Neurofibromatosis 2-related schwannomatosis is a rare genetic disorder marked by the development of multiple central nervous system tumors and, occasionally, non-hydrocephalic intracranial hypertension. This report details two cases of papilledema in patients with neurofibromatosis 2-related schwannomatosis, characterized by normal ventricular morphology on Magnetic resonance imaging and refractory to conservative treatment. Both patients-a 23-year-old and a 31-year-old female-demonstrated complete resolution of papilledema and restoration of visual function following ventriculoperitoneal shunt placement. These cases underscore the critical role of early ventriculoperitoneal surgical intervention in mitigating vision loss and emphasize the necessity for rigorous clinical surveillance in this unique patient population.

Background/Objectives: WHO grade II meningiomas exhibit heterogeneous clinical behavior that cannot be predicted by conventional histology. This study examined the relationship between the tumor immune microenvironment (TIME) and tumor growth kinetics in order to establish a biological basis for more precise risk stratification. Methods: A retrospective cohort of 15 patients was evaluated. Serial preoperative magnetic resonance imaging (MRI) scans were used to calculate the relative growth rate (RGR) and minimize the baseline tumor size. The densities of Iba1-positive macrophages (TAMs) and B7-H3-positive tumor cells were quantified using a deep learning-based image analysis system. Results: Linear correlation analysis showed no significant associations between individual immune components and RGR. However, median-based stratification revealed distinct associations. Tumors with low TAM density or high B7-H3-positive tumor cell density exhibited significantly higher RGR (P = 0.0401). Additionally, a significant inverse relationship was identified between TAM and that of B7-H3-positive tumor cell densities (Spearman’s R = -0.911, P < 0.001). Conclusions: We identified a proliferative "immune-cold" phenotype in WHO grade II meningiomas, which is characterized by low TAM density and high B7-H3-positive tumor cell density. This study extends established molecular frameworks by suggesting that high B7-H3-positive tumor cells proactively contribute to rapid tumor growth. These findings highlight the importance of targeting B7-H3-positive tumor cells when treating malignant meningiomas.

When treating parafalx lesions, the bridging veins or the frontal sinuses can sometimes obstruct access. Preserving these structures to avoid surgical complications is preferred. We described the concept of the selective interhemispheric oblique approach (SIOA), which combines exoscopic and endoscopic visualization with gravity-assisted brain retraction to ensure safe access to the parafalx lesions. The SIOA is a precise and versatile technique for treating parafalx lesions, particularly in anatomically complex areas. With this approach, it’s possible to mitigate risk of venous injury or sinus opening, avoid the retraction of eloquent areas, and obtain excellent surgical outcomes.

Anterior skull base surgery poses challenges including cerebrospinal fluid (CSF) leakage and cosmetic concerns. A novel one-piece bifrontal basal craniotomy using a pericranial flap was developed to improve outcomes. The technique included precise burr hole placement, dura-protective craniotomy, and frontal sinus sealing using a pericranial flap. Reconstruction was stabilized using miniplates and screws, leaving the epidural dead space unfilled and lowering infection risks. This method reduces CSF leakage, enhances reconstruction durability, and preserves cosmetic and functional outcomes, offering a reliable approach for anterior skull base surgery.

Li-Fraumeni syndrome (LFS) is an autosomal dominant tumor predisposition syndrome caused by heterozygous germline mutations or deletions in the TP53 tumor suppressor gene. Central nervous system tumors, such as choroid plexus tumors, medulloblastomas, and diffuse gliomas, are frequently found in patients with LFS. Although molecular profiles of diffuse gliomas that develop in pediatric patients with LFS have been elucidated, those in adults are limited. Recently, diffuse gliomas have been divided into pediatric- and adult-type gliomas, based on their distinct molecular profiles. In the present study, we investigated the molecular profiles of high-grade gliomas in three adults with LFS. These tumors revealed characteristic histopathological findings of high-grade glioma or glioblastoma and harbored wild-type IDH1/2 according to whole exome sequencing (WES). However, these tumors did not exhibit the key molecular alterations of glioblastoma, IDH-wildtype such as TERT promoter mutation, EGFR amplification, or chromosome 7 gain and 10 loss. Although WES revealed no other characteristic gene mutations or copy number alterations in high-grade gliomas, such as those in histone H3 genes, PDGFRA amplification was found in all three cases together with uniparental disomy of chromosome 17p, where the TP53 gene is located. DNA methylation analyses revealed that all tumors exhibited DNA methylation profiles similar to those of pediatric-type high-grade glioma H3-wildtype and IDH-wildtype (pHGG H3-/IDH-wt), RTK1 subtype. These data suggest that high-grade gliomas developed in adult patients with LFS may be involved in pHGG H3-/IDH-wt. PDGFRA and homozygous alterations in TP53 may play pivotal roles in the development of this type of glioma in adult patients with LFS.

Craniopharyngioma (CP) and Rathke's cleft cyst (RCC) are both suprasellar lesions. They are sometimes difficult to distinguish due to their similar findings. We report a case of papillary craniopharyngioma (pCP) with the clinical findings suggesting RCC. A 42-year-old female with intellectual disability presented to our hospital with severe visual dysfunction. Preoperative images revealed a suprasellar cystic lesion without calcification. We performed transsphenoidal surgery. Since the cyst had condensed-milk-like content suggesting RCC, we performed cyst fenestration and wash without removal of the cyst wall. Thereafter, we found fish-egg-like structures on the cyst wall. The histopathological analysis revealed that they had papillary structures surrounded by hyperplastic squamous epithelium with parakeratosis. Immunostaining for BRAF V600E was positive, leading to the diagnosis of pCP. After the surgery, her visual function improved and follow-up Magnetic resonance imaging at 18 months postoperatively showed no apparent recurrence. The presence of condensed-milk-like content suggests a likelihood of RCC indicating that aggressive resection may not be necessary. In contrast, the existence of fish-egg-like structures suggests pCP and requires careful follow-up.

BackgroundPosterior clinoid process (PCP) meningioma is an exceedingly rare entity. It remains the most challenging skull base lesion for neurosurgeons due to its treacherous location that insinuates amongst critical neurovascular structures. This article will describe the technical notes using the endoscopic endonasal approach that provide the earliest devascularization and detachment of the tumor PCP meningioma.MethodsWe are introducing the surgical implementation of an endoscopic endonasal approach to removing PCP meningioma. Furthermore, we perform a literature review of posterior clinoid process meningioma that undergoes surgical intervention, then summarize the benefits and limitations of each approach.ResultsWe present a case of right PCP meningioma that was removed using an endoscopic endonasal approach through the transposterior clinoid corridor in a 52-year-old-woman. We describe the technical notes in performing this approach to have the earliest devascularization and detachment of the tumor by performing posterior clinoidectomy. Safe tumor removal is performed with a wide and clear view of the surrounding neurovascular structure. Based on our database search, we found nine articles reported on the surgical management of PCP meningiomas, with a total number of 15 cases. All of the reported cases performed the tumor removal using the transcranial approach.ConclusionThe endoscopic endonasal transposterior clinoid approach circumvents all disadvantages faced by the traditional transcranial approach, providing the earliest approach to devascularized and detaching the tumor from its attachment at PCP. This approach demonstrates safety and efficacy, making it an acceptable alternative for PCP meningioma resections.

OBJECTIVE:Surgical treatment of brainstem cavernous malformations (CMs) is challenging. Surgery using the endoscopic transsphenoidal transclival approach (eTSTCA) is reported as a useful alternative for ventral brainstem CMs. However, CMs located in the ventral midline of the brainstem are rare, and only a small number of case reports on these CMs treated with the eTSTCA exist. The efficacy and safety of the eTSTCA have not yet been fully examined. METHODS:A retrospective analysis was performed for 5 consecutive patients who underwent surgery via the eTSTCA for treating ventral pontine CMs. RESULTS:The average maximum CM diameter was 26.0 mm (18-38 mm). All patients underwent MR-diffusion tensor imaging, which confirmed that the corticospinal tract (CST) deviated posteriorly or laterally to the CM. Direct brainstem cortical stimulation was performed to localize the CST before making the cortical incision. After the excision of the CM, the cavity was filled with artificial CSF to make an aqueous surgical field (wet-field technique) for observing the tumor cavity and confirming complete hemostasis and resection. Total removal was achieved in all patients. The preoperative modified Rankin Scale score was 3 in 3 patients and 4 in 2 patients, whereas it was 1 in 2 patients and 0 in 3 patients 3 months after surgery. Postoperative CSF leakage was observed in 1 patient, and transient abducens nerve palsy was observed in 1 patient. No other intra- or postoperative complications were observed. CONCLUSIONS:MR-diffusion tensor imaging and direct brainstem cortical stimulation were useful to ascertain the proximity of the CST to the CM. The endoscope provides a clear view even underwater, and it was safe and effective to observe the entire CM cavity and confirm complete hemostasis without additional retraction of the brainstem parenchyma, including the CST. The eTSTCA provides a direct access point to the lesion and may be a safer alternative treatment for patients whose CST deviates laterally or posteriorly to the CM.

OBJECTIVE:This study aimed to evaluate the efficacy and safety of combination therapy with bevacizumab (Bev), irinotecan (CPT-11), and temozolomide (TMZ) in children with central nervous system (CNS) embryonal tumor relapse.METHODS:The authors retrospectively examined 13 consecutive pediatric patients with relapsed or refractory CNS embryonal tumors who received combination therapy comprising Bev, CPT-11, and TMZ. Specifically, 9 patients had medulloblastoma, 3 had atypical teratoid/rhabdoid tumor (AT/RT), and 1 had CNS embryonal tumor with rhabdoid features. Of the 9 medulloblastoma cases, 2 were categorized in the Sonic hedgehog subgroup and 6 in molecular subgroup 3 for medulloblastoma.RESULTS:The complete and partial objective response rates were 66.6% in patients with medulloblastoma and 75.0% in patients with AT/RT or CNS embryonal tumors with rhabdoid features. Furthermore, the 12- and 24-month progression-free survival rates were 69.2% and 51.9% for all patients with recurrent or refractory CNS embryonal tumors, respectively. In contrast, the 12- and 24-month overall survival rates were 67.1% and 58.7%, respectively, for all patients with relapsed or refractory CNS embryonal tumors. The authors observed grade 3 neutropenia, thrombocytopenia, proteinuria, hypertension, diarrhea, and constipation in 23.1%, 7.7%, 23.1%, 7.7%, 7.7%, and 7.7% of patients, respectively. Furthermore, grade 4 neutropenia was observed in 7.1% of patients. Nonhematological adverse effects, such as nausea and constipation, were mild and controlled with standard antiemetics.CONCLUSIONS:This study demonstrated favorable survival outcomes in patients with relapsed or refractory pediatric CNS embryonal tumors and thus helped to investigate the efficacy of combination therapy comprising Bev, CPT-11, and TMZ. Moreover, combination chemotherapy had high objective response rates, and all adverse events were tolerable. To date, data supporting the efficacy and safety of this regimen in the relapsed or refractory AT/RT population are limited. These findings suggest the potential efficacy and safety of combination chemotherapy in patients with relapsed or refractory pediatric CNS embryonal tumors.

A 57‐year‐old man had trigeminal schwannoma in Meckel's cave with eyelid myokymia only. The evaluation of the trigeminal‐evoked blink reflex was useful for confirming eyelid myokymia and contributed to surgical decision‐making. In patients with persistent eyelid myokymia, neurophysiological and imaging evaluations may be useful for determining the underlying pathophysiology.

Spheno-orbital meningiomas (SOMs) are complex tumors that grow and extend into nearby structures. SOM tumor growth is often associated with hyperostosis caused by tumor cell infiltration and bone alteration. We describe the case of a 64-year-old man with SOM that extended into the sphenoid sinus without a direct connection between the intracranial and extracranial lesions. This report emphasizes the importance of identifying the growth patterns of SOMs and assessing the paranasal sinuses adjacent to the hyperostotic orbit walls from preoperative images.

IntroductionThe pituitary gland, regulating various hormones, is central in the endocrine system. As spontaneous recovery from hypopituitarism is rare, and exogenous-hormone substitution is clumsy, pituitary replacement via regenerative medicine, using pluripotent stem cells, is desirable. We have developed a differentiation method that in mice yields pituitary organoids (POs) derived from human embryonic stem cells (hESC). Efficacy of these POs, transplanted subcutaneously into hypopituitary mice, in reversing hypopituitarism was studied.MethodshESC-derived POs were transplanted into inguinal subcutaneous white adipose tissue (ISWAT) and beneath dorsal skin, a relatively avascular region (AR), of hypophysectomized severe combined immunodeficient (SCID) mice. Pituitary function was evaluated thereafter for ¾ 6mo, assaying basal plasma ACTH and ACTH response to corticotropin-releasing hormone (CRH) stimulation. Histopathologic examination of organoids 150d after transplantation assessed engraftment. Some mice received an inhibitor of vascular endothelial growth factor (VEGF) to permit assessment of how angiogenesis contributed to subcutaneous engraftment.ResultsDuring follow-up, both basal and CRH-stimulated plasma ACTH levels were significantly higher in the ISWAT group (p < 0.001 – 0.05 and 0.001 – 0.005, respectively) than in a sham-operated group. ACTH secretion also was higher in the ISWAT group than in the AR group. Histopathologic study found ACTH-producing human pituitary-cell clusters in both groups of allografts, which had acquired a microvasculature. POs qPCR showed expression of angiogenetic factors. Plasma ACTH levels decreased with VEGF-inhibitor administration.ConclusionsSubcutaneous transplantation of hESC-derived POs into hypopituitary SCID mice efficaciously renders recipients ACTH-sufficient.

The pathophysiology of neurovascular compression syndrome has not been fully elucidated, and cerebrospinal fluid levels of nerve tissue-related markers involved in this disorder have not yet been reported. We measured cerebrospinal fluid levels of S100B protein, neuron-specific enolase, and myelin basic protein in 21 patients with trigeminal neuralgia, 9 patients with hemifacial spasms, and 10 patients with non-ruptured intracranial aneurysms (control). Cerebrospinal fluid levels of these markers were determined using commercially available assay kits. Both trigeminal neuralgia and hemifacial spasm groups showed significantly increased cerebrospinal fluid levels of S100B compared with the control group (1120 [IQR 391–1420], 766 [IQR 583–1500], and 255 [IQR 190–285] pg/mL, respectively; p = 0.001). There were no statistically significant differences in cerebrospinal fluid levels of neuron-specific enolase or myelin basic protein among the groups. Cerebrospinal fluid S100B levels were significantly higher in patients with trigeminal neuralgia and hemifacial spasm than in controls, which suggests the involvement of S100B in the underlying pathophysiology of neurovascular compression syndrome.

Sinus pericranii (SP) located in the superior eyelid is an unusual clinical presentation. Here, we report a case of 72-year-old woman with an unruptured cerebral aneurysm presented with an SP located in the left superior eyelid. The SP was found to have a dominant venous outflow from the bilateral frontal region with an arterialized blood flow pattern on color Doppler ultrasonography (CDUS). During the aneurysmal surgery, intraoperative monitoring of the dominant venous outflow with CDUS was useful for the prevention of venous outflow obstruction. Physicians should carefully consider intracranial vascular anomalies in the differential diagnosis of vascular lesions of the superior eyelid.

Background and Objective: Skull base chordomas are clinically malignant because of the difficulty of total removal, high recurrence rate, and occasional drop metastasis. Although aggressive surgical resection and postoperative radiation have been recommended, the long-term outcome remains unsatisfactory.Methods: From 1992 to 2011, we treated 24 patients with skull base chordoma using aggressive surgical removal as a principal strategy. Skull base approaches were selected according to tumor extension to remove the tumor and surrounding bone as completely as possible. After surgery, all patients were closely observed with MRI to find small and localized recurrent tumors, which were treated with gamma-knife radiosurgery or surgical resection. The mean postoperative follow-up duration was 10.2 years (range, 1-17.2 years).Results: The 5-, 10-, and 15-year overall survival rates were 86%, 72%, and 72%, respectively. The 5- and 10-year progression-free survival rates were 47% and 35%, respectively. Tumor extension to the brainstem and partial tumor removal were the factors related to poor survival.Conclusions: Our results suggest that aggressive surgical removal improves the long-term outcome of patients with skull base chordoma. We would like to emphasize that skull base chordomas should be aggressively removed using various skull base approaches.

The purpose of this study was to carry out a program of Cognitive Behavioral Therapy (CBT) based on the pain sustainment/exacerbation model for tension-type headache (TTH) patients and to examine the effectiveness as a pilot study. The participants were 4 TTH patients who consulted the outpatient clinic of a university hospital. It consisted of 4 individualized sessions as CBT program (including psychological education, self-monitoring, relaxation technique, cognitive restricting and exposure), and a follow-up examination was carried out 1 month after its completion. The sessions, each of which was 60 minutes long, were executed at weekly intervals. As a result, the score of the Pain Catastrophizing Scale (PCS) decreased after program compared with before program in all patients. The score of escape/avoidance was also reduced at the post-program and follow-up (1 month later) compared with the score of pre-program in patients except Case 2, in whom the score was 0 throughout the study. The degree of the Headache Impact Test (HIT-6) improved by program and changed to "mild" or "none" in all participants. These findings show that in patients with TTH this short CBT program has effect on pain catastrophizing, escape/avoidance and daily disability.

OBJECTIVE AND IMPORTANCE:We describe a new endoscopic technique, the dual-endoscopic method, in which two independent endoscopic systems are simultaneously used in the subtemporal space and intraparenchymal field for patients with pontine cystic tumours. Tumours were successfully removed through a sheath placed in the brainstem via the subtemporal keyhole approach, with safety ensured by the second subtemporal endoscope.CLINICAL PRESENTATION:A purely endoscopic subtemporal approach was performed in three cases of pontine cystic tumour, including two low-grade gliomas and a recurrent chordoma. The gliomas showed nodules. Recurrent chordoma consisted of a mucinous component.TECHNIQUE:Using a keyhole subtemporal approach and a 4.0-mm rigid endoscope with a high-definition camera, a transparent puncture needle containing a 2.7-mm rigid endoscope was inserted into the cyst. The tumour was removed using suction, biopsy forceps, and scissors simultaneously placed with the 2.7-mm endoscope in a transparent sheath.CONCLUSION:Since the 4.0-mm endoscope placed in the subtemporal space monitored all procedures of the 2.7-mm endoscope, tumour removal was performed safely without damaging the pons, cranial nerves, or vessels. We safely and successfully removed a cystic pontine tumour using a dual-endoscopic method. This new method ensures the safety of deep-seated endoscopic procedures via a minimally invasive transcranial approach.

We quantified the subarachnoid hemorrhage (SAH) volume in 64 patients on three-dimensional computed tomography (3D-CT) scans and studied the correlation between the SAH volume and the occurrence of symptomatic vasospasm (SVS). We studied 64 patients with SAH onset (day 0) and on days 1, 4, 7, and 14. We compared the hematoma volume by 3D-CT with 2D-CT on day 0 and examined the correlation between the hematoma volume and the occurrence of SVS. The hematoma volume, including the volume of normal structures, was automatically calculated (V1). The volume of normal structures manifesting identical CT numbers was previously calculated in patients without intracranial lesions (V2). The total hematoma volume was defined as V1 minus mean value of V2 (= 12 ml). The mean hematoma volume by 3D-CT was 48 ± 12 ml and by 2D-CT was 31 ± 45 ml (mean ± SD, n = 64). The hematoma volume was significantly larger by 3D-CT than by 2D-CT (p < 0.05). At all time points, the hematoma volumes were significantly larger in patients with than without SVS. We developed a new method for the quantitative determination of the SAH volume by 3D-CT. This method may allow us to quantify the volume of SAH in clinical studies of cerebral vasospasm.