Adenoid glioblastoma: Stromal hypovascularity and secretion of chondromodulin-I by tumor cells.

The case of a 75-year-old man with a glioblastoma of the right frontal lobe showing features of adenoid glioblastoma is reported. The tumor consisted of two components: the adenoid component, in which large, cohesive, polygonal cells with vesicular nuclei and abundant basophilic cytoplasm showed nest-like, trabecular, or tubular growth on the myxoid matrix and formed a multinodular configuration; and the subsidiary component, in which short spindle cells showed compact fascicular growth. The features of ordinary glioblastoma were also found in a small area. Tumor cells were immunoreactive for S-100 protein, glial fibrillary acidic protein, and Olig2, and some tumor cells in the adenoid component showed immunoreactivity for cytokeratins and E-cadherin. A marked regional decrease in microvascular density, approaching almost complete absence of microvessels, was demonstrated in the adenoid component. In contrast, microvascular density was well preserved in the spindle cell component and the area of ordinary glioblastoma. Tumor cells in the adenoid component showed cytoplasmic expression of chondromodulin-I, one of the cytokines that strongly inhibit angiogenesis, whereas the expression of this protein was very weak or only faint in the spindle cell component and the area of ordinary glioblastoma. A marked regional decrease in microvascular density was associated with myxoid change of the stroma and considered to be caused by the secretion of chondromodulin-I by tumor cells. Stromal hypovascularity with myxoid change might play an important role in the morphogenesis of adenoid features.

H3 K27-altered diffuse midline glioma of the thalamus with formation of glio-fibrillary globular structures.

A case of diffuse midline glioma (DMG), H3 K27-altered, that arose in the right thalamus of a 14-year-old boy is reported. The patient died of tumor spread after a progressive clinical course of approximately 13 months. Histopathologically, the tumor consisted of a mixture of loose proliferation of stellate cells and compact fascicular growth of spindle cells showing a "piloid" feature. Aggregates of globular structures composed of entangled fine glial fibrils ("glio-fibrillary globules, GFGs") were observed. Tumor cells were immunoreactive for S-100 protein and glial fibrillary acidic protein (GFAP), and showed nuclear immunoreactivity for histone H3 K27M and loss of expression of H3 K27me3. Tumor cell nuclei were also negative for alpha-thalassemia/mental retardation syndrome X-linked protein (ATRX) and p16. Although GFGs morphologically resembled "neuropil-like islands" or "neurocytic rosettes" seen in glial or glio-neuronal tumors, they showed immunoreactivity for GFAP, but not for synaptophysin. A GFG is a unique structure that has been described in DMG, H3 K27-altered, by a few investigators. To the best of our knowledge, this structure has not previously been reported in other glial or glio-neuronal tumors. It could be added as a new feature in the histopathological variations of DMG, extending its morphological spectrum. Familiarity with this feature can help prevent misdiagnosis of DMG.

Neuroradiological, genetic and clinical characteristics of histone H3 K27-mutant diffuse midline gliomas in the Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network): multicenter retrospective cohort.

This study aims to elucidate the clinical and molecular characteristics, treatment outcomes and prognostic factors of patients with histone H3 K27-mutant diffuse midline glioma. We retrospectively analyzed 93 patients with diffuse midline glioma (47 thalamus, 24 brainstem, 12 spinal cord and 10 other midline locations) treated at 24 affiliated hospitals in the Kansai Molecular Diagnosis Network for CNS Tumors. Considering the term "midline" areas, which had been confused in previous reports, we classified four midline locations based on previous reports and anatomical findings. Clinical and molecular characteristics of the study cohort included: age 4-78 years, female sex (41%), lower-grade histology (56%), preoperative Karnofsky performance status (KPS) scores ≥ 80 (49%), resection (36%), adjuvant radiation plus chemotherapy (83%), temozolomide therapy (76%), bevacizumab therapy (42%), HIST1H3B p.K27M mutation (2%), TERT promoter mutation (3%), MGMT promoter methylation (9%), BRAF p.V600E mutation (1%), FGFR1 mutation (14%) and EGFR mutation (3%). Median progression-free and overall survival time was 9.9 ± 1.0 (7.9-11.9, 95% CI) and 16.6 ± 1.4 (13.9-19.3, 95% CI) months, respectively. Female sex, preoperative KPS score ≥ 80, adjuvant radiation + temozolomide and radiation ≥ 50 Gy were associated with favorable prognosis. Female sex and preoperative KPS score ≥ 80 were identified as independent good prognostic factors. This study demonstrated the current state of clinical practice for patients with diffuse midline glioma and molecular analyses of diffuse midline glioma in real-world settings. Further investigation in a larger population would contribute to better understanding of the pathology of diffuse midline glioma.

Cerebral vasospasm occurring immediately after endoscopic transsphenoidal resection of a pituitary adenoma: A case report.

Background: Cerebral vasospasm is a rare postoperative complication of transsphenoidal pituitary adenoma surgery with potentially severe consequences. These vasospasms generally have a delayed presentation at a mean of 8 postoperative days. We report an unusual case of hyperacute onset of cerebral vasospasm that occurred immediately after surgery. Case Description: A 38-year-old man underwent endoscopic transsphenoidal surgery for a nonfunctioning pituitary adenoma. The patient experienced mild subarachnoid hematoma during surgery. Three hours after surgery, he developed rightward conjugate eye deviation and complete paralysis of the left upper and lower extremities. Diagnostic imaging revealed cerebral vasospasm in both middle cerebral arteries, and symptoms improved after intra-arterial administration of fasudil hydrochloride. Conclusion: There is a need for prompt diagnosis and therapeutic intervention when typical symptoms of cerebral vasospasm, such as paralysis, occur at any time during the postoperative course.

Prediction of MGMT promotor methylation status in glioblastoma by contrast-enhanced T1-weighted intensity image.

Background: The study aims to explore MRI phenotypes that predict glioblastoma's (GBM) methylation status of the promoter region of MGMT gene (pMGMT) by qualitatively assessing contrast-enhanced T1-weighted intensity images. Methods: A total of 193 histologically and molecularly confirmed GBMs at the Kansai Network for Molecular Diagnosis of Central Nervous Tumors (KANSAI) were used as an exploratory cohort. From the Cancer Imaging Archive/Cancer Genome Atlas (TCGA) 93 patients were used as validation cohorts. "Thickened structure" was defined as the solid tumor component presenting circumferential extension or occupying >50% of the tumor volume. "Methylated contrast phenotype" was defined as indistinct enhancing circumferential border, heterogenous enhancement, or nodular enhancement. Inter-rater agreement was assessed, followed by an investigation of the relationship between radiological findings and pMGMT methylation status. Results: Fleiss's Kappa coefficient for "Thickened structure" was 0.68 for the exploratory and 0.55 for the validation cohort, and for "Methylated contrast phenotype," 0.30 and 0.39, respectively. The imaging feature, the presence of "Thickened structure" and absence of "Methylated contrast phenotype," was significantly predictive of pMGMT unmethylation both for the exploratory (p = .015, odds ratio = 2.44) and for the validation cohort (p = .006, odds ratio = 7.83). The sensitivities and specificities of the imaging feature, the presence of "Thickened structure," and the absence of "Methylated contrast phenotype" for predicting pMGMT unmethylation were 0.29 and 0.86 for the exploratory and 0.25 and 0.96 for the validation cohort. Conclusions: The present study showed that qualitative assessment of contrast-enhanced T1-weighted intensity images helps predict GBM's pMGMT methylation status.

Giant cell glioblastoma with lipogenic differentiation in a patient with neurofibromatosis type 1: A case report.

A 45-year-old woman with neurofibromatosis type 1 (NF1) developed a tumor in the left frontal lobe that showed features of giant cell glioblastoma (GC-GB). In addition to the typical GC-GB features, the tumor showed lipogenic differentiation, with many atypical lipoblasts and mature adipocytes. Tumor cells, including the lipogenic cells, were immunoreactive for GFAP, S-100 protein, ATRX, and p53. They were negative for IDH1-R132H, BRAF V600E, synaptophysin, NeuN, p16, mismatch repair proteins, and CD34. The patient is free from recurrence at approximately two years postoperatively. This is the fifth reported case of NF1-associated GC-GB (the second adult case). NF1 gene mutation might have played a role in the pathogenesis of lipogenic differentiation of GC-GB. The differential diagnosis of lipidized GC-GB from gliosarcoma or anaplastic pleomorphic xanthoastrocytoma is briefly discussed.

Survey of medications for myelomeningocele patients over their lifetime in Japan.

BACKGROUND: This study aimed to investigate medication prescriptions for patients with myelomeningocele (MMC) across different age groups, particularly in adulthood and after middle age. METHODS: The Japan Medical Data Center (JMDC) database, based on medical claims data, was utilized for this analysis. Patients were divided into 10-year age groups, and prescriptions for analgesics, anticonvulsants, psychotropic drugs, lifestyle disease-related drugs, drugs for urinary incontinence, and laxatives were examined. To compare the differences in the utilization of medications unrelated to lifestyle-related diseases across different age groups, the data was categorized into three age groups: 19 or under, 20-39, and 40 or older. RESULTS: Among the 556 MMC patients, the percentage of those regularly prescribed analgesics increased from 2.8% in patients ≤ 19 to 31.7% in patients 40 or older (p < 0.01). Psychotropic medication use also increased with age, rising significantly from 6.3% in patients ≤ 19 to 34.6% in patients 40 or older (p < 0.01). Patients with MMC showed an increasing trend in prescriptions for lifestyle-related disease medications compared to the normal control group. Notably, the percentage of patients in their 30 s taking hypertension medication was 4.9%, significantly higher than the 0.86% in the control group (p = 0.029). In their 40 s, 22.9% of MMC patients were prescribed hyperlipidemia medication, significantly higher than the 3.9% in the control group (p < 0.01). CONCLUSION: Comprehensive multidisciplinary support and follow-up are crucial to enhance the quality of life for MMC patients, with particular attention to pain management, psychological care, and treatment of lifestyle-related diseases.

5-Aminolevulinic acid fluorescence-guided endoscopic surgery for deep-seated intraparenchymal tumors.

AIM: The usefulness of 5-aminolevulinic acid (5-ALA) fluorescence-assisted surgery for maximum resection of malignant gliomas has been established. However, its usefulness when combined with endoscopic surgery for deep-seated tumors has not been well established. In this study, whether 5-ALA photodynamic diagnosis (PDD) is feasible and useful for endoscopic surgery was investigated. METHODS: A specially designed endoscope for PDD that delivers white light or blue light (375-440 nm) as excitation light was used. The fluorescence emitted by the tumor was evaluated in the cavity during resection or at the tip of the sheath during biopsy. The intensity of fluorescence was classified into three categories: strong, vague, and negative. RESULTS: A total of 30 intraparenchymal tumors were observed with a neuroendoscope and 5-ALA PDD; 16 patients underwent resection, and 14 underwent biopsy. Overall, 67% (20/30) of tumors showed positive fluorescence of protoporphyrin IX. High-grade gliomas (HGGs) including glioblastoma (GBM) and anaplastic astrocytoma (AA) showed strong fluorescence in 47% (7/15), vague fluorescence in 33% (5/15), and negative fluorescence in 20% (3/15) of cases. Low-grade gliomas (LGGs) showed vague fluorescence in 33% (1/3) and negative fluorescence in 67% (2/3). Diffuse large B-cell lymphoma (DLBCL) showed vague fluorescence in 38% (3/8) and negative fluorescence in 63% (5/8). Metastatic tumors showed strong fluorescence in 25% (1/4) and vague fluorescence in 75% (3/4). In the comparison of fluorescence evaluation, a significant difference was observed only in the comparison between HGGs and DLBCL (p = 0.049). CONCLUSION: These results suggest that 5-ALA PDD-assisted endoscopic surgery is feasible and useful for deep-seated intraparenchymal tumors.

Distinct patterns of copy number alterations may predict poor outcome in central nervous system germ cell tumors.

We have previously reported that 12p gain may predict the presence of malignant components and poor prognosis for CNS germ cell tumor (GCT). Recently, 3p25.3 gain was identified as an independent predictor of poor prognosis for testicular GCT. Eighty-one CNS GCTs were analyzed. Copy number was calculated using methylation arrays. Five cases (6.2%) showed 3p25.3 gain, but only among the 40 non-germinomatous GCTs (NGGCTs) (5/40, 12.5%; p = 0.03). Among NGGCTs, those with a yolk sac tumor component showed a significantly higher frequency of 3p25.3 gain (18.2%) than those without (1.5%; p = 0.048). NGGCTs with gain showed significantly shorter progression-free survival (PFS) than those without (p = 0.047). The 3p25.3 gain and 12p gain were independent from each other. The combination of 3p25.3 gain and/or 12p gain was more frequent among NGGCTs with malignant components (69%) than among those without (29%; p = 0.02). Germinomas containing a higher number of copy number alterations showed shorter PFS than those with fewer (p = 0.03). Taken together, a finding of 3p25.3 gain may be a copy number alteration specific to NGGCTs and in combination with 12p gain could serve as a marker of negative prognosis or treatment resistance. Germinoma with frequent chromosomal instability may constitute an unfavorable subgroup.

Refractory Delayed Pneumocephalus after Transsphenoidal Cyst Drainage for Rathke's Cleft Cyst in a Patient with a Cerebrospinal Fluid Shunt.

A 75-year-old man presented with bilateral lower limb weakness to our hospital from another clinic. Radiological examinations implied the possibilities of idiopathic normal pressure hydrocephalus (iNPH) and a suprasellar cyst, but both were observed conservatively at that time. Due to the progressive gait disturbance, a lumboperitoneal shunt was implanted 1 year later. The clinical symptoms improved, but the cyst had grown after another year, causing visual impairment. Transsphenoidal drainage of the cyst was performed, but delayed pneumocephalus occurred. Repair surgery was performed with temporary suspension of shunt function, but pneumocephalus relapsed two and a half months after the resumption of shunt flow. In the second repair surgery, the shunt was removed because it was assumed that it would prevent closure of the fistula by lowering intracranial pressure. Two and a half months later, after confirming involution of the cyst and no pneumocephalus, a ventriculoperitoneal shunt was implanted, and cerebrospinal fluid (CSF) leakage has not relapsed since then. The coexistence of idiopathic normal pressure hydrocephalus (iNPH) and Rathke's cleft cyst (RCC) is rare, but it can occur. RCC can be cured by simple drainage, but delayed pneumocephalus can occur in cases whose intracranial pressure decreases due to CSF shunting. When simple drainage without sellar reconstruction for RCC is attempted after CSF shunting for coexistent iNPH, attention should be paid to changes in intracranial pressure, and it is desirable to stop the flow of the shunt for a certain period.

A case of acute hydrocephalus due to a giant prolactinoma rescued by transventricular neuroendoscopic tumorectomy.

Background: A giant prolactinoma extending to the suprasellar area and causing hydrocephalus may be life-threatening and should be treated promptly. A case of a giant prolactinoma with acute hydrocephalus that underwent transventricular neuroendoscopic tumor resection followed by cabergoline administration is presented. Case Description: A 21-year-old man had a headache lasting for about a month. He gradually developed nausea and disturbance of consciousness. Magnetic resonance imaging showed a contrast-enhanced lesion that extended from the intrasellar space to the suprasellar space and into the third ventricle. The tumor obstructed the foramen of Monro and caused hydrocephalus. A blood test showed marked elevation of prolactin (16,790 ng/mL). The tumor was diagnosed as a prolactinoma. The tumor in the third ventricle had formed a cyst, and the cyst wall blocked the right foramen of Monro. The cystic component of the tumor was resected using an Olympus VEF-V flexible neuroendoscope. The histological diagnosis was pituitary adenoma. The hydrocephalus improved rapidly and his consciousness became clear. After the operation, he was started on cabergoline. The tumor size subsequently decreased. Conclusion: Prompt partial resection of the giant prolactinoma by transventricular neuroendoscopy resulted in early improvement of hydrocephalus with less invasiveness, allowing subsequent treatment with cabergoline.

Comparison of intraoperative neurophysiological monitoring methods for lumbosacral lipoma surgery in infants.

BACKGROUND: Stable intraoperative neurophysiology monitoring of infants, especially very young infants, is challenging. In this study, motor evoked potentials (MEPs), the bulbocavernosus reflex (BCR), and somatosensory evoked potentials (SEPs) were simultaneously monitored in infants with lumbosacral lipomas, and these methods were compared retrospectively. METHODS: A total of 21 surgeries performed for lumbosacral lipoma in patients less than 1 year old were studied. The mean age at surgery was 133.8 days (range 21-287 days; ≤ 120 days: 9 cases, > 120 days: 12 cases). Transcranial MEPs were measured in the anal sphincter and gastrocnemius, and tibialis anterior and other muscles were added as needed. The BCR was measured by the electromyogram of the anal sphincter muscle with stimulation of the pubic region, and SEPs were measured from the waveforms of stimulation of the posterior tibial nerves. RESULTS: For the BCR, stable potentials could be recorded for all 9 cases at ≤ 120 days of age. In contrast, for MEPs, stable potentials could be recorded in only 4 of 9 cases (p < 0.05). For all patients > 120 days of age, MEPs and the BCR were measurable. SEPs were undetectable in some patients regardless of age. CONCLUSION: The BCR could be more consistently measured than MEPs in infant patients with lumbosacral lipoma at ≤ 120 days of age.

Correlations of intracranial pathology and cause of head injury with retinal hemorrhage in infants and toddlers: A multicenter, retrospective study by the J-HITs (Japanese Head injury of Infants and Toddlers study) group.

INTRODUCTION: In infants who have suffered head trauma there are two possible explanations for retinal hemorrhage (RH): direct vitreous shaking and occurrence in association with intracranial lesions. Which possibility is more plausible was examined. MATERIAL AND METHODS: This multicenter, retrospective study reviewed the clinical records of children younger than four years with head trauma who had been diagnosed with any findings on head computed tomography (CT) and/or magnetic resonance imaging (MRI). Of 452 cases, 239 underwent an ophthalmological examination and were included in this study. The relationships of RH with intracranial findings and the cause of injury were examined. RESULT: Odds ratios for RH were significant for subdural hematoma (OR 23.41, p = 0.0004), brain edema (OR 5.46, p = 0.0095), nonaccidental (OR 11.26, p<0.0001), and self-inflicted falls (OR 6.22, p = 0.0041). CONCLUSION: Although nonaccidental, brain edema and self-inflicted falls were associated with RH, subdural hematoma was most strongly associated with RH.

Coexisting filum terminale arteriovenous fistula and filum terminale lipoma treated with single-stage surgery: illustrative case.

BACKGROUND: Both filum terminale arteriovenous fistulas (FTAVFs) and filum terminale lipomas (FTLs) are rare. Because of this rarity, there is a paucity of data regarding concomitant FTAVF and FTL, and the optimal treatment remains to be defined. The authors describe a patient with coexisting FTAVF and FTL treated with single-stage surgery. OBSERVATIONS: A man in his 70s was referred to the authors' department because of a suspected spinal vascular malformation seen on magnetic resonance imaging that was performed to investigate lower limb weakness, intermittent claudication, and urinary incontinence. Previous imaging had shown a terminal lipoma with an internal flow void. Computed tomography angiography and digital subtraction angiography revealed an FTAVF, the feeder being a lateral sacral artery. The patient was treated surgically with curative intent. The FTL and tethered cord that had been identified by imaging were treated in the same procedure. Postoperative digital subtraction angiography showed absence of the abnormal vessels. The patient was discharged home on the 19th postoperative day. LESSONS: When considering treatment, it is important to determine whether symptoms are attributable mainly to FTL, tethered cord, or FTAVF. One-stage treatment is useful because it eliminates both the FTAVF and the factors that led to its development.

The effect of shunt removal on the quality of life in patients with congenital hydrocephalus.

BACKGROUND: Although there have been reports investigating the quality of life of patients who underwent ventriculoperitoneal shunting or endoscopic third ventriculostomy (ETV) for congenital hydrocephalus, there have been no studies of the quality of life of patients after ventriculoperitoneal shunt (VPS) removal. In the present study, a survey of pediatric and congenital hydrocephalus patients was conducted to compare the quality of life of patients with a remaining VPS with that of patients who had the shunt removed. METHODS: Between February 2020 and November 2021, an outpatient survey was administered to patients 8 years of age and older who had undergone VPS due to a diagnosis of congenital hydrocephalus. The Hydrocephalus Outcome Questionnaire (HOQ) was used to assess the quality of life for this study. The HOQ scores (overall health score, physical health score, cognitive health score, and social-emotional health score) were compared among three groups: a VPS-remaining group, VPS-removed with endoscopic third ventriculostomy (ETV) group, and VPS-removed without ETV group. RESULTS: The total number of patients who underwent VPS for hydrocephalus was 71, with 47 in the VPS-remaining group, 14 in the shunt-removed with ETV group, and 10 in the shunt-removed without ETV group. The HOQ overall health score was 0.68 for the VPS-remaining group, 0.74 for the shunt-removed with ETV group, and 0.74 for the shunt-removed without ETV. There were no significant differences between the VPS-remaining group and the VPS-removed with or without ETV groups (p = 0.3255, 0.4178, respectively). CONCLUSION: There was no significant difference in the quality of life between patients with a remaining VPS and those who had their VPS removed with or without ETV.

5-ALA fluorescence-guided resection of pediatric low-grade glioma using the ORBEYE 3D digital exoscope: a technical report.

OBJECTIVE: A case of low-grade glioma in which 5-aminolevulinic acid (5-ALA) fluorescence was visualized by a digital exoscope is presented. CASE PRESENTATION: A 14-year-old girl with recurrent paroxysmal episodes of a strange smell and nausea underwent magnetic resonance imaging (MRI) for further investigation. The MRI showed a tumor with an enhanced nodule in the right temporal lobe. The patient received 5-ALA preoperatively, and intraoperative observation using a 4 K-3-dimension digital exoscope (Olympus ORBEYE) showed that the tumor was fluorescent, which was useful in determining the extent of tumor removal. Postoperative MRI showed that the tumor was completely removed. The histopathological diagnosis was pleomorphic xanthoastrocytoma. She was discharged without any complications. CONCLUSIONS: 5-ALA-fluorescence-guided resection of low-grade glioma using the ORBEYE was useful for determining the extent of removal.

Current status and challenges of neurosurgical procedures for patients with myelomeningocele in real-world Japan.

BACKGROUND: Little is known about the real-world status of neurosurgical treatment of myelomeningocele patients. OBJECTIVE: To investigate the real-world status of neurosurgical treatment of myelomeningocele patients, medical claims data provided by the Japan Medical Data Center (JMDC) were analyzed. METHODS: The health claims data of 556 patients with myelomeningoceles from January 2005 to March 2020 were examined. The number of neurosurgical procedures, including myelomeningocele repair, tethered cord release, cerebrospinal fluid (CSF) shunt, CSF drainage, and endoscopic third ventriculostomy (ETV), was determined. RESULTS: A total of 313 neurosurgical procedures were performed for 135 patients in 74 institutions during the study period. The shunt survival rate was most affected by shunts that were revised when the patient was less than 1 year old, which had a significantly lower survival rate than all of the initial shunts performed when the patient was less than on1 year old; the 1-year shunt survival rate was 35 vs 64% (P = 0.0102). The survival rate was significantly lower in patients younger than 1 year who had CSF drainage before shunting compared to those younger than 1 year who did not have CSF drainage before shunting; the 1-year shunt survival rate was 27 vs 59% (P = 0.0196), and 81% of patients remained free of tethered cord release 10 years later. CONCLUSIONS: In this study, a revised shunt of less than 1 year of age and CSF drainage before shunting were the factors that lowered the shunt survival rate in the real world for CSF shunts for hydrocephalus associated with myelomeningocele.

Newborn with severe supratentorial subdural hematoma due to laceration of the tentorium cerebelli.

PURPOSE: A rare case of a newborn girl born by a normal vaginal delivery who developed a severe supratentorial subdural hematoma due to a laceration in the tentorium cerebelli is presented. METHODS AND RESULTS: The girl, born by normal vaginal delivery at 39 weeks and 4 days of gestation, showed an intermittent decrease in oxygen saturation and bulging of the anterior fontanelle. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a subdural hematoma centered in the left occipital region with a midline shift. Hematoma evacuation with craniotomy was performed, and the source of bleeding was a laceration of the tentorium cerebelli. CONCLUSION: Severe supratentorial subdural hematomas can occur due to laceration of the tentorium cerebelli even in a normal vaginal delivery.