Two Pediatric Patients with Acute Acquired Comitant Esotropia as the First Symptom of Brainstem Tumor: A Case Report.

Introduction: Acute acquired comitant esotropia (AACE) is an acquired strabismus with uncrossed sudden-onset diplopia due to esodeviation, comitant esotropia without accommodation factor, or paretic eye movement. The diagnosis of AACE entails differentiation from incomitant esotropia caused by abnormalities in the central nervous system. We present 2 pediatric patients with AACE as the first symptom of brainstem tumor. Case Presentation: The 2 patients were aware of their diplopia and had no other neurological abnormalities. There were no special findings in the anterior segment, ocular media, or fundus. Esotropia with a difference of no more than 10Δ between distant and near fixations was observed. Eye movements were normal, and Hess red-green test under prism neutralization did not reveal abduction restriction. The presumed cause of AACE in both patients was excessive use of digital displays, and brain magnetic resonance imaging (MRI) was performed to confirm the absence of neurological abnormality. Using MRI, a definitive diagnosis of AACE was made based on comitant esotropia associated with diffuse median glioma and medullary pilocytic astrocytoma without abducens nerve palsy. Conclusion: Although the incidence of AACE caused by brainstem tumors may be low, it is necessary to perform head imaging to confirm etiology. Furthermore, Hess red-green test under prism neutralization is considered important for the differentiation of abducens nerve palsy.

Differentiation of astrocytoma between grades II and III using a combination of methionine positron emission tomography and magnetic resonance spectroscopy.

Objective: This study aimed to establish a method for differentiating between grades II and III astrocytomas using preoperative imaging. Methods: We retrospectively analyzed astrocytic tumors, including 18 grade II astrocytomas (isocitrate dehydrogenase (IDH)-mutant: IDH-wildtype = 8:10) and 56 grade III anaplastic astrocytomas (37:19). We recorded the maximum methionine (MET) uptake ratios (tumor-to-normal: T/N) on positron emission tomography (PET) and three MRS peak ratios: choline (Cho)/creatine (Cr), N-acetyl aspartate (NAA)/Cr, and Cho/NAA, between June 2015 and June 2020. We then evaluated the cut-off values to differentiate between grades II and III. We compared the grading results between contrast enhancement effects on MR and combinational diagnostic methods (CDM) on a scatter chart using the cutoff values of the T/N ratio and MRS parameters. Results: The IDH-mutant group showed significant differences in the Cho/NAA ratio between grades II and III using univariate analysis; however, multiple regression analysis results negated this. The IDH-wildtype group showed no significant differences between the groups. Contrast enhancement effects also showed no significant differences in IDH status. Accordingly, regardless of the IDH status, no statistically independent factors differentiated between grades II and III. However, CDMs showed higher sensitivity and negative predictive value in distinguishing them than MRI contrast examinations for both IDH statuses. We demonstrated a significantly higher diagnostic rate of grade III than of grade II with CDM, which was more striking in the IDH-mutant group than in the wild-type group. Conclusions: CDM could be valuable in differentiating between grade II and III astrocytic tumors.

[Suprasellar Tumor-Craniotomy].

Surgical procedures for pediatric suprasellar tumors include craniotomy and nasal surgery. Craniotomies are increasingly performed with a microscope, exoscope, and endoscope, while nasal surgery is performed mainly with endoscopes. In some cases, craniotomy and nasal surgery are performed together. This article describes craniotomy. Due to its large surgical field, craniotomy is often chosen for large tumors in the suprasellar region, tumors located above the optic chiasm and optic nerve, tumors extending laterally, and hypervascularized tumors. It is the surgical technique of choice for many neurosurgeons because they are familiar with it. Craniotomies include bilateral frontal and frontotemporal craniotomies. The interhemispheric and subfrontal approaches involve bilateral frontal craniotomy, pterional approach, orbitozygomatic approach, subtemporal approach using temporal-occipital craniotomy, and transpetrosal transtentorial approach using temporal-occipital-suboccipital craniotomy. The approach was selected based on the direction of tumor extension and relationship between the tumor and optic nerve, optic chiasm, and blood vessels. This paper describes the frequently used interhemispheric and pterional approaches based on our experience.

A common deletion at BAK1 reduces enhancer activity and confers risk of intracranial germ cell tumors.

Intracranial germ cell tumors (IGCTs) are rare brain neoplasms that mainly occur in children and adolescents with a particularly high incidence in East Asian populations. Here, we conduct a genome-wide association study (GWAS) of 133 patients with IGCTs and 762 controls of Japanese ancestry. A common 4-bp deletion polymorphism in an enhancer adjacent to BAK1 is significantly associated with the disease risk (rs3831846; P = 2.4 × 10-9, odds ratio = 2.46 [95% CI: 1.83-3.31], minor allele frequency = 0.43). Rs3831846 is in strong linkage disequilibrium with a testicular GCTs susceptibility variant rs210138. In-vitro reporter assays reveal rs3831846 to be a functional variant attenuating the enhancer activity, suggesting its contribution to IGCTs predisposition through altering BAK1 expression. Risk alleles of testicular GCTs derived from the European GWAS show significant positive correlations in the effect sizes with the Japanese IGCTs GWAS (P = 1.3 × 10-4, Spearman's ρ = 0.48). These results suggest the shared genetic susceptibility of GCTs beyond ethnicity and primary sites.

Perianeurysmal cyst formation in the brainstem after coil embolization: illustrative case.

BACKGROUND: Perianeurysmal cysts in the brainstem after endovascular coil embolization are rare, and their underlying mechanism remains unclear. The authors reported a case of a postcoiling perianeurysmal cyst that developed 6 years after endovascular coil embolization for a ruptured aneurysm and reviewed the related literature. OBSERVATIONS: A 77-year-old woman had a history of subarachnoid hemorrhage 6 years earlier. The ruptured large left vertebral artery-posterior inferior cerebellar artery aneurysm was treated with endovascular coil embolization. Two years later, the aneurysm regrew and perianeurysmal brainstem edema was detected on magnetic resonance imaging (MRI); stent-assisted coil embolization combined with low-flow bypass was performed. Follow-up MRI showed that the perianeurysmal edema gradually transformed into a perianeurysmal cyst over the next 3 years. Finally, the perianeurysmal cyst caused gait disturbance with ataxia, and the patient received cyst puncture. After surgery, the symptom was immediately improved. LESSONS: The authors reported, for the first time, postcoiling of perianeurysmal cyst formation treated by cyst puncture. If perianeurysmal edema is detected after endovascular coil embolization, especially for large aneurysms, it is necessary to consider progression to cyst formation and follow up over time. In addition, cyst puncture is effective, depending on the symptoms and the lesion.

A rare pediatric case of McCune-Albright syndrome with acute visual disturbance: Case report.

RATIONALE: McCune-Albright syndrome (MAS) is a rare disorder characterized by clinical findings, which includes fibrous dysplasia (FD). FD is a benign tumor that leads to increased rates of bone fracture. In some MAS cases with FD, facial deformities, severe pain, and orbital neuropathies are complicated. Aneurysmal bone cyst (ABC) is a benign bone tumor and rare complication of FD. PATIENT CONCERNS: A 9-year-old boy was admitted to our hospital because of acute visual disturbance. DIAGNOSIS AND INTERVENTIONS: The patient was clinically diagnosed as ABC complicated with MAS, and he underwent surgery. OUTCOMES: After the surgery, his sight became normal. Recurrence of ABC and visual disturbance was not observed in 3 years. Genetic analysis of a tissue sample from the ABC lesion by next-generation sequencing revealed a somatic activating GNAS mutation. LESSONS: To the best of our knowledge, this is the first case report of MAS causing optic neuropathy complicated with ABC. ABC complicated with MAS is extremely rare, but it should be considered as a possible diagnosis in patients with acute visual loss and facial swelling. In addition, our case had OAS, which is an uncommon syndrome and a rare complication in ABC with MAS, and rapid decompression of the ABC was effective in improving the patient's eyesight.

Prediction of nuclide accumulation spread based on the volume of enhancing MRI lesion in glioblastoma patients.

BACKGROUND: 11C-methionine-PET (MET) and Thallium-201 chloride-SPECT (TL) are useful for predictive proliferation ability and tumor invasion range identification in glioma patients, however they are not always possible in any hospital or country. Our study aimed to assess whether the range of MET and Tl accumulation could be predicted from the contrast-enhanced lesions in Gadolinium (Gd)-T1 weighted MR image (Gd-MRI) in glioblastoma multiforme (GBM) patients. METHODS: In 25 cases, the MET-Area, TL-Area, O-Area where MET and TL overlap, and all accumulation area (AA-Area) were measured in the same axial cross section as the Gd enhanced maximum area (Gd-Area). This tracing operation was repeated with all axial fusion slices, and each volume was also measured (Gd-V, MET-V, TL-V, O-V, AA-V). RESULTS: The maximum accumulation distance of MET and TL beyond the Gd-Area was limited to within 30 mm, 35 mm, respectively. Significant positive correlations were showed in all combinations with Gd-Area: MET-Area (r=0.851, p<0.0001), TL-Area (r=0.955, p<0.0001), O-Area (r=0.935, p<0.0001) and AA-Area (r=0.893, p<0.0001), respectively. All combinations with Gd-V showed significant positive correlation: MET-V (r=0.867, p<0.0001), TL-V (r=0.952, p<0.0001), O-V (r=0.935, p<0.0001) and AA-V (r=0.897, p<0.0001), respectively. CONCLUSIONS: Approximate tumor volume Gd-V can be calculated using the formula A * B * C / 2, where A, B, and C represent the dimensions of Gd-enhanced lesion in 3 axes perpendicular to each other. The nuclide accumulation predictive table created using the obtained linear approximation functions can be used to predict the average tumor invasion range from the Gd-V without preoperative nuclear examinations.

A Sporadic Pediatric Case of Huge Intracranial Supratentorial Desmoid-type Fibromatosis.

Desmoid-type fibromatosis (DTF) is a rare locally aggressive soft tissue neoplasm without metastatic potential. Here, we report a very rare sporadic case of an intracranial supratentorial extradural DTF measuring 82 mm in a 1-year-old girl, that recurred twice following surgery over the course of 16 months, requiring two other surgeries. In three surgeries, we resected a huge tumor with the dura which was thought to be tumor origin and removed this tumor infiltrated the frontal skull base by drilling widely. Furthermore, we treated the tumor invading the bone flap using liquid nitrogen for 20 minutes, and subsequently used it to perform a cranioplasty. This tumor has not recurred for past 8 months. DTF invading the skull base is prone to recurrence, and liquid nitrogen treatment is considered to be effective in pediatric patients, who need cranioplasty with tumor-infiltrating autologous bone flaps.

Endoscopic third ventriculostomy for hydrocephalus in a patient with achondroplasia: a case report and literature review.

Hydrocephalus, a complication of achondroplasia, requires treatment when it is symptomatic. Hydrocephalus associated with achondroplasia is often treated with ventriculoperitoneal shunting, and endoscopic third ventriculostomy (ETV) is rarely performed in these patients. Here, we report the case of an 18-month-old boy with achondroplasia and progressive hydrocephalus who underwent ETV. He had a family history of achondroplasia and was diagnosed with achondroplasia at birth. Magnetic resonance imaging (MRI) at the age of 1 month showed no hydrocephalus. At the age of 15 months, he was admitted to our hospital due to increased head circumference. He had developmental delays, and MRI showed hydrocephalus with ballooning of the third ventricle. The ETV success score was 80 points; therefore, we performed ETV. Postoperatively, the progression of head circumference increase was controlled. The ventricular size remained unchanged on MRI at 13 months after surgery. Recently, an association between non-communicating hydrocephalus and achondroplasia has been reported. Depending on age and imaging findings, ETV may be effective in some patients with achondroplasia with hydrocephalus.

Diagnosis and treatment of primary central nervous system lymphoma with the primary lesion in the hypothalamus: a case report.

BACKGROUND: Primary central nervous system lymphoma is a rare extra-nodal lymphoma of the central nervous system. Primary central nervous system lymphoma lesions usually appear in the vicinity of the ventricle, and there are few reports of primary central nervous system lymphoma with hypothalamic-pituitary lesions. CASE PRESENTATION: We treated a 56-year-old male with primary central nervous system lymphoma with the primary lesion in the hypothalamus, which was found by magnetic resonance imaging after sudden onset of endocrinological abnormalities. Initially, he was hospitalized to our department for hyponatremia. Endocrinological examination in conjunction with head magnetic resonance imaging and endoscopic biopsy revealed hypothalamic hypopituitarism and tertiary hypoadrenocorticism caused by a rapidly growing, diffuse large B-cell lymphoma in the hypothalamus. Remission of the tumor was achieved by high-dose methotrexate with whole brain radiotherapy, and some of the hormone responses were normalized. CONCLUSIONS: While primary central nervous system lymphoma is rare, it is important to note that hypopituitarism can result and that the endocrinological abnormalities can be partially restored by its remission.

A pediatric case of anaplastic astrocytoma with a gliomatosis cerebri; the growth pattern and changes in serum VEGF-121 levels after bevacizumab treatment.

Gliomatosis cerebri (GC) is a rare diffusely infiltrating glial neoplasm that carries a poor prognosis. Because tumors are undetectable in most patients at early-stage of the onset, a useful diagnostic method is expected. We compared serum vascular endothelial growth factor (VEGF)-121 levels in patients with GC or glioblastoma and controls. VEGF-121 levels were significantly higher in one patient with GC and patients with glioblastoma than in controls. VEGF-121 levels decreased in a patient with GC after bevacizumab-based therapy. Thus, VEGF-121 may be useful for diagnosing GC, its disease-monitoring and understanding its etiology.

Proinflammatory Cytokine Secretion in a Patient With Recurrent Neuroblastoma Related to the Onset of Malignancy-associated Hemophagocytic Lymphohistiocytosis.

The onset of malignancy-associated hemophagocytic lymphohistiocytosis (M-HLH) may be associated with the secretion of proinflammatory cytokines from malignant cells. We here report a patient with recurrent neuroblastoma who developed hemophagocytic lymphohistiocytosis after surgery for brain metastases and relapsed after chemotherapy. The neuroblastoma cells in the recurrent tumor were positive for tumor necrosis factor-α and interleukin-6, whereas the primary site was negative. The secretion of proinflammatory cytokines from neuroblastoma cells may have been related to the pathogenesis of M-HLH in our patients. We should pay attention to possible development of M-HLH when treating advanced neuroblastoma.

Brain Abscess Presenting as Prolonged Headache in a Patient with Amyotrophic Lateral Sclerosis under Mechanical Ventilation.

A 57-year-old woman with amyotrophic lateral sclerosis (ALS) receiving mechanical ventilation developed intractable right temporal headache. She was diagnosed with brain abscess secondary to chronic suppurative otitis media. In this case, the otitis media was caused by nasopharyngeal reflux associated with eustachian tube muscle weakness and a supine position. In addition, ALS patients under mechanical ventilation have a limited ability to convey their pain. Their complaints are often overlooked because many physicians do not know that pain is common in ALS. Physicians should recognize brain abscess as a severe complication of ALS and listen to the complaints of these patients.

[A Patient with Progressive Multifocal Leukoencephalopathy Who Developed Bálint Syndrome Improved by Combination Therapy Using Mefloquine and Mirtazapine].

We describe a 62-year-old man who developed subacute visual loss after cord blood stem cell transplantation for malignant lymphoma. Brain magnetic resonance imaging (MRI) showed bilateral hyperintense lesions in the occipital and parietal lobes. A diagnosis of progressive multifocal encephalopathy (PML) was established following brain biopsy and detection of JC virus (JCV) deoxyribonucleic acid (DNA) in the cerebrospinal fluid (CSF). He developed optic ataxia and visual inattention, and was then diagnosed as having Bálint syndrome. After he was treated with mefloquine and mirtazapine, his Bálint syndrome and, MRI findings improved and the copy number of JCV DNA in the CSF decreased. In summary, we demonstrate that patient with PML may develop Bálint syndrome and that combination therapy using mefloquine and mirtazapine may be an effective treatment. (Received August 23, 2018; Accepted November 29, 2018; Published March 1, 2019).

Fatal Progression of Gorham-Stout Disease with Skull Base Osteomyelitis and Lateral Medullary Syndrome.

Gorham-Stout disease (GSD) is a rare condition in which spontaneous, progressive resorption of bone occurs. There are no previous reports of patients with fatal progression of GSD with skull base osteomyelitis (SBO) and lateral medullary syndrome (LMS). We present the case of a 27-year-old man diagnosed with GSD with involvement of the maxillofacial bones and skull base. The patient developed SBO; LMS resulted from progressive osteolysis, and the patient died of associated brainstem stroke. Careful follow-up with special emphasis on the early detection of intracranial complications is critical in patients presenting with progressive GSD with involvement of the skull base.

Efficacy, Reliability, and Safety of Completely Autologous Fibrin Glue in Neurosurgical Procedures: Single-Center Retrospective Large-Number Case Study.

OBJECTIVE: Commercially available fibrin glue (Com-FG), which is used commonly worldwide, is produced with pooled human plasma from multiple donors. However, it has added bovine aprotinin, which involves the risk of infection, allogenic immunity, and allergic reactions. We evaluate the efficacy, reliability, and safety of completely autologous fibrin glue (CAFG). METHODS: From August 2014 to February 2016, prospective data were collected and analyzed from 153 patients. CAFG was prepared with the CryoSeal System using autologous blood and was applied during neurosurgical procedures. Using CAFG-soaked oxidized regenerated cellulose and/or polyglycolic acid sheets, we performed a pinpoint hemostasis, transposed the offending vessels in a microvascular decompression, and covered the dural incision to prevent cerebrospinal fluid leakage. RESULTS: The CryoSeal System had generated up to a mean of 4.51 mL (range, 3.0-8.4 mL) of CAFG from 400 mL autologous blood. Com-FG products were not used in our procedures. Only 6 patients required an additional allogeneic blood transfusion. The hemostatic effective rate was 96.1% (147 of 153 patients). Only 1 patient who received transsphenoidal surgery for a pituitary adenoma presented with the complication of delayed postoperative cerebrospinal fluid leakage (0.65%). No patient developed allergic reactions or systemic complications associated with the use of CAFG. CONCLUSIONS: CAFG effectively provides hemostatic, adhesive, and safety performance. The timing and three-dimensional shape of CAFG-soaked oxidized regenerated cellulose and/or polyglycolic acid sheets solidification can be controlled with slow fibrin formation. The cost to prepare CAFG is similar compared with Com-FG products, and it can therefore be easily used at most institutions.

Pathological analysis of the surgical margins of resected glioblastomas excised using photodynamic visualization with both 5-aminolevulinic acid and fluorescein sodium.

During glioma resection, 5-aminolevulinic acid (5-ALA) and fluorescein sodium (Fl-Na) are used for photodynamic tumor visualization. The objective of this study was to evaluate the pathological findings of the boundary zone between the tumor and adjacent normal brain in glioblastoma patients undergoing simultaneous double staining with 5-ALA and Fl-Na during surgery. Eight patients received 5-ALA (20 mg/kg orally) before the induction of general anesthesia, and Fl-Na (20 mg/kg) was administered intravenously before the dural incision was performed. The tumor bulk was removed under the guidance of Fl-Na staining alone using conventional white light. Subsequently, residual tumor was removed under the guidance of both fluorescent agents within functionally safe limits until both were visibly undetectable. Twenty specimens exhibiting different staining intensities of both agents were obtained. The vessel index (VI) was calculated from CD31 immunohistochemistry (IHC) samples. Boundary zone tumor cells were detected by IHC for olig2, and were expressed as the olig2 index (OLI). The VI was significantly higher in Fl-Na-positive areas than in Fl-Na-negative areas (p = 0.0005). In contrast, the OLI was significantly higher in 5-ALA-positive areas than in 5-ALA-negative areas (p = 0.0149). 5-ALA-positive/Fl-Na negative areas were observed in 7 patients. These findings indicate that Fl-Na accumulates in areas with a disrupted blood-brain barrier, and that 5-ALA fluorescence is dependent on tumor cell protoporphyrin IX metabolism. In conclusion, 5-ALA was better for detecting tumor cells in the boundary zone than was Fl-Na. Of note, tumor cells existed outside the fluorescence-stained boundaries of both agents.

Dynamic study of methionine positron emission tomography in patients with glioblastoma with oligodendroglial components.

Anaplastic oligoastrocytoma (AOA) with necrosis is classified as glioblastoma (GBM) with oligodendroglioma component (GBMO), according to the 2007 World Health Organization classification. The prognosis of GBMO remains controversial because definitive diagnostic criteria regarding the percentage of the oligodendroglial components (OC) in the GBM do not exist. We previously reported dynamic methionine (MET) positron emission tomography (PET) in patients with these tumors. A significant decrease in the MET signal was seen in oligodendrocytic tumors, in contrast to a significant MET increase in GBMs. In this study, we analyzed the dynamic MET PET signal in four patients with primary (n = 2) and secondary (n = 2) GBMOs. Static PET scanning was performed in three consecutive phases. Both cases of primary GBMOs and one case of secondary GBMO presented with a gradual decrease in MET PET signal over the consecutive phases. In contrast, the remaining case of secondary GBMO presented with a pattern of slight increase. It is likely that the dynamic change of MET in patients with GBMO resemble those in patients with oligodendroglial tumor, however, further studies are needed to confirm them. We discuss the mechanisms from a viewpoint of pathological findings.

Bevacizumab treatment leads to observable morphological and metabolic changes in brain radiation necrosis.

We investigated morphological and metabolic changes of radiation necrosis (RN) of the brain following bevacizumab (BEV) treatment by using neuroimaging. Nine patients with symptomatic RN, who had already been treated with radiation therapy for malignant brain tumors (6 glioblastomas, 1 anaplastic oligodendroglioma, and 2 metastatic brain tumors), were enrolled in this prospective clinical study. RN diagnosis was neuroradiologically determined with Gd-enhanced MRI and 11C-methionine positron emission tomography (MET-PET). RN clinical and radiological changes in MRI, magnetic resonance spectroscopy (MRS) and PET were assessed following BEV therapy. Karnofsky performance status scores improved in seven patients (77.8 %). Both volumes of the Gd-enhanced area and FLAIR-high area from MRI decreased in all patients after BEV therapy and the mean size reduction rates of the lesions were 80.0 and 65.0 %, respectively. MRS, which was performed in three patients, showed a significant reduction in Cho/Cr ratio after BEV therapy. Lesion/normal tissue (L/N) ratios in MET- and 11C-choline positron emission tomography (CHO-PET) decreased in 8 (89 %) and 9 patients (100 %), respectively, and the mean L/N ratio reduction rates were 24.4 and 60.7 %, respectively. BEV-related adverse effects of grade 1 or 2 (anemia, neutropenia and lymphocytopenia) occurred in three patients. These results demonstrated that BEV therapy improved RN both clinically and radiologically. BEV therapeutic mechanisms on RN have been suggested to be related not only to the effect on vascular permeability reduction by repairing the blood-brain barrier, but also to the effect on suppression of tissue biological activity, such as immunoreactions and inflammation.