Lipidomic-Based Approach to 10 s Classification of Major Pediatric Brain Cancer Types with Picosecond Infrared Laser Mass Spectrometry.

Picosecond infrared laser mass spectrometry (PIRL-MS) is shown, through a retrospective patient tissue study, to differentiate medulloblastoma cancers from pilocytic astrocytoma and two molecular subtypes of ependymoma (PF-EPN-A, ST-EPN-RELA) using laser-extracted lipids profiled with PIRL-MS in 10 s of sampling and analysis time. The average sensitivity and specificity values for this classification, taking genomic profiling data as standard, were 96.41 and 99.54%, and this classification used many molecular features resolvable in 10 s PIRL-MS spectra. Data analysis and liquid chromatography coupled with tandem high-resolution mass spectrometry (LC-MS/MS) further allowed us to reduce the molecular feature list to only 18 metabolic lipid markers most strongly involved in this classification. The identified 'metabolite array' was comprised of a variety of phosphatidic and fatty acids, ceramides, and phosphatidylcholine/ethanolamine and could mediate the above-mentioned classification with average sensitivity and specificity values of 94.39 and 98.78%, respectively, at a 95% confidence in prediction probability threshold. Therefore, a rapid and accurate pathology classification of select pediatric brain cancer types from 10 s PIRL-MS analysis using known metabolic biomarkers can now be available to the neurosurgeon. Based on retrospective mining of 'survival' versus 'extent-of-resection' data, we further identified pediatric cancer types that may benefit from actionable 10 s PIRL-MS pathology feedback. In such cases, aggressiveness of the surgical resection can be optimized in a manner that is expected to benefit the patient's overall or progression-free survival. PIRL-MS is a promising tool to drive such personalized decision-making in the operating theater.

A case of solitary subependymal giant cell astrocytoma with histopathological anaplasia and TSC2 gene alteration.

We report a case of subependymal giant cell astrocytoma (SEGA) with anaplastic histological features in a 3-year-old girl. She had no clinical manifestations of tuberous sclerosis complex (TSC) and no relevant family history. A few cases have been reported in which patients with SEGA had no other clinical manifestations of TSC (solitary SEGA). Genetic analysis using a blood sample from the patient showed no germline alterations in TSC1 or TSC2 genes, while the tumor tissue exhibited loss of heterozygosity (LOH) in TSC2. SEGAs are benign, slowly growing tumors that rarely have significant mitotic activity. However, histopathological examination in the present case revealed high mitotic activity and necrosis besides the typical large plump cells arranged in sheets. This may be the first genetically proven case of a solitary SEGA with histopathological anaplastic features. In this report, we reviewed solitary SEGAs and histopathological malignancy in SEGA.

Persistent Primitive Hypoglossal Artery with Ipsilateral Symptomatic Carotid Artery Stenosis and Cerebral Aneurysm.

OBJECTIVE: Persistent primitive hypoglossal artery (PPHA) is a rare type of persistent carotid-basilar anastomosis sometimes associated with other vascular lesions. We treated an extremely rare case of PPHA with concomitant ipsilateral symptomatic cervical internal carotid artery (ICA) stenosis and unruptured aneurysm. CASE PRESENTATION: A 67-year-old woman visited our institution with acute onset of diplopia. Magnetic resonance imaging revealed multiple acute infarctions in the right anterior and posterior circulations. Digital subtraction angiography demonstrated the right PPHA concomitant with ipsilateral cervical ICA stenosis and an unruptured ICA aneurysm with maximum diameter of 8 mm. The multiple infarctions were considered to result from artery-to-artery embolism due to microthrombi from the ICA plaque passed along the PPHA, so carotid endarterectomy was performed as the first step with preoperative modified Rankin Scale (mRS) grade 1. During the operation, the patient had impaired ICA perfusion due to internal shunt catheter migration into the PPHA followed by acute infarction in the right hemisphere causing mild left hemiparesis. The patient was transferred to the rehabilitation hospital with mRS grade 3. After 3 months of rehabilitation, the patient recovered to mRS grade 1 and clipping surgery for the unruptured right ICA aneurysm was performed as the second step with uneventful postoperative course. CONCLUSION: The treatment strategy should be carefully considered depending on the specific blood circulation for such cases of PPHA with unique vasculature.

[Ruptured Aneurysms on the Cortical Segment of the Distal Posterior Inferior Cerebellar Artery:A Report of Two Cases and a Literature Review].

Two unusual cases of ruptured distal posterior inferior cerebellar artery(PICA)aneurysm on the cortical segment were successfully treated with open surgery. A 76-year-old woman presented with a Hunt and Kosnik(H&K)grade II Subarachnoid hemorrhage(SAH). CT showed a slight SAH in the cisterna magna and around the vermis, and fourth intraventricular hematoma. Cerebral angiography revealed an aneurysm on the cortical segment of the distal PICA. Intraoperative findings identified the aneurysm as fusiform. Trapping of the aneurysm was performed, and the indocyanine green angiography fiuding confirmed aneurysmal flow disappearance and good circulation in the cerebellar cortex. An 89-year-old woman presented with H&K grade II SAH. CT revealed a thick SAH in the posterior cranial fossa, and third to fourth intraventricular hematoma with hydrocephalus. Cerebral angiography revealed an aneurysm on the cortical segment of the distal PICA. Intraoperative findings showed that the aneurysm was fusiform. Trapping and resection of the aneurysm were performed. Thirteen previous cases of aneurysms on the cortical segment of the distal PICA have been reported. Distal PICA aneurysms apparently show rebleeding more frequently than do aneurysms at other locations, so immediate direct surgery is necessary to avoid rebleeding. After proximal ligation or trapping of the aneurysm, indocyanine green angiography is useful to determine the need for revascularization.

[Frontal Base Penetrating Brain Injury by a Gardening Scissors:A Case Report].

A 43-year-old woman accidentally fell from a 1.5-m height with gardening scissors, and the cutting edge of the scissors pierced into her skull base through the left nasal cavity. After she pulled the scissors out by herself, her consciousness immediately deteriorated. She was transferred to Juntendo University Shizuoka Hospital by an ambulance helicopter. Intracerebral hematoma in the right frontal lobe caused by the middle cerebral artery injury was detected using brain computed tomography. Emergent hematoma evacuation with decompressive craniectomy was performed. In this procedure, cerebrospinal fluid(CSF)leakage was repaired using a multi-layered flap technique, which placed both the free autologous dura mater and pedicled temporalis muscle flaps into the damaged skull base space. After the surgery, CSF drainage was managed to control both intracranial pressure and CSF leakage. Upon discussion, several clinical issues can be highlighted. First, the gardening scissors were pulled out by the patient herself. Second, the foreign material penetrating the intracranial space might have conferred a high infection risk. Finally, it might be difficult to repair the severe damage inflicted upon the skull base by the large gardening scissors. In conclusion, it was considered that favorable results were obtained by the emergent surgical intervention and by repairing the skull base through forming a multi-layered flap with a combination of free and pedicled tissues.

[Dissecting Aneurysm of the Distal Middle Cerebral Artery Formed the Out Pouch during Long-term Follow-up:A Case Report].

A 40-year-old man with a rare case of dissecting aneurysm of the distal middle cerebral artery(MCA, M2 segment)presented with ischemic stroke, manifesting as headache, nausea, and visual disorder. Computed tomography(CT)scan revealed cerebral infarction, and three-dimensional CT angiogram revealed stenotic change at the M2 segment. The patient was conservatively treated and remained neurologically stable. Ten months later, CT scan and magnetic resonance imaging(MRI)revealed outpouching of the M2 segment at the location of the initial stenosis. Angiogram revealed pearl and string sign at the M2 segment of the inferior trunk. The preoperative diagnosis was spontaneous dissecting aneurysm of the right distal MCA. The patient was treated with direct surgery for aneurysm resection and revascularization using the superficial temporal artery. The brain surface in contact with the dissecting aneurysm was colored xanthochromic, so minor bleeding from the dissecting aneurysm was highly suspected. Previously, 19 cases of dissecting aneurysm of the distal MCA have been reported. Distal dissecting aneurysms seem to rupture more frequently in the MCA than in the proximal segment. Long-term follow-up MRI and angiogram might be important, not only in the acute stage in patients with atypical caliber changes in the distal MCA. Immediate direct surgery is indicated to avoid hemorrhagic stroke if dilatation of the major trunk at the dissection is suspected.

Combination treatment with histone deacetylase and carbonic anhydrase 9 inhibitors shows therapeutic potential in experimental diffuse intrinsic pontine glioma.

Diffuse intrinsic pontine glioma (DIPG) remains a significant therapeutic challenge due to the lack of effective and safe treatment options. This study explores the potential of combining histone deacetylase (HDAC) and carbonic anhydrase 9 (CA9) inhibitors in treating DIPG. Analysis of RNA sequencing data and tumor tissue from patient samples for the expression of the carbonic anhydrase family and hypoxia signaling pathway activity revealed clinical relevance for targeting CA9 in DIPG. A synergy screen was conducted using CA9 inhibitor SLC-0111 and HDAC inhibitors panobinostat, vorinostat, entinostat, and pyroxamide. The combination of SLC-0111 and pyroxamide demonstrated the highest synergy and was selected for further analysis. Combining SLC-0111 and pyroxamide effectively inhibited DIPG cell proliferation, reduced cell migration and invasion potential, and enhanced histone acetylation, leading to decreased cell population in S Phase. Additionally, the combination therapy induced a greater reduction in intracellular pH than either agent alone. Data from this study suggest that the combination of SLC-0111 and pyroxamide holds promise for treating experimental DIPG, and further investigation of this combination therapy in preclinical models is warranted to evaluate its potential as a viable treatment for DIPG.

Cerebrospinal fluid rhinorrhea with meningoencephalocele related to Sternberg's canal: A report of two cases.

Background: Cerebrospinal fluid (CSF) rhinorrhea with meningoencephalocele (MEC) associated with Sternberg's canal is rare. We treated two such cases. Case Description: A 41-year-old man and a 35-year-old woman presented with CSF rhinorrhea and mild headache worsening with standing posture. Head computed tomography showed a defect close to the foramen rotundum in the lateral wall of the left sphenoid sinus in both cases. Head magnetic resonance (MR) imaging and MR cisternography revealed that brain parenchyma had herniated into the lateral sphenoid sinus through the defect of the middle cranial fossa. The intradural and extradural spaces and bone defect were sealed with fascia and fat through both intradural and extradural approaches. The MEC was cut away to prevent infection. CSF rhinorrhea completely stopped after the surgery. Conclusion: Our cases were characterized by empty sella, thinning of the dorsum sellae, and large arteriovenous malformations that suggest chronic intracranial hypertension. The possibility of Sternberg's canal in patients with CSF rhinorrhea with chronic intracranial hypertension should be considered. The cranial approach has the advantages of lower infection risk and the ability to close the defect with multilayer plasty under direct vision. The transcranial approach is still safe if performed by a skillful neurosurgeon.

Significance of endoscopic hematoma evacuation in elderly patients with spontaneous putaminal hemorrhage.

BACKGROUND: The efficacy of endoscopic surgery for spontaneous intracerebral hemorrhages (ICH) has been previously reported, but differences in the effect between early and late elderlies remain unclear. METHODS: Ninety-seven patients diagnosed with putaminal hemorrhage (age, ≥65 years; hematoma volume, ≥30 mL) were included in this retrospective analysis and separated into three treatment groups: craniotomy surgery (CR), endoscopic surgery (EN), and non-surgical (NS) groups. The patients were additionally subdivided into two groups according to age: patients aged 65-74 years ("early elderlies") and patients aged ≥75 years ("late elderlies"). Their clinical data and outcomes at discharge were compared using statistical analyses. RESULTS: The CR and the EN groups were associated with lower mortality rates (P < 0.001), lower modified Rankin Scale (mRS; P = 0.007), and lower National Institutes of Health Stroke Scale (NIHSS; P = 0.029) compared to the NS group. Early elderlies in the CR and EN groups with ICH scores of 3 also had significantly better outcomes (P = 0.001). The proportion of patients with mRS ≤ 4 was highest in the early elderlies of the EN group (P = 0.553). Although significant differences in the change of NIHSS scores between the early and late elderlies was not observed, significantly improved NIHSS scores were observed in the EN group compared to the NS group, even in the late elderlies (P = 0.037). CONCLUSION: The evacuation of deep-seated intracranial hematomas using the endoscope might improve functional outcomes and mortality, regardless of age.

MRI-guided focused ultrasound enhances drug delivery in experimental diffuse intrinsic pontine glioma.

Diffuse intrinsic pontine glioma (DIPG) is a surgically unresectable and devasting tumour in children. To date, there are no effective chemotherapeutics despite a myriad of clinical trials. The intact blood-brain barrier (BBB) is likely responsible for the limited clinical response to chemotherapy. MRI-guided focused ultrasound (MRgFUS) is a promising non-invasive method for treating CNS tumours. Moreover, MRgFUS allows for the temporary and repeated disruption of the BBB. Our group previously reported the feasibility of temporary BBB opening within the normal murine brainstem using MRgFUS following intravenous (IV) administration of microbubbles. In the current study, we set out to test the effectiveness of targeted chemotherapy when paired with MRgFUS in murine models of DIPG. Doxorubicin was selected from a drug screen consisting of conventional chemotherapeutics tested on patient-derived cell lines. We studied the RCAS/Tv-a model where RCAS-Cre, RCAS-PDGFB, and RCAS-H3.3K27M were used to drive tumourigenesis upon injection in the pons. We also used orthotopically injected SU-DIPG-6 and SU-DIPG-17 xenografts which demonstrated a diffusely infiltrative tumour growth pattern similar to human DIPG. In our study, SU-DIPG-17 xenografts were more representative of human DIPG with an intact BBB. Following IV administration of doxorubicin, MRgFUS-treated animals exhibited a 4-fold higher concentration of drug within the SU-DIPG-17 brainstem tumours compared to controls. Moreover, the volumetric tumour growth rate was significantly suppressed in MRgFUS-treated animals whose tumours also exhibited decreased Ki-67 expression. Herein, we provide evidence for the ability of MRgFUS to enhance drug delivery in a mouse model of DIPG. These data provide critical support for clinical trials investigating MRgFUS-mediated BBB opening, which may ameliorate DIPG chemotherapeutic approaches in children.

A rare presentation of a pediatric neurenteric cyst as an intra-axial pontine lesion: A case report with a 5-year follow-up.

BACKGROUND: Intracranial neurenteric cysts are rare, benign, and slow-growing tumors. However, we encountered a pediatric case that the cyst expansion occurred in a short period of time resulting in rapid deterioration of the patient's symptoms. CASE DESCRIPTION: A previously healthy 7-year-old girl had a week history of dysarthric speech and diplopia along with headaches. Her magnetic resonance images (MRI) showed an abnormal cystic mass in her brainstem. Her symptoms were deteriorated for 1 month and her second MRI revealed an enlargement of the cystic lesion. The tumor biopsy and cyst drainage were carried out and histopathological examination of the cyst wall showed columnar epithelium containing ciliated cells. The final diagnosis of her tumor was neurenteric cyst. CONCLUSION: We report a pediatric case of a neurenteric cyst in the brainstem, which expanded in a short period, and review this rare entity.