Bilateral choroid plexus resection in a 9p hexasomy/tetrasomy mosaic patient.

Previous reports have shown that a gain of the chromosome 9 short arm (9p) is associated with choroid plexus hyperplasia (CPH). Furthermore, CPH can lead to communicating hydrocephalus; however, no cases of CPH with 9p gain requiring choroid plexus resection have been reported. Here, we describe the first case in which a 9p hexasomy/tetrasomy mosaic patient required choroid plexus resection for hydrocephalus. This finding suggested that the 9p copy number is correlated with CPH severity.

Two Cases of Atypical Teratoid/Rhabdoid Tumor in the Spinal Cord: Loss of SMARCB1 in a Child and Loss of SMARCA4 in an Adult.

We compare two cases of primary spinal atypical teratoid/rhabdoid tumor (AT/RT), which rarely occurs in adults marked by SMARCA4 inactivation, and SMARCB1 inactivation for pediatric cases. AT/RT represents a highly malignant neoplasm comprising poorly differentiated constituents and rhabdoid cells, with SMARCB1(INI1) or infrequently SMARCA4 (BRG1) inactivation. These tumors are predominantly found in children but are rare in adults. While AT/RT can arise anywhere in the central nervous system, spinal cord localization is comparatively scarce. Despite mutation or loss of SMARCB1 at the 22q11.2 locus serving as the genetic hallmark of AT/RTs, infrequent cases of SMARCA4 inactivation with intact SMARCB1 protein expression are significant. We present each case of primary spinal tumors in a child and an adult, showing loss of the SMARCB1 and SMARCA4 proteins, respectively. Both tumors met the AT/RT diagnostic criteria. The histopathology demonstrated the presence of rhabdoid cells in both cases. Diagnosing primary spinal AT/RT with SMARCB1 protein loss remains a challenge. Nevertheless, the presence of SMARCB1 positivity alone must be noted to be insufficient to exclude the possibility of AT/RT diagnosis. In cases in which the diagnosis of AT/RT is highly suspected clinically, additional testing is warranted, including SMARCA4 analysis.

Analysis of False-negative Findings of the Incomparable Accuracy and Swiftness of Flow Cytometric Diagnosis of Primary Central Nervous System Lymphoma.

Primary central nervous system lymphoma (PCNSL), a relatively rare brain tumor, bears a dire prognosis. On occasion, the rapid progression of the tumor makes immediate diagnosis and initiation of therapy imperative. To achieve swift diagnosis, we adopt flow cytometry (FCM) in addition to conventional histopathology. This study aimed to reveal the utility of FCM diagnosis for PCNSL and the cause of false-negative results of FCM diagnosis. We investigated 33 patients with suspected PCNSL on neuroradiological findings and received both FCM and histological diagnosis. The patients' electronic medical records were investigated, and histological findings, results of FCM, and other clinical data were evaluated. Overall, 27 patients (14 males and 13 females) were diagnosed with PCNSL by histological confirmation. The median age at diagnosis was 68 years. FCM analysis showed lymphoma pattern in 24 cases; however, FCM results did not show lymphoma pattern (sensitivity: 88.9%, specificity: 100%) in the other three lymphoma cases (FCM discordant: FCM-D) and six nonlymphomatous tumor cases. Analysis of FCM-D cases showed the infiltration of T lymphocytes or astrocytes into the tumor tissue, indicating tumor microenvironmental reaction; it is assumed that these reactions deceived FCM diagnosis. The survival of FCM-D patients was superior to FCM concordant counterpart, although the difference was not significant (p = 0.459). The diagnosis of PCNSL by FCM is rapid and highly reliable. Some FCM-D cases are PCNSLs with strong tumor microenvironmental reactions.

Bacterial meningitis caused by nontraumatic cerebrospinal fluid rhinorrhea with aqueductal stenosis: A case report.

Background: Nontraumatic cerebrospinal fluid (CSF) rhinorrhea associated with aqueductal stenosis is rare. The resulting CSF leakage may cause bacterial meningitis, and appropriately timed surgical treatment should be considered. Case Description: A 28-year-old woman with obstructive hydrocephalus secondary to aqueductal stenosis presented with intermittent nasal discharge. CSF rhinorrhea was suspected, but she refused surgery. During the course of conservative treatment, she developed meningitis. Exacerbation of hydrocephalus and CSF rhinorrhea was suspected, and the patient underwent endoscopic third ventriculostomy after recovery from meningitis. Postoperatively, ventricular size decreased and CSF leakage completely resolved. There was no recurrence of hydrocephalus or rhinorrhea. Conclusion: Patients with intermittent CSF rhinorrhea due to exacerbation of hydrocephalus are at high risk for bacterial meningitis. Appropriately timed surgical treatment results in a favorable outcome.

Early rebleeding of a foramen magnum dural arteriovenous fistula: A case report and review of the literature.

Foramen magnum dural arteriovenous fistula (FM-DAVF) is a subset of craniocervical junction arteriovenous fistulas. We report a rare case of FM-DAVF with early rebleeding and review the literature. A 50-year-old man experienced 3 episodes of intracranial bleeding from a vessel malformation in the acute stage. We identified an FM-DAVF, supplied by multiple feeding arteries (eg, left ascending pharyngeal artery) that drained into the straight sinus and left superior petrosal sinus. The draining vein had venous varices. We performed transarterial feeder embolization and surgical disconnection of the DAVF. Early rebleeding of FM-DAVF is rare. High-risk patients require risk assessment and appropriate treatment as soon as possible in the acute stage.

Inhibition of Gli2 suppresses tumorigenicity in glioblastoma stem cells derived from a de novo murine brain cancer model.

The prognosis of glioblastoma remains poor despite intensive research efforts. Glioblastoma stem cells (GSCs) contribute to tumorigenesis, invasive capacity, and therapy resistance. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), a stem cell marker, is involved in the maintenance of GSCs, although the properties of Lgr5-positive GSCs remain unclear. Here, the Sleeping-Beauty transposon-induced glioblastoma model was used in Lgr5-GFP knock-in mice identify GFP-positive cells in neurosphere cultures from mouse glioblastoma tissues. Global gene expression analysis showed that Gli2 was highly expressed in GFP-positive GSCs. Gli2 knockdown using lentiviral-mediated shRNA downregulated Hedgehog-related and Wnt signaling pathway-related genes, including Lgr5; suppressed tumor cell proliferation and invasion capacity; and induced apoptosis. Pharmacological Gli inhibition with GANT61 suppressed tumor cell proliferation. Silencing Gli2 suppressed the tumorigenicity of GSCs in an orthotopic transplantation model in vivo. These findings suggest that Gli2 affects the Hedgehog and Wnt pathways and plays an important role in GSC maintenance, suggesting Gli2 as a therapeutic target for glioblastoma treatment.

Activated leukocyte cell adhesion molecule expression correlates with the WNT subgroup in medulloblastoma and is involved in regulating tumor cell proliferation and invasion.

Cluster of differentiation (CD) 166 or activated leukocyte cell adhesion molecule (ALCAM) is a transmembrane molecule known to be an intercellular adhesion factor. The expression and function of ALCAM in medulloblastoma (MB), a pediatric brain tumor with highly advanced molecular genetics, remains unclear. Therefore, this study aimed to clarify the significance and functional role of ALCAM expression in MB. ALCAM expression in 45 patients with MB was evaluated by immunohistochemical analysis of formalin-fixed paraffin-embedded clinical specimens and the relationship between ALCAM expression and pathological type/molecular subgroup, such as WNT, SHH, Group 3, and Group 4, was examined. Eight ALCAM positive (18%), seven partially positive (16%), and 30 negative (67%) cases were detected. All seven cases of the WNT molecular subgroup were ALCAM positive and ALCAM expression strongly correlated with this subgroup (P < 0.0001). In addition, functional studies using MB cell lines revealed ALCAM expression affected proliferation and migration as a positive regulator in vitro. However, ALCAM silencing did not affect survival or the formation of leptomeningeal dissemination in an orthotopic mouse model, but did induce a malignant phenotype with increased tumor cell invasion at the dissemination sites (P = 0.0029). In conclusion, our results revealed that ALCAM exhibited highly specific expression in the WNT subgroup of MB. Furthermore, we demonstrated that the cell kinetics of MB cell lines can be altered by the expression of ALCAM.

Aplastic or Twig-Like Middle Cerebral Artery Presenting with Intracerebral Hemorrhage During Pregnancy: Report of Two Cases.

BACKGROUND: An aplastic or twig-like middle cerebral artery (Ap/T-MCA) is a rare congenital anomaly that can present with both ischemic and hemorrhagic stroke. The etiology of this pathology has remained unclear. Here, we report 2 cases of intracerebral hemorrhage (ICH) owing to an Ap/T-MCA in pregnant patients. CASE DESCRIPTION: In both patients, cerebral angiography revealed a steno-occlusive lesion and an abnormal arterial network on the unilateral middle cerebral artery. One patient was treated conservatively for a putaminal hemorrhage, and a cesarean section was performed uneventfully 6 months after onset of the ICH. The other patient underwent a craniotomy for evacuation of the lobar hemorrhage. Subsequently, a cesarean section was performed uneventfully. Both patients gradually recovered without significant disabilities. CONCLUSIONS: An Ap/T-MCA is a rare congenital anomaly and is a potential cause of ICH for pregnant patients. A cesarean section is a useful option for pregnant patients with this condition.

Unusual Presentations of Pediatric Skull Hemangiomas: Report of Two Cases.

BACKGROUND: Intraosseous hemangioma is a rare bone tumor, accounting for 0.7%-1.0% of all bone tumors. It can occur at any age, but only 9% of cases are younger than 10 years old. Although this tumor is usually slow-growing and clinically silent, we experienced 2 pediatric patients undergoing surgery for skull hemangioma who presented with uncommon clinical manifestations. CASE DECRIPTION: Case 1 was a 9-year-old boy who presented with sudden onset of headache and was referred to our hospital. Radiologic images revealed an osteolytic oval lesion in the right parietal bone and acute subdural hemorrhage in the right cerebral hemisphere. The right parietal lesion was removed surgically. The lesion was found to have grown into the dura and to be adherent to the pia matter. The removed lesion was histologically confirmed to be a hemangioma. Case 2 was an 8-year-old girl who was referred to our hospital with an elastic mass that had been slowly enlarging for 7 years. Radiologic images revealed an osteolytic oval lesion in the right parietal bone. Surgical removal was thus planned. The lesion was found to be attached to the dura, and we removed the lesion with the surrounding bone and attached dura. Histologic examination confirmed the lesion to be a hemangioma. CONCLUSIONS: Although skull hemangiomas show clinical heterogeneity, surgical removal is usually diagnostic and leads to good patient outcomes. On occasion, however, this tumor causes secondary changes in the dura, such that dural incision and dural plasty should be planned in advance of lesion removal.

A case of optic-nerve hypoplasia and anterior segment abnormality associated with facial cleft.

INTRODUCTION: The incidence of facial cleft is rare and ranges between 1.43 and 4.85 per 100,000 births. To date, there have been few reports of detailed ophthalmologic examinations performed in cases of facial cleft. Here, we report a case of optic-nerve hypoplasia and anterior segment abnormality associated with facial cleft. CASE REPORT: A 9-day-old female infant was delivered by cesarian section at 34 weeks of gestational age (the second baby of twins) and weighed 2,276 g upon presentation. She had a facial cleft and ectrodactyly at birth. Right eye-dominant blepharophimosis was obvious. Examination of the right eye revealed inferior corneal opacity with vascularization, downward corectopia, and optic-nerve hypoplasia. The corneal diameter was 8 mm in both eyes, and tonometry by use of a Tono-Pen(®) XL (Reichert Technologies, Depew, NY, USA) handheld applanation tonometer revealed that her intraocular pressure was 11-22 mmHg (Oculus Dexter) and 8 mmHg (Oculus Sinister). B-mode echo revealed no differences in axial length between her right and left eyes. When she was 15-16 months old, we attempted to examine her eyes before she underwent plastic surgery under general anesthesia. She had a small optic disc in both eyes and the right-eye disc was tilted. After undergoing canthotomy, gonioscopy and ultrasound biomicroscopy revealed that almost all directions were open except for the peripheral anterior synechia. Since magnetic resonance imaging revealed ventriculomegaly associated with an interhemispheric cyst at birth, a ventriculoperitoneal shunt was inserted at 12 days of age. At 25 months of age, her condition suddenly deteriorated due to occlusion of the ventricular shunt catheter, and she died 5 days later. In this patient, amniotic band syndrome was presumed to be the primary cause due to the clinical findings. CONCLUSION: We experienced a case of optic-nerve hypoplasia and anterior segment abnormality that occurred with facial cleft. The cause of these abnormalities is unclear, yet amniotic band syndrome is a possible candidate.

Sudden death in a case of megalencephaly capillary malformation associated with a de novo mutation in AKT3.

INTRODUCTION: Megalencephaly capillary malformation (MCAP) is a syndrome involving brain overgrowth, characterized by megalencephaly, capillary malformations, asymmetric growth, polymicrogyria, polydactyly, and syndactyly. Cerebellar tonsillar herniation (CTH) and ventriculomegaly are also observed in over half the patients with this syndrome. Early sudden death has been reported in MCAP, but its causes and the surgical strategies for its prevention remain unclear. CASE REPORT: Here, we report on a patient with MCAP who died suddenly at 5 months of age. He presented with progressive macrocephaly and hypotonia. MRI performed at 4 months of age showed tight posterior fossa, bilateral perisylvian polymicrogyria, enlargement of the straight sinus, and a thickened corpus callosum. However, since the patient did not exhibit capillary malformation, polydactyly, or syndactyly, a definitive diagnosis of MCAP could not be made. He died suddenly while asleep at home 1 month later. The sudden death of MCAP patients was previously attributed to CTH, convulsion, or arrhythmia. In this case, progressive cerebellar enlargement appeared to be the underlying cause. After the patient's death, using his preserved DNA, a missense mutation in the AKT3 gene was identified. Vakt murine thymoma viral oncogene homologue (AKT) is a serine-threonine kinase that functions in the mammalian target of rapamycin (mTOR) pathway and plays an important role in cell proliferation. CONCLUSION: Accurate early diagnosis, including imaging and genetic analyses, and the recognition and treatment of critical conditions are required to prevent the sudden death of patients with MCAP.

[Retrograde cavernous sinus air embolism after central venous catheter removal].

Air embolism is a rare, but occasionally fatal complication of peripheral and central venous catheterization. We present a case of an 89-year-old female, who had a central venous catheter placed in her right jugular vein during the perioperative period for right femoral subtrochanteric fracture. On the day following her operation, level of consciousness worsened a few minutes after the catheter was removed. CT scan showed air bubbles in bilateral cavernous sinuses and brachiocephalic vein. Administration of 100% oxygen was started, and she regained consciousness a few hours later, finally air bubbles disappeared on a CT scan performed 10 hours after onset. Air embolism should be taken into consideration when treating venous catheters, and appropriate O2 administration and radiological examinations must be performed immediately if level of consciousness or vital signs deteriorate.

[Endoscopic findings in chronic subdural hematoma].

On the genesis of chronic subdural hematoma (CSH), it is one of the possible explanations that a head injury triggers uncertain cause off for the formation of the hematoma membrane, where the bleeding occurs to form and enlarge the hematoma. Although some reports on the staging classification based on computed tomography (CT) findings are available the natural course or history of the hematoma formation is not yet known. As previously reported, we have been using an endoscopically guided method in which a drainage tube is placed in the most frontal area of the cavity so as to evacuate the residual air efficiently. In this study, we analyzed the endoscopic findings in hematoma cavities and compared them with the clinical data, focusing on the post-trauma interval and recurrence of the hematoma. Between January 1999 and October 2000, we had an opportunity to observe the inner aspect of 60 hematomas in 48 patients. A trabecular structure was found in 39 hematoma cavities (65%), whereas apparent clot formation was observed in 18 cavities (30%). Septum formation leading to a multi-loculated hematoma was observed in 10 cavities (17%). Twenty-six patients with 32 hematomas with the obvious history of head injury were classified into 4 groups according to the post-traumatic interval to the surgery, which are stage I; less than 30 days, stage II; 31 to 60 days, stage III; 61 to 90 days and stage IV; more than 91 days. Clot formation and a trabecular structure were frequently seen in stages II and III. Clot formation was statistically and significantly seen in the recurrent group. The results suggest that CSHs increase in size in stages II and III, when clot formation and a trabecular structure are frequently observed. Endoscopic observation of hematomas may assist to know hematomas, and clot formation may be a warning of hematoma recurrence.