-related complications. All 9 patients showed rapid postoperative improvement of symptom. Among these 9 patients, for 6 patients (67%), ETV was performed within 3 months after initial diagnosis. No patients required subsequent permanent shunt placement. The median overall survival after ETV was 6.9 months. Conclusions The prognosis of DIPG remains dismal in the modern treatment era. For patients who developed ventricular enlargement at an early phase, ETV might be a safe and effective option for preservation of favorable quality of life during the remaining clinical course by preventing critical intracranial hypertension.

BACKGROUND:Endoscopic neurosurgery enables minimally invasive access to deep-seated lesions. However, surgical manipulation is restricted by the limited maneuverability of straight instruments within narrow corridors. To address these limitations, we developed a clinically applicable articulating dissector that enables multidirectional distal-tip motion without requiring shaft movement. METHODS:The dissector features a pistol-grip handle, a 130-mm shaft, and a distal tip capable of ± 45° articulation, with a 6-mm distance from the articulation joint to the tip to optimize stability. The device remained straight during insertion, allowing smooth advancement through narrow passages. We named the instrument the Patapata Dissector, using the Japanese mimetic word "patapata", which expresses the flapping motion of a bird's wings. Clinical feasibility and safety were evaluated in 20 consecutive cases: 10 endoscopic transsphenoidal surgeries and 10 endoscopic cylinder surgeries. RESULTS:The dissector allowed unimpeded insertion without interference from nasal structures, cylinder walls, or endoscopic equipment. During dissection, the articulating tip enabled precise multidirectional movement in deep operative fields, minimizing unintended force transmission and reducing collisions between instruments. In endoscopic transsphenoidal surgery, delicate separation of lesions from the pituitary stalk and lateral margins was achieved with minimal interference. In endoscopic cylinder surgery, the articulating tip facilitated horizontal and contralateral-side dissection beyond the cylinder boundaries. No device-related complications occurred. CONCLUSIONS:This newly developed articulating dissector expands the operable range and improves maneuverability in endoscopic neurosurgery by enabling controlled distal tip motion without the need for shaft manipulation. It represents a practical advancement in minimally invasive neurosurgical instrumentation.

Fourth ventricular arachnoid cysts are rare and optimal surgical management remains unclear. We describe a flexible endoscopic trans-third ventricular technique for the treatment of fourth ventricular arachnoid cysts associated with obstructive hydrocephalus. Through a frontal approach, a flexible neuroendoscope is advanced via the foramen of Monro and third ventricle into the dilated cerebral aqueduct, allowing access to the fourth ventricle. Cyst fenestration is performed using biopsy forceps and a balloon catheter, and communication with surrounding cerebrospinal fluid spaces can be established. Endoscopic third ventriculostomy is performed concomitantly to ensure cerebrospinal fluid diversion. In selected cases, additional caudal fenestration toward the cisterna magna can be achieved to enhance cerebrospinal fluid circulation. This minimally invasive technique avoids posterior fossa craniotomy and enables simultaneous treatment of hydrocephalus. The approach is particularly suitable for cases with sufficient aqueductal dilation and offers a safe and effective alternative in selected patients.

CONTEXT:Acromegaly poses clinical challenges in terms of early diagnosis and intervention. Therefore, the development of novel diagnostic tools is essential. Although artificial intelligence (AI) models based on external appearance have been proposed, privacy concerns have limited their use. OBJECTIVE:To develop a privacy-conscious deep learning model for detecting acromegaly using hand images. METHODS:This nationwide multicenter study enrolled 716 patients (317 with acromegaly and 399 controls) and 11 480 images from 15 Japanese pituitary centers. The inclusion criteria were age ≥18 years and care received at the participating facilities. Hand images focusing on the dorsal and fist sign, excluding the palm/fingerprint regions, were used to develop the model. The data were split into training/validation (12 centers) and test (3 centers) datasets. A ResNet-50-based model was trained using PyTorch with data augmentation and 5-fold cross-validation. For each patient, the predictions were averaged over 4 images. The performance of the model was compared with that of endocrinologists. RESULTS:The model achieved a sensitivity of 0.89, specificity of 0.91, positive predictive value of 0.88, negative predictive value of 0.93, F1-score of 0.89, and an area under the receiver operating characteristic curve of 0.96, outperforming specialists (F1-score range: 0.43-0.63). CONCLUSION:This study highlights the utility of dorsal hand and fist sign as diagnostic clues for acromegaly, which the AI model captured more accurately than endocrinologists. Using this privacy-conscious feature, this model can be deployed in public settings like health checkups. Further validation using larger datasets, including healthy individuals and diverse diseases, is necessary.

Surgical interventions for arachnoid cysts and glioependymal cysts primarily focus on cyst decompression and establishing communication with cerebrospinal fluid spaces. However, a standardized surgical strategy for symptomatic convexity cysts lacking surrounding cerebrospinal fluid space is still lacking due to the limited number of cases. This systematic review aims to evaluate surgical interventions for symptomatic convexity cysts and proposes a safe and effective treatment approach we have developed. A systematic review of the literature was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Surgical techniques were categorized into cystoperitoneal shunt, cyst excision, cyst fenestration, cyst ventriculostomy, and several uniquely modified methods. Using a method different from these previous reports, we performed endoscopic cystoventricular stenting via burr hole in 3 cases of convexity cysts. While traditional methods have proven effective, cystoperitoneal shunt may lead to malfunction, infection, and subdural hematoma; wall excision is invasive and increases morbidity risks. Fenestration and cystoventriculostomy have also reported cases of recurrence. Other methods also pose issues, including off-label use of instruments and inadequate consideration for removal. The method we performed for placing the stent catheter with multiple side holes demonstrated long-term effectiveness. Furthermore, the surgery was conducted with the patient fully awake, and the use of electrical stimulation mapping enabled preservation of higher neurocognitive functions, including language, working memory, and spatial cognition, at the puncture site. This novel approach offers advantages such as minimally invasive procedure, preservation of safe brain function, and long-term patency. Further studies are warranted to validate these findings and improve surgical strategies for convexity cysts.

Postoperative hematoma formation is one of the most life-threatening complications associated with giant pituitary adenomas, and various surgical methods have been proposed to mitigate this risk. This study aims to report our surgical outcomes in patients with giant pituitary adenomas and to identify risk factors associated with postoperative hematoma formation. We retrospectively reviewed 45 patients with giant pituitary adenomas who underwent surgical treatment. The surgical approaches included conventional transsphenoidal surgery in 24 patients, extended transsphenoidal surgery in 9, and simultaneous combined transsphenoidal surgery and transcranial surgery in 12. Intracapsular resection was performed in 28 patients, while extracapsular resection was carried out in 17 patients. Postoperative hematoma formation was observed in 17 patients; among them, 2 experienced neurological deterioration and subsequently required reoperation for hematoma evacuation. The mean maximum tumor diameter was significantly larger in patients with postoperative hematoma (54 mm) compared to those without (45.3 mm) (p = 0.008). Other tumor characteristics were not significantly associated with postoperative hematoma formation. Combined transsphenoidal surgery and transcranial surgery were more frequently performed in patients who developed postoperative hematoma (p = 0.007), whereas extracapsular resection was more common in those without hematoma (p = 0.001). However, these differences in postoperative hemorrhage incidence among surgical techniques may have been substantially influenced by selection bias. Giant pituitary adenomas with extensive intracranial extension and involvement of critical neurovascular structures remain challenging to manage regardless of the surgical approach. Nevertheless, it is essential to tailor surgical strategies to individual cases to minimize postoperative complications.

BACKGROUND:The 5th edition of the World Health Organization Classification of Tumors of the CNS introduced a subclassification of tumors based on key molecular markers. In adult-type diffuse gliomas, isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase (TERT) promoter mutations play pivotal roles in the molecular classification. This study developed a rapid genotyping system using GeneSoC, a real-time PCR platform with microfluidic thermal cycling capable of completing 50 cycles of PCR within 20 min. METHODS:To establish optimal analytical conditions, frozen tumor tissues from 67 patients and artificial DNA vectors were analyzed using this system. This system demonstrated a detection limit of at least 5% variant allele frequency for the IDH1 R132H and TERT promoter C228T/C250T mutations. Subsequently, intraoperative testing was performed in 120 cases using this system. RESULTS:The sensitivity and specificity of IDH1 R132H mutation were 0.985 and 0.982, respectively, whereas those of TERT promoter C228T/C250T mutation were 1.000 and 1.000, respectively. These mutations were detected intraoperatively within approximately 25 min after tumor tissue collection. Furthermore, this assay identified tumor boundaries in an IDH-mutated glioma case, where IDH1 R132H mutations could not be detected. CONCLUSIONS:The GeneSoC®︎-based rapid genotyping system may be effective not only for intraoperative diagnosis of diffuse glioma but also for detecting tumor boundaries.

Intraoperative magnetic resonance imaging (iMRI) plays a crucial role in improving the precision of brain tumor surgeries. However, the use of iMRI can impose certain limitations on intraoperative head positioning. In regular microscopic surgery, head positioning is of utmost importance because an appropriate surgical field is important for the efficacy and safety of surgery. Therefore, in cases where adequate head positioning is difficult, usually, iMRI will not be utilized. Herein, we report an adult case of cerebellar astrocytoma whose tumor extended to the culmen of the cerebellum. Upon surgery via the suboccipital approach, the positional limitations imposed by iMRI led to an insufficient vertex-down position and limited surgical field, which hampered the removal of the upper portion of the tumor. However, this concern could be overcome when used in combination with an endoscope. The potential of iMRI applications is anticipated to be enhanced by overcoming positional limitations through combined endoscopic surgery. The use of multimodality in surgery is an optimal example of how surgical support equipment can also improve surgical outcomes. Here, we report on the new possibilities offered by multimodality.

PURPOSE:This study aimed to evaluate the efficacy and safety of intravenous perampanel (IV-PER) in routine clinical practice. METHODS:Patients who received IV-PER at Nagoya University Hospital or one of the 21 affiliated institutions between June 2024 and March 2025 were included. Indications for IV-PER included treatment for epileptic seizures, particularly acute symptomatic seizures, and prophylactic use before or after surgery. The primary endpoint was the seizure suppression rate within 7 days of treatment initiation, and the secondary endpoint was the incidence of adverse events (AEs). Clinical data were recorded daily, and blood tests were conducted within 2 weeks of administration. Enrolled patients were categorized into three groups based on the underlying etiology: cerebrovascular disease (CD), brain tumor (BT), and traumatic brain injury (TBI). Treatment efficacy and safety were assessed across these groups. RESULTS:Of the 237 patients, 74, 116, and 47 were classified into the CD, BT, and TBI groups, respectively. The overall seizure suppression rate within 7 days was 89.0 %. Rates by group were 87.8 % (CD), 96.6 % (BT), and 72.3 % (TBI). When stratified by indication, the rates were 99.3 % for prophylactic use, 69.4 % for focal seizures, and 74.4 % for generalized seizures. Regarding AEs, somnolence was reported in 3 patients and irritability in one. Laboratory abnormalities included anemia, elevated liver enzymes, elevated creatine kinase, and hyponatremia. A total of 71 patients experienced one of these. CONCLUSIONS:This large multicenter prospective registry demonstrates that IV-PER can be safely used for seizure management during the 7-day acute phase in real-world clinical settings.

Intracanalicular residual vestibular schwannoma (VS) after surgical resection is known to cause recurrence. Lesions demonstrating progression despite adjuvant stereotactic radiosurgery necessitate salvage surgery with meticulous tumour resection to prevent recurrence. We describe our exo- and endoscopic two-step approach (EETA), employing an exoscope to remove the extracanalicular component and an endoscope to remove the intracanalicular component under direct visualisation of the fundus. EETA is a viable option for treating recurrent VS, as it enables enhanced visualisation of both extra- and intracanalicular lesions, including the fundus.

Anterior foramen magnum (AFM) meningiomas are difficult to treat because they are situated in anatomically complex regions. One of the most common approaches for AFM meningiomas is the far lateral approach. We describe our exo- and endoscopic two-step approach (EETA) through suboccipital craniotomy. An exoscope is used to remove the tumour's lateral part, whereas an endoscope is used to remove the residual tumour in the exoscope's blind spots, including the brainstem's ventral side. EETA is a viable option for treating AFM meningiomas because it provides an adequate surgical field of view and is minimally invasive.

Primary ciliary dyskinesia (PCD) is a congenital disease caused by gene mutations linked to ciliary dysfunction. PCD causes different symptoms, including chronic sinusitis, infertility, situs inversus and hydrocephalus. Motile cilia on ventricular ependymal cells are a crucial factor in cerebrospinal fluid circulation, and dysfunction of these cells causes hydrocephalus. Deleted in primary ciliary dyskinesia (Dpcd) is one genetic abnormality known to cause PCD, and its knockout leads to hydrocephalus in mice. PCD occurs in Dpcd -/- mice because of the lack of an inner dynein arm (IDA) in the motile cilia. However, how this deficiency is associated with the motility of ventricular ependymal motile cilia in Dpcd -/- mice has not been demonstrated. Herein, we show that Dpcd induces partial defects in dyneins and aberrant motility in ventricular ependymal cilia. In Dpcd -/- mice, the ependymal cilia demonstrated decreased amplitude, abnormal waveforms and low cerebrospinal fluid flow velocity. In addition, the amount of dynein axonemal heavy chains in some IDAs decreased in the ependymal cilia. In wild-type mice, Dpcd was localised in the cytoplasm and cilia of ependymal cells. Thus, abnormal ciliary movement in Dpcd -/- mice is likely attributed to a defect in IDA assembly in the ependymal cilia.

Tumor treating fields (TTFields) treatment has been an important option for the treatment of glioblastoma. The introduction of novel treatment options may lead to distinct recurrence patterns compared to those observed with conventional therapies; however, the specific recurrence pattern during TTFields treatment has not been elucidated. Here, we analyzed 39 cases of glioblastoma treated with TTFields. Although a usage rate of more than 75

Myxoid glioneuronal tumour (MGNT) is a new WHO classification of brain tumours and is defined as tumours with PDGFRA p.K385 mutations. MGNT has a predilection for the septum pellucidum, their clinical features have not yet been clarified because only a few reports exist. In this report, we present the case of a patient with an MGNT that was suitable for endoscopic resection. We discuss the clinical characteristics of MGNTs discovered during a literature review. A 19-year-old female presented with a worsening headache and a disturbance of consciousness. Head MRI revealed a mass lesion in the septum pellucidum and severe obstructive hydrocephalus. She underwent neuroendscopic surgery under general anaesthesia, and near total resection was achieved. Her symptoms improved immediately after surgery, and she was discharged without any morbidities. Pathological examination and genetic testing confirmed the diagnosis of an MGNT. A literature review revealed that 7 of 18 MGNTs developed in the septum pellucidum. Three patients had disseminated lesions at initial diagnosis, and one showed dissemination during the follow-up period. Among the 14 patients who underwent tumour resection surgery, 3 experienced recurrence or regrowth and required additional treatments. All 18 patients were alive at the last follow-up. An MGNT is a tumour that predominantly affects young people and is currently considered to have a good prognosis. However, close postoperative observation is needed because an MGNT often disseminates intracranially and/or into the spinal cord. In addition, we believe that MGNTs located in the septum pellucidum are good candidates for endoscopic resection.